Parapapillary choroidal microvasculature dropout in eyes with primary open-angle glaucoma.

The purpose of this study was to evaluate how various parameters are related to microvasculature dropout (MvD) area measured using optical coherence tomography angiography (OCTA). We measured the area of MvD in 55 patients with primary open-angle glaucoma (POAG). Using OCTA, MvD area and peripapillary choroidal atrophy (PPA) area were assessed in a 4.5 mm × 4.5 mm region. The following were examined: circumpapillary nerve fiber layer (cpRNFL) thickness, optic disc area, optic disc cupping area, optic disc rim area, Humphrey Field Analyzer (HFA) 24/10-2 mean deviation (MD), and pattern standard deviation (PSD). The relationship between MvD area and each parameter was evaluated using Spearman's rank correlation coefficient analysis. Mean MvD area and PPA area were 0.18 ± 0.17 mm2 and 1.13 ± 0.72 mm2, respectively. MvD area was significantly correlated with optic disc rim area (p = 0.0017), cpRNFL (p = 0.0027), HFA 24/10-2 MD, and PSD (p < 0.001). In eyes with POAG, MvD area indicates the severity of glaucoma, which might be associated with structural changes in the peripapillary vasculature around the optic disc.

Relationship between Inter-Eye Asymmetries in Corneal Hysteresis and Visual Field Severity in Patients with Primary Open-Angle Glaucoma.

This study investigated the influence of asymmetric corneal hysteresis (CH) on asymmetric visual field impairment between right and left eyes in patients with primary open-angle glaucoma (POAG) without a history of intraocular surgery. CH, corneal resistance factor (CRF), and corneal compensated intraocular pressure (IOPcc) were measured using the Ocular Response Analyzer. Differences between the eyes (right eye-left eye: DIFRL) and CH-based and in target parameters (higher CH eye-lower CH eye: DIFCH) were calculated in the same patient. In 242 phakic eyes of 121 patients, older age (p < 0.001), lower CH (p = 0.001), and lower CRF (p = 0.007) were significantly associated with worse standard automated perimetry (SAP) 24-2 mean deviation (MD). The DIFsRL in axial length (p = 0.003), IOPcc (p = 0.028), and CH (p = 0.001) were significantly associated with the DIFRL in SAP24-2 MD, but not in central corneal thickness (CCT), Goldmann applanation tonometry (GAT) measurement, and CRF. When dividing the patients into two groups based on the median of the CH DIFsCH (0.46), the DIFsCH in CRF (p < 0.001), IOPcc (p < 0.001), CCT (p = 0.004), SAP24-2 MD (p < 0.001), and SAP10-2 MD (p = 0.010) were significantly different between the groups. Large inter-eye asymmetry in CH is an important explanatory factor for disease worsening in patients with POAG.

Estimation of the central 10-degree visual field using en-face images obtained by optical coherence tomography.

PURPOSE: To estimate the central 10-degree visual field of glaucoma patients using en-face images obtained by optical coherence tomography (OCT), and to examine its usefulness. PATIENTS AND METHODS: Thirty-eight eyes of 38 patients with primary open angle glaucoma were examined. En-face images were obtained by swept-source OCT (SS-OCT). Nerve fiber bundles (NFBs) on en-face images at points corresponding to Humphrey Field Analyzer (HFA) 10-2 locations were identified with retinal ganglion cell displacement. Estimated visual fields were created based on the presence/absence of NFBs and compared to actual HFA10-2 data. κ coefficients were calculated between probability plots of visual fields and NFBs in en-face images. RESULTS: Actual HFA10-2 data and estimated visual fields based on en-face images were well matched: when the test points of <5%, <2%, and <1% of the probability plot in total deviation (TD) and pattern deviation (PD) of HFA were defined as points with visual field defects, the κ coefficients were 0.58, 0.64, and 0.66 in TD, respectively, and 0.68, 0.69, and 0.67 in PD. In eyes with spherical equivalent ≥ -6 diopters, κ coefficients for <5%, <2%, and <1% were 0.58, 0.62, and 0.63 in TD and 0.66, 0.67, and 0.65 in PD, whereas for the myopic group with spherical equivalent < -6 diopters, the values were 0.58, 0.69, and 0.71 in TD and 0.72, 0.71, and 0.71 in PD, respectively. There was no statistically significant difference in κ coefficients between highly myopic eyes and eyes that were not highly myopic. CONCLUSIONS: NFB defects in en-face images were correlated with HFA10-2 data. Using en-face images obtained by OCT, the central 10-degree visual field was estimated, and a high degree of concordance with actual HFA10-2 data was obtained. This method may be useful for detecting functional abnormalities based on structural abnormalities.

