Validating Variational Bayes Linear Regression Method With Multi-Central Datasets.

PurposeTo validate the prediction accuracy of variational Bayes linear regression (VBLR) with two datasets external to the training dataset.MethodThe training dataset consisted of 7268 eyes of 4278 subjects from the University of Tokyo Hospital. The Japanese Archive of Multicentral Databases in Glaucoma (JAMDIG) dataset consisted of 271 eyes of 177 patients, and the Diagnostic Innovations in Glaucoma Study (DIGS) dataset includes 248 eyes of 173 patients, which were used for validation. Prediction accuracy was compared between the VBLR and ordinary least squared linear regression (OLSLR). First, OLSLR and VBLR were carried out using total deviation (TD) values at each of the 52 test points from the second to fourth visual fields (VFs) (VF2-4) to 2nd to 10th VF (VF2-10) of each patient in JAMDIG and DIGS datasets, and the TD values of the 11th VF test were predicted every time. The predictive accuracy of each method was compared through the root mean squared error (RMSE) statistic.ResultsOLSLR RMSEs with the JAMDIG and DIGS datasets were between 31 and 4.3 dB, and between 19.5 and 3.9 dB. On the other hand, VBLR RMSEs with JAMDIG and DIGS datasets were between 5.0 and 3.7, and between 4.6 and 3.6 dB. There was statistically significant difference between VBLR and OLSLR for both datasets at every series (VF2-4 to VF2-10) (P < 0.01 for all tests). However, there was no statistically significant difference in VBLR RMSEs between JAMDIG and DIGS datasets at any series of VFs (VF2-2 to VF2-10) (P > 0.05).ConclusionsVBLR outperformed OLSLR to predict future VF progression, and the VBLR has a potential to be a helpful tool at clinical settings

Contribution of Intragenic DNA Methylation in Mouse Gametic DNA Methylomes to Establish Oocyte-Specific Heritable Marks

Genome-wide dynamic changes in DNA methylation are indispensable for germline development and genomic imprinting in mammals. Here, we report single-base resolution DNA methylome and transcriptome maps of mouse germ cells, generated using whole-genome shotgun bisulfite sequencing and cDNA sequencing (mRNA-seq). Oocyte genomes showed a significant positive correlation between mRNA transcript levels and methylation of the transcribed region. Sperm genomes had nearly complete coverage of methylation, except in the CpG-rich regions, and showed a significant negative correlation between gene expression and promoter methylation. Thus, these methylome maps revealed that oocytes and sperms are widely different in the extent and distribution of DNA methylation. Furthermore, a comparison of oocyte and sperm methylomes identified more than 1,600 CpG islands differentially methylated in oocytes and sperm (germline differentially methylated regions, gDMRs), in addition to the known imprinting control regions (ICRs). About half of these differentially methylated DNA sequences appear to be at least partially resistant to the global DNA demethylation that occurs during preimplantation development. In the absence of Dnmt3L, neither methylation of most oocyte-methylated gDMRs nor intragenic methylation was observed. There was also genome-wide hypomethylation, and partial methylation at particular retrotransposons, while maintaining global gene expression, in oocytes. Along with the identification of the many Dnmt3L-dependent gDMRs at intragenic regions, the present results suggest that oocyte methylation can be divided into 2 types: Dnmt3L-dependent methylation, which is required for maternal methylation imprinting, and Dnmt3L-independent methylation, which might be essential for endogenous retroviral DNA silencing. The present data provide entirely new perspectives on the evaluation of epigenetic markers in germline cells

Influence of corneal power on circumpapillary retinal nerve fiber layer and optic nerve head measurements by spectral-domain optical coherence tomography

