Topographic distribution and phenotypic heterogeneity of Schlemm's canal endothelium in human donor eyes.

Endothelium phenotype is known to be closely associated with flow shear stress. This study is to determine the topographic distribution of endothelial cells and the phenotype of different quadrants and regions of Schlemm's canal using human donor eyes. This study infers differences in flow dynamics based on cell shape and intracellular structure. The Schlemm's canal from 15 human donor eyes were either perfusion labelled using silver stain or dissected for float labeling with Phalloidin to enable visualization of endothelial cell border and intracellular structure. Data were acquired for endothelial cells from the outer and inner wall of Schlemm's canal and grouped according to quadrant of origin. Measurements included endothelial cell length, width, area, and aspect ratio and compared between quadrants. Endothelial cells are mostly spindle-shape and the cell size on the outer wall are larger and longer than those from the inner wall. Significant differences in endothelial cell size and shape were seen in different quadrants. The endothelial cells have varied shapes and orientations close to large ostia in the outer wall and remarkably long endothelial cells were found in the walls of collector channels. F-actin aggregation was found at all endothelial cell borders, and inside some of the endothelial cytoplasm. The presence of various spindle shapes, significant phenotype heterogeneity and F-actin aggregation of endothelial cells indicates aqueous humor flow likely creates variations in shear stress within Schlemm's canal. Further investigation of the relationship between the phenotype heterogeneity and hydrodynamics of aqueous flow may help us understand the mechanisms of outflow resistance changes in glaucoma.

Prospective 12-month outcomes of combined iStent inject implantation and phacoemulsification in Asian eyes with normal tension glaucoma.

BACKGROUND: Glaucoma is the leading cause of irreversible blindness. Normal tension glaucoma (NTG) is a subset of open-angle glaucoma, demonstrating glaucomatous optic nerve damage in the absence of raised intraocular pressure (IOP). NTG is more prevalent in Asian populations. While generally slow-progressing, NTG may be associated with significant central visual field loss. In recent years, minimally invasive glaucoma surgery has been added to the armamentarium of glaucoma surgery. This prospective study aims to evaluate 12-month surgical outcomes of combined iStent inject (Glaukos Corporation, Laguna Hills, CA) implantation and phacoemulsification in Asian eyes with NTG. METHODS: This is a prospective, single-centre case series of 30 eyes followed up until 12 months after surgery. Outcome measures included IOP, number of glaucoma medications, best-corrected visual acuity (BCVA) and intra and postoperative complications. RESULTS: Mean age of subjects was 73.1 ± 6.3 years. Majority were ethnic Chinese (n = 27, 90%). Baseline medicated mean IOP was 13.8 ± 2.4 mmHg and mean number of glaucoma medications was 1.3 ± 0.7. Mean Humphrey visual field mean deviation was - 13.7 ± 7.6. The mean IOP reduction at all timepoints from postoperative month (POM) 3 onwards was statistically significant (all P < 0.05), with mean reduction of 1.2 mmHg (95% CI: 0.1-2.2, P = 0.037) by POM12. There was statistically significant reduction in mean number of medications from postoperative day (POD) 1 onwards (all P < 0.05), with mean decrease of 1.0 medication (95% CI: 0.9-1.1, P < 0.001) by POM12. By POM12, 25 (83.3%) eyes were medication-free. Three (10%) eyes had stent occlusion by iris requiring laser iridoplasty. One eye had gross hyphema which resolved on conservative management before POM1. Mean BCVA improved from the baseline 0.3 ± 0.3 logMAR to 0.1 ± 0.1 logMAR postoperatively (P < 0.001). There were no major adverse or sight-threatening events. No eyes required further glaucoma surgery during the 12-month follow-up period. CONCLUSION: Asian eyes with NTG which underwent combined iStent inject implantation and phacoemulsification demonstrated a significant and sustained reduction in IOP and glaucoma medications, up to 12 months postoperatively.