Foveal Avascular Zone Measurement Via Optical Coherence Tomography Angiography and its Relationship With the Visual Field in Eyes With Open-angle Glaucoma.

PRECIS: The foveal avascular zone (FAZ) in optical coherence tomography angiography is significantly correlated with retinal inner layer thickness, Humphrey field analyzer (HFA) 10-2 sensitivity threshold, and mean deviation (MD) value in open-angle glaucoma patients. PURPOSE: The purpose of this study was to measure the FAZ area using optical coherence tomography angiography and investigate its relationship with retinal inner layer thickness and visual field defects in eyes with open-angle glaucoma. PARTICIPANTS AND METHODS: A total of 52 eyes with open-angle glaucoma from 52 patients. FAZ area was measured using optical coherence tomography angiography in angio-macula mode. Thicknesses of retinal nerve fiber layer (RNFL), ganglion cell layer plus inner plexiform layer (GCL+IPL), and ganglion cell complex (GCC) were determined using a 7 mm×7 mm macular (V) map via 3D-OCT. Correlations of FAZ area with sensitivity threshold measurements, foveal threshold (FT), and MD value in the HFA10-2 visual field were analyzed for each inner retinal layer. RESULTS: FAZ area was 0.26±0.07 mm; overall mean thicknesses were 19.14±6.55 µm (RNFL), 57.34±5.93 µm (GCL+IPL), and 75.87±10.96 µm (GCC); mean FT was 35.23±3.15 dB, and sensitivity threshold was 20.81±7.22 dB in the HFA10-2 visual field. FAZ area was significantly correlated with the thickness of individual retinal layers in the entire field (RNFL, P<0.001; GCL+IPL, P<0.001; GCC, P<0.001), sensitivity threshold (P=0.01), FT (P<0.001), and MD value (P=0.011). CONCLUSION: FAZ area was significantly negatively correlated with retinal inner layer thickness, sensitivity threshold, FT, and MD value in the HFA10-2 visual field.

The stress response gene ATF3 is a direct target of the Wnt/ß-catenin pathway and inhibits the invasion and migration of HCT116 human colorectal cancer cells.

Aberrant Wnt/ß-catenin signaling is implicated in tumorigenesis and the progression of human colorectal cancers, and mutations in the components of the Wnt/ß-catenin signaling pathway are observed in the majority of patients. Therefore, extensive studies on the Wnt signaling pathway and its target genes are crucial to understand the molecular events of tumorigenesis and develop an efficacious therapy. In this study, we showed that the stress response gene ATF3 is transcriptionally activated by the binding of ß-catenin and TCF4 to the redundant TCF4 site at the proximal promoter region of the ATF3 gene, indicating that ATF3 is a direct target of the Wnt/ß-catenin pathway. The loss of function or overexpression studies showed that ATF3 inhibited the migration or invasion of HCT116 cells. The expression of some MMP and TIMP genes and the ratio of MMP2/9 to TIMP3/4 mRNAs was differentially regulated by ATF3. Therefore, though ATF3 is activated downstream of the Wnt/ß-catenin pathway, it acts as a negative regulator of the migration and invasion of HCT116 human colon cancer cells exhibiting aberrant Wnt/ß-catenin activity. ATF3 is a candidate biomarker and target for human colorectal cancer treatment and prevention.

Optical coherence tomography angiography of the peripapillary capillaries in primary open-angle and normal-tension glaucoma.