AIM: To evaluate the influence of corneal power on circumpapillary retinal nerve fiber layer (cpRNFL) and optic nerve head (ONH) measurements by spectral-domain optical coherence tomography (SD-OCT). METHODS: Twenty-five eyes of 25 healthy participants (mean age 23.6±3.6y) were imaged by SD-OCT using horizontal raster scans. Disposable soft contact lenses of different powers (from −11 to +5 diopters including 0 diopter) were worn to induce 2-diopter changes in corneal power. Differences in the cpRNFL and ONH measurements per diopter of change in corneal power were analyzed. RESULTS: As corneal power increased by 1 diopter, total and quadrant cpRNFL thicknesses, except for the nasal sector, decreased by −0.19 to −0.32 μm (P<0.01). Furthermore, the disc, cup, and rim areas decreased by −0.017, −0.007, and −0.015 mm2, respectively (P<0.001); the cup and rim volumes decreased by −0.0013 and −0.006 mm3, respectively (P<0.01); and the vertical and horizontal disc diameters decreased by −0.006 and −0.007 mm, respectively (P<0.001). CONCLUSION: For more precise OCT imaging, the ocular magnification should be corrected by considering both the axial length and corneal power. However, the effect of corneal power changes on cpRNFL thickness and ONH topography are small when compare with those of the axial length

Determination of axial length requiring adjustment of measured circumpapillary retinal nerve fiber layer thickness for ocular magnification.

To determine the axial length requiring adjustment of measured circumpapillary retinal nerve fiber layer (cpRNFL) thickness to account for ocular magnification during spectral-domain optical coherence tomography (SD-OCT).In this prospective study, 148 eyes of 148 healthy student volunteers were imaged by two examiners using three-dimensional SD-OCT. In 54 randomly selected eyes, total cpRNFL thickness was measured with and without adjustment for ocular magnification to establish intra-examiner and inter-examiner measurement error. The 148 eyes were then divided into three groups according to the error values: control group (difference in the corrected and uncorrected total cpRNFL thickness was within the measurement error range), thinner group (the corrected total cpRNFL thickness was less than the uncorrected one), and thicker group (the corrected total cpRNFL thickness was more than the uncorrected one). The cutoff values of axial length between the control and the other groups were calculated by receiver operating characteristic analysis.Measurement error ranged from 4.2 to 5.3 µm; the threshold value was defined as 5.3 µm. The cutoff values of axial length between the thinner and the control groups and between the control and the thicker groups were 23.60 (area under the curve [AUC] = 0.959) and 25.55 (AUC = 0.944) mm, respectively.Axial lengths shorter than 23.60 mm and longer than 25.55 mm require adjustment of measured cpRNFL thickness to account for ocular magnification during SD-OCT.UMIN Clinical Trials Registry (http://www.umin.ac.jp/) under unique trial number UMIN000013248 (date of registration: 02/24/2014)

Smaller Fixation Target Size Is Associated with More Stable Fixation and Less Variance in Threshold Sensitivity.

The aims of this randomized observational case control study were to quantify fixation behavior during standard automated perimetry (SAP) with different fixation targets and to evaluate the relationship between fixation behavior and threshold variability at each test point in healthy young participants experienced with perimetry. SAP was performed on the right eyes of 29 participants using the Octopus 900 perimeter, program 32, dynamic strategy. The fixation targets of Point, Cross, and Ring were used for SAP. Fixation behavior was recorded using a wearable eye-tracking glass. All participants underwent SAP twice with each fixation target in a random fashion. Fixation behavior was quantified by calculating the bivariate contour ellipse area (BCEA) and the frequency of deviation from the fixation target. The BCEAs (deg2) of Point, Cross, and Ring targets were 1.11, 1.46, and 2.02, respectively. In all cases, BCEA increased significantly with increasing fixation target size (p < 0.05). The logarithmic value of BCEA demonstrated the same tendency (p < 0.05). A positive correlation was identified between fixation behavior and threshold variability for the Point and Cross targets (ρ = 0.413-0.534, p < 0.05). Fixation behavior increased with increasing fixation target size. Moreover, a larger fixation behavior tended to be associated with a higher threshold variability. A small fixation target is recommended during the visual field test

Evaluation of refractive correction for standard automated perimetry in eyes wearing multifocal contact lenses