Automatic Glaucoma Detection from Stereo Fundus Images.

This paper proposes a new method for automatic detection of glaucoma from stereo pair of fundus images. The basis for detecting glaucoma is using the optic cup-to-disc area ratio, where the surface area of the optic cup is segmented from the disparity map estimated from the stereo fundus image pair. More specifically, we first estimate the disparity map from the stereo image pair. Then, the optic disc is segmented from one of the stereo image. Based upon the location of the optic disc, we perform an active contour segmentation on the disparity map to segment the optic cup. Thereafter, we can compute the optic cup-to-disc area ratio by dividing the area (i.e. the total number of pixels) of the segmented optic cup region to that of the segmented optic disc region. Our experimental results using the available test dataset shows the efficacy of our proposed approach.

Optical Coherence Tomography Angiography of Optic Disc and Macula Vessel Density in Glaucoma and Healthy Eyes.

AIM: To study the microvascular density of the macular and optic nerve head in healthy and glaucoma subjects using optical coherence tomography angiography. METHODOLOGY: We performed a cross-sectional cohort study on healthy subjects and patients with glaucoma. The AngioVue Enhanced Microvascular Imaging System was used to capture the optic nerve head and macula images during one visit. En face segment images of the macular and optic disc were studied in layers. Microvascular density of the optic nerve head and macula were quantified by the number of pixels measured by a novel in-house developed software. Areas under the receiver operating characteristic curves (AUROC) were used to determine the accuracy of differentiating between glaucoma and healthy subjects. RESULTS: A total of 24 (32 eyes) glaucoma subjects (57.5±9.5-y old) and 29 (58 eyes) age-matched controls (51.17±13.5-y old) were recruited. Optic disc and macula scans were performed showing a greater mean vessel density (VD) in healthy compared with glaucoma subjects. The control group had higher VD than the glaucoma group at the en face segmented layers of the optic disc (optic nerve head: 0.209±0.05 vs. 0.110±0.048, P<0.001; vitreoretinal interface: 0.086±0.045 vs. 0.052±0.034, P=0.001; radial peripapillary capillary: 0.146±0.040 vs. 0.053±0.036, P<0.001; and choroid: 0.228±0.074 vs. 0.165±0.062, P<0.001). Similarly, the VD at the macula was also greater in controls than glaucoma patients (superficial retina capillary plexus: 0.115±0.016 vs. 0.088±0.027, P<0.001; deep retina capillary plexus: 0.233±0.027 vs. 0.136±0.073, P<0.001; outer retinal capillary plexus: 0.190±0.057 vs. 0.136±0.105, P=0.036; and choriocapillaris: 0.225±0.053 vs. 0.153±0.068, P<0.001. The AUROC was highest for optic disc radial peripapillary capillary (0.96), followed by nerve head (0.92) and optic disc choroid (0.76). At the macula, the AUROC was highest for deep retina (0.86), followed by choroid (0.84), superficial retina (0.81), and outer retina (0.72). CONCLUSIONS: Microvascular density of the optic disc and macula in glaucoma patients was reduced compared with healthy controls. VD of both optic disc and macula had a high diagnostic ability in differentiating healthy and glaucoma eyes.

Optical coherence tomography angiography of the macula and optic nerve head: microvascular density and test-retest repeatability in normal subjects.