OBJECTIVES: To evaluate the vascular architecture of the radial peripapillary capillaries (RPCs) and its relation with visual function in patients with open-angle glaucoma (OAG) and normal-tension glaucoma using spectral-domain optical coherence tomography (SD-OCT) angiography. SUBJECTS AND METHODS: Clear OCT angiography images of blood vessels in the optic disc and peripapillary retina were obtained from 52 patients (52 eyes) aged 55.42±10.64 (range 28-72) years with primary OAG. The mean spherical equivalent was -3.19±2.31 diopters, and the mean deviation (MD) of the central 24/30-2 threshold test using the Humphrey Field Analyzer (HFA) was -10.47±7.99 dB. The correlations between the disappearance angle of the RPCs on OTC images, flow density (FD) and the circumpapillary retinal nerve fiber layer (cpRNFL) thickness, the angle of retinal nerve fiber layer (RNFL) defect, the MD and pattern standard deviation (PSD) values of the HFA central 24/30-2 threshold test using the Swedish interactive thresholding algorithm, the sensitivity threshold, age, corneal thickness, and refractive value were analyzed. In addition, the correlation between FD and the cpRNFL thickness was analyzed at FD measurement points. RESULTS: FD was significantly correlated with cpRNFL thickness, PSD value, MD value, and sensitivity threshold, whereas the disappearance angle of the RPCs was significantly correlated with the angle of the RNFL defect (P<0.001), MD value (P<0.01), and sensitivity threshold (P<0.01). There was a negative correlation between FD and age (P<0.05). The Pearson correlation coefficient of FD and cpRNFL thickness in the area surrounding the optic disc revealed the most significant correlation in the inferior visual field (r = 0.851, P<0.001), followed by the superior visual field (r = 0.803, P<0.001) and then the temporal visual field (r = 0.653, P<0.001). CONCLUSION: SD-OCT angiography enabled thorough observation of the RPCs. FD and the disappearance angle of the RPCs were significantly and independently correlated with glaucoma-related functional and morphological changes in the optic nerve, suggesting that these two factors are novel functional and morphological indicators of visual defects due to glaucoma.

Evaluating Silent Reading Performance with an Eye Tracking System in Patients with Glaucoma.

OBJECTIVE: To investigate the relationship between silent reading performance and visual field defects in patients with glaucoma using an eye tracking system. METHODS: Fifty glaucoma patients (Group G; mean age, 52.2 years, standard deviation: 11.4 years) and 20 normal controls (Group N; mean age, 46.9 years; standard deviation: 17.2 years) were included in the study. All participants in Group G had early to advanced glaucomatous visual field defects but better than 20/20 visual acuity in both eyes. Participants silently read Japanese articles written horizontally while the eye tracking system monitored and calculated reading duration per 100 characters, number of fixations per 100 characters, and mean fixation duration, which were compared with mean deviation and visual field index values from Humphrey visual field testing (24-2 and 10-2 Swedish interactive threshold algorithm standard) of the right versus left eye and the better versus worse eye. RESULTS: There was a statistically significant difference between Groups G and N in mean fixation duration (G, 233.4 msec; N, 215.7 msec; P = 0.010). Within Group G, significant correlations were observed between reading duration and 24-2 right mean deviation (rs = -0.280, P = 0.049), 24-2 right visual field index (rs = -0.306, P = 0.030), 24-2 worse visual field index (rs = -0.304, P = 0.032), and 10-2 worse mean deviation (rs = -0.326, P = 0.025). Significant correlations were observed between mean fixation duration and 10-2 left mean deviation (rs = -0.294, P = 0.045) and 10-2 worse mean deviation (rs = -0.306, P = 0.037), respectively. CONCLUSIONS: The severity of visual field defects may influence some aspects of reading performance. At least concerning silent reading, the visual field of the worse eye is an essential element of smoothness of reading.

Strategy for designing selective α-l-rhamnosidase inhibitors: Synthesis and biological evaluation of l-DMDP cyclic isothioureas.

This study shows that the cyclization of l-DMDP thioureas to bicyclic l-DMDP isothioureas improved α-l-rhamnosidase inhibition which was further enhanced by increasing the length of the alkyl chain. The addition of a long alkyl chain, such as decyl or dodecyl, to the nitrogen led to the production of highly potent inhibitors of α-l-rhamnosidase; it also caused broad inhibition spectrum against ß-glucosidase and ß-galactosidase. In contrast, the corresponding N-benzyl-l-DMDP cyclic isothioureas display selective inhibition of α-l-rhamnosidase; 3',4'-dichlorobenzyl-l-DMDP cyclic isothiourea (3r) was found to display the most potent and selective inhibition of α-l-rhamnosidase, with IC50 value of 0.22µM, about 46-fold better than the positive control 5-epi-deoxyrhamnojirimycin (5-epi-DRJ; IC50=10µM) and occupied the active-site of this enzyme (Ki=0.11µM). Bicyclic isothioureas of ido-l-DMDP did not inhibit α-l-rhamnosidase. These new mimics of l-rhamnose may affect other enzymes associated with the biochemistry of rhamnose including enzymes involved in progression of tuberculosis.