AIM: To evaluate the refractive correction for standard automated perimetry (SAP) in eyes with refractive multifocal contact lenses (CL) in healthy young participants. METHODS: Twenty-nine eyes of 29 participants were included. Accommodation was paralyzed in all participants with 1% cyclopentolate hydrochloride. SAP was performed using the Humphrey SITA-standard 24-2 and 10-2 protocol under three refractive conditions: monofocal CL corrected for near distance (baseline); multifocal CL corrected for distance (mCL-D); and mCL-D corrected for near vision using a spectacle lens (mCL-N). Primary outcome measures were the foveal threshold, mean deviation (MD), and pattern standard deviation (PSD). RESULTS: The foveal threshold of mCL-N with both the 24-2 and 10-2 protocols significantly decreased by 2.2-2.5 dB CONCLUSION: Despite the induced mydriasis and the optical design of the multifocal lens used in this study, our results indicated that, when the dome-shaped visual field test is performed with eyes with large pupils and wearing refractive multifocal CLs, distance correction without additional near correction is to be recommended

Comparison of Humphrey Field Analyzer and imo visual field test results in patients with glaucoma and pseudo-fixation loss.

The aim of this cross-sectional study was to evaluate the results of a visual field (VF) test for patients with glaucoma and pseudo-fixation loss. These patients exhibit fixation loss (FL) rates >20% with the Humphrey Field Analyzer (HFA); however, actual fixation stabilizes when a head-mounted perimeter (imo) is used. This device is able to adjust the stimulus presentation point by tracking eye movements. We subjected 54 eyes of 54 patients with glaucoma and pseudo-FL to the HFA 30-2 or 24-2 Swedish Interactive Threshold Algorithm -Standard protocol. All patients also underwent the imo 30-2 or 24-2 Ambient Interactive Zipper Estimated Sequential Testing protocol after HFA measurement. We compared HFA and imo reliability indices [including false-positive (FP) responses, false-negative (FN) responses, and FL rate], global indices [including mean deviation (MD), visual field index (VFI), and pattern standard deviation (PSD)], and retinal sensitivity for each test point. There were no significant differences in MD, VFI, and PSD between HFA and imo, and these measures were strongly correlated (r > 0.96, p < 0.01). There were no significant differences in FP and FN between both devices, while FL measured with HFA (27.5%) was significantly reduced when measured with imo (13.2%) (p < 0.01). There was no correlation in FL and FN between both devices, and a weak correlation for FP (r = 0.29, p = 0.04). At each test point, retinal sensitivity averaged 1.7 dB higher with HFA, compared with imo (p < 0.01). There was no significant variability in global indices in patients with pseudo-FL. The FP response rate might have influenced measures of FL in patients with glaucoma and pseudo-FL

Effect of nifekalant on life-threatening ventricular arrhythmias in patients with cardiopulmonary resuscitation or during the perioperative state

Background: Nifekalant is a unique class III anti-arrhythmic agent with a strong effect on prolonging the myocardial refractoriness, but its clinical effect is still unclear. In this study, we evaluated the effect of nifekalant on life-threatening ventricular arrhythmias and compared the clinical background between the effective and non-effective patients in order to clarify the clinical factors which may have an influence on the efficacy of nifekalant. Methods: The study population consisted of 47 consecutive patients who underwent nifekalant administration for life-threatening ventricular arrhythmias (VT/VF). Their clinical characteristics and ECG parameters were retrospectively compared between patients with and without an effective result with the nifekalant administration. Results: Nifekalant was effective for refractory VT/VF in 26/47 patients. There was no significant difference in the age, gender or left ventricular ejection fraction, but the incidence of ischemic heart disease was higher in the effective group (17/26) than non-effective group (9/21, p = 0.004). The incidence of in-hospital events was higher in the effective group than non-effective group (20/26 vs 10/21, p = 0.037). A significant prolongation in the QTc interval was observed in all patients and the degree of QTc prolongation was greater in the effective group than in the non-effective group (0.46 ± 0.04 vs 0.43 ± 0.02 sec1/2, p = 0.026). Conclusion: Nifekalant was effective in 55% of the patients for refractory VT/VF. It was considered that nifekalant was more effective for patients with ischemic heart disease, during the perioperative period or in those experiencing in-hospital events. The prolongation of the QTc interval might also be useful as an index for the efficacy of nifekelant administration