BACKGROUND: Despite the potential usefulness of optical coherence tomography angiography in retinal and optic disc conditions, the reliability of the imaging modality remains unclear. This study set out to measure the microvascular density of macula and optic disc by mean of optical coherence tomography angiography and report the repeatability of the vessel density measurements. METHODS: Cross sectional observational cohort study. Subjects with normal eyes were recruited. Two sets of optical coherence tomography angiography images of macula and optic nerve head were acquired during one visit. Novel in-house developed software was used to count the pixels in each images and to compute the microvessel density of the macula and optic disc. Data were analysed to determine the measurement repeatability. RESULTS: A total of 176 eyes from 88 consecutive normal subjects were recruited. For macular images, the mean vessel density at superficial retina, deep retina, outer retina and choriocapillaries segment was OD 0.113 and OS 0.111, OD 0.239 and OS 0.230, OD 0.179 and OS 0.164, OD 0.237 and OS 0.215 respectively. For optic disc images, mean vessel density at vitreoretinal interface, radial peripapillary capillary, superficial nerve head and disc segment at the level of choroid were OD 0.084 and OS 0.085, OD 0.140 and OS 0.138, OD 0.216 and OS 0.209, OD 0.227 and OS 0.236 respectively. The measurement repeatability tests showed that the coefficient of variation of macular scans, for right and left eyes, ranged from 6.4 to 31.1% and 5.3 to 59.4%. Likewise, the coefficient of variation of optic disc scans, for right and left eyes, ranged from 14.3 to 77.4% and 13.5 to 75.3%. CONCLUSIONS: Optical coherence tomography angiography is a useful modality to visualise the microvasculature plexus of macula and optic nerve head. The vessel density measurement of macular scan by mean of optical coherence tomography angiography demonstrated good repeatability. The optic disc scan, on the other hand, showed a higher coefficient of variation indicating a lower measurement repeatability than macular scan. Interpretation of optical coherence tomography angiography should take into account test-retest repeatability of the imaging system. TRIAL REGISTRATION: National Healthcare Group Domain Specific Review Board ( NHG DSRB ) Singapore. DSRB Reference: 2015/00301.

Glaucoma classification from retina optical coherence tomography angiogram.

This paper presents a new method for classification of retina into glaucoma and non-glaucoma cases based on optical coherence tomography angiogram (OCTA). The key idea here is to analyze the retinal microvasculature in the optic disc area of an enface OCTA for glaucoma classification. To facilitate this analysis, we propose a way to extract a so-called "optic disc microvasculature" region and then propose several features that will be extracted from this microvasculature region. A machine classifier is then trained using the designated features and subsequently used to classify the OCTA data. We show that our proposed approach works well on the tested dataset.

Agreement of angle closure assessments between gonioscopy, anterior segment optical coherence tomography and spectral domain optical coherence tomography.

AIM: To determine angle closure agreements between gonioscopy and anterior segment optical coherence tomography (AS-OCT), as well as gonioscopy and spectral domain OCT (SD-OCT). A secondary objective was to quantify inter-observer agreements of AS-OCT and SD-OCT assessments. METHODS: Seventeen consecutive subjects (33 eyes) were recruited from the study hospital's Glaucoma clinic. Gonioscopy was performed by a glaucomatologist masked to OCT results. OCT images were read independently by 2 other glaucomatologists masked to gonioscopy findings as well as each other's analyses of OCT images. RESULTS: Totally 84.8% and 45.5% of scleral spurs were visualized in AS-OCT and SD-OCT images respectively (P<0.01). The agreement for angle closure between AS-OCT and gonioscopy was fair at k=0.31 (95% confidence interval, CI: 0.03-0.59) and k=0.35 (95% CI: 0.07-0.63) for reader 1 and 2 respectively. The agreement for angle closure between SD-OCT and gonioscopy was fair at k=0.21 (95% CI: 0.07-0.49) and slight at k=0.17 (95% CI: 0.08-0.42) for reader 1 and 2 respectively. The inter-reader agreement for angle closure in AS-OCT images was moderate at 0.51 (95% CI: 0.13-0.88). The inter-reader agreement for angle closure in SD-OCT images was slight at 0.18 (95% CI: 0.08-0.45). CONCLUSION: Significant proportion of scleral spurs were not visualised with SD-OCT imaging resulting in weaker inter-reader agreements. Identifying other angle landmarks in SD-OCT images will allow more consistent angle closure assessments. Gonioscopy and OCT imaging do not always agree in angle closure assessments but have their own advantages, and should be used together and not exclusively.