Degree of loss in the tissue thickness, microvascular density, specific perimetry and standard perimetry in early glaucoma

Objective To identify the degree of loss of the circumpapillary retinal nerve fibre layer (cpRNFL), the layer from the macular RNFL to the inner plexiform layer (mGCL++), circumpapillary (cpVD) and macular vascular density (mVD), Pulsar perimetry and standard perimetry in early glaucoma.Methods In this cross-sectional study, one eye from each of 96 healthy controls and 90 eyes with open-angle glaucoma were measured with cpRNFL, mGCL++, cpVD, mVD, Pulsar perimetry with Octopus P32 test (Pulsar) and standard perimetry with Humphrey field analyser 24-2 test (HFA). For direct comparison, all parameters were converted to relative change values adjusted in both their dynamic range and age-corrected normal value.Results The degree of loss in mGCL++ (−24.7%) and cpRNFL (−25.8%) was greater than that in mVD (−17.3%), cpVD (−14.9%), Pulsar (−10.1%) and HFA (−5.9%) (each p&lt;0.01); the degree of loss in mVD and cpVD was greater than that in Pulsar and HFA (each p&lt;0.01); and the degree of loss in Pulsar was greater than that in HFA (p&lt;0.01). The discrimination ability between glaucomatous and healthy eyes (area under the curve) was higher for mGCL++ (0.90) and cpRNFL (0.93) than for mVD (0.78), cpVD (0.78), Pulsar (0.78) and HFA (0.79).Conclusion The degree of loss of cpRNFL and mGCL++ thickness preceded by approximately 7%–10% and 15%–20% compared with the micro-VD and visual fields in early glaucoma, respectively.Trial registration number UMIN Clinical Trials Registry (http://www.umin.ac.jp/; R000046076 UMIN000040372)

Effects of Different Levels of Intraocular Stray Light on Kinetic Perimetry Findings

<div><p>Purpose</p><p>To evaluate the effect of different levels of intraocular stray light on kinetic perimetry findings.</p><p>Methods</p><p>Twenty-five eyes of 25 healthy young participants were examined by automated kinetic perimetry (Octopus 900) using Goldmann stimuli III4e, I4e, I3e, I2e, and I1e. Each stimulus was presented with a velocity of 3°/s at 24 meridians with 15° intervals. Four levels of intraocular stray light were induced using non-white opacity filter (WOF) filters and WOFs applied to the clear plastic eye covers of the participants. The visual acuity, pupil diameter, isopter area, and kinetic sensitivity of each meridian were analyzed for each WOF density.</p><p>Results</p><p>Visual acuity deteriorated with increasing WOF densities (p < 0.01). With a visual acuity of 0.1 LogMAR units, the isopter areas for III4e, I4e, I3e, I2e, and I1e decreased by -32.7 degree² (-0.2%), -255.7 degree² (-2.6%), -381.2 degree² (-6.2%), -314.8 degree² (-12.8%), and -59.2 degree² (-15.2%), respectively; kinetic sensitivity for those stimuli decreased by -0.1 degree (-0.1%), -0.8 degree (-1.4%), -1.6 degree (-3.7%), -2.7 degree (-9.7%), and -1.7 degree (-16.2%), respectively. The pupil diameter with each WOF density was not significantly different.</p><p>Conclusion</p><p>Kinetic perimetry measurements with a high-intensity stimulus (i.e., III4e) were unaffected by intraocular stray light. In contrast, measurements with the I4e, I3e, I2e, and I1e stimuli, especially I2e and I1e, were affected. Changes in the shape of the isopter resulting from opacity must be monitored, especially in cases of smaller and lower-intensity stimuli.</p></div