Joong Won Shin

Quantitative optical coherence tomography angiography of macular vascular structure and foveal avascular zone in glaucoma

Objective The study aimed to evaluate the quantitative characteristics of the macular vessel density (VD) and foveal avascular zone (FAZ) in glaucoma using optical coherence tomography angiography (OCT-A). Design Cross-sectional, age- and sex-matched case–control study. Methods Fifty-two eyes of 52 patients with primary open angle glaucoma and 52 eyes from 52 healthy participants were recruited retrospectively. OCT-A was performed on a 3 x 3-mm macular region centered on the fovea. OCT-A scans were manually graded to define the FAZ. Parafoveal VD in superficial and deep retina were analyzed in the circular- and quadrant-segmented zone. The FAZ parameters included size, perimeter, and circularity index. The regression analysis among VD and FAZ-related parameters and ocular parameters was performed, and the diagnostic ability was calculated with refractive error adjusted. Results For both groups, the mean age and the sex ratio was not different between groups. With refractive error adjusted, the average macular VD was lower in glaucoma than in the control group for superficial (P = 0.013), deep (P<0.001), and the whole retina (P = 0.002). There were increased FAZ perimeter and decreased FAZ circularity index in glaucoma when compared with controls (P<0.001). In the multivariate regression models, FAZ circularity index were significantly associated with decreased peripapillary RNFL thickness (P = 0.007) and macular GCIPL thickness (P = 0.009) measured by OCT. The refractive-error adjusted area under receiver operating characteristics was highest for FAZ circularity index (0.905; 95% CI, 0.844–0.966), followed by temporal deep retinal VD (0.870; 95% CI, 0.803–0.937) and FAZ perimeter (0.858; 95% CI, 0.784–0.932). Conclusions Decreased macular VD, increased FAZ perimeter, and decreased FAZ circularity index were observed in eyes with glaucoma using OCT-A. With refractive error adjusted, these parameters showed considerable diagnostic value for glaucoma. FAZ circularity index may be a novel biomarker representing disruption of the parafoveal capillary network in glaucoma, as supported by its association with structural parameters.

Regional vascular density–visual field sensitivity relationship in glaucoma according to disease severity

Aims To study whether there are global and regional relationships between peripapillary vascular density (pVD) assessed by optical coherence tomography angiography (OCT-A) and visual field (VF) mean sensitivity at different glaucoma stages. Methods Microvascular images and peripapillary retinal nerve fibre layer (pRNFL) thicknesses were obtained using a Cirrus OCT-A device in 91 glaucoma subjects. The pVD was measured at various spatial locations according to the Garway-Heath map, using a MATLAB software (The MathWorks, Natick, Massachusetts). VF mean sensitivity (VFMS) was recorded in the 1/L scale. Global and regional vasculature–function (pVD vs VFMS) relationships were assessed in separate patient groups at mild and moderate-to-advanced stages of glaucoma. Results The pVDs at superotemporal and inferotemporal regions were significantly associated with corresponding VFMS in mild glaucoma (p<0.05). In moderate-to-advanced glaucoma, there were significant associations between pVD and VFMS, regardless of location. The association between global pVD and VFMS was significantly stronger than that between global pRNFL thickness and VFMS in moderate-to-advanced stage glaucoma (p <0.05). Conclusion Global and regional pVD measured by OCT-A was significantly associated with corresponding VFMS in moderate-to-advanced glaucoma. OCT-A may be useful in monitoring glaucoma at various stages.

Factors Associated With Visual Field Progression in Cirrus Optical Coherence Tomography-guided Progression Analysis: A Topographic Approach

Purpose: To identify factors associated with visual field (VF) progression in optical coherence tomography (OCT)-guided progression analysis (GPA) using a topographic approach. Methods: Topographic components of OCT-GPA maps (Cirrus HD-OCT; Carl Zeiss Meditec) were classified according to location (temporal, superotemporal, superonasal, nasal, inferornasal, and inferotemporal), size (small, medium, and large), shape (wedge and irregular types), and pattern of retinal nerve fiber layer (RNFL) progression (widening, deepening, and new development). All positive findings in OCT-GPA (RNFL thickness maps, profiles, and average RNFL thickness) were defined as strong RNFL progression. VF progression was determined by linear regression analysis of VF mean deviation over time. Univariate and multivariate logistic regression analyses were performed to evaluate the association of VF progression with OCT-GPA parameters. Results: In total, 276 primary open-angle glaucoma patients were followed up for 5.1 years. According to OCT-GPA, 89 eyes were found to have RNFL progression. Of these, VF progression was detected in 27 (30.3%) eyes. Eyes with progressed VF group showed topographically different characteristics, which were wedge-shaped (80.6%), large-sized (40.0%), and widening (69.5%) or deepening (11.1%) pattern of RNFL progression in the inferotemporal (44.4%) and superotemporal (30.6%) regions, compared with eyes with non-progressed VF group. In multivariate analysis, strong RNFL progression and widening or deepening pattern of RNFL progression were significantly associated with VF progression (P=0.012 and 0.016, respectively). Conclusions: Topographic analysis in OCT-GPA maps showed different characteristics between progressed VF and nonprogressed VF groups. Glaucoma patients with widening or deepening pattern of RNFL progression should be carefully monitored for greater risk of VF progression.

Peripapillary Microvascular Improvement and Lamina Cribrosa Depth Reduction After Trabeculectomy in Primary Open-Angle Glaucoma

Purpose To evaluate peripapillary microvascular changes in patients with primary open-angle glaucoma (POAG) after trabeculectomy using optical coherence tomography (OCT) angiography, and to determine the influence of lamina cribrosa (LC) displacement on changes in peripapillary microvasculature. Methods The peripapillary retinal microvasculature and LC were imaged using OCT angiography and OCT-enhanced depth imaging, respectively. The microvasculature and LC depth (LCD) were measured before, and 1 week, 1 month, and 3 months after trabeculectomy. The microvascular improvement was arbitrarily defined as a reduction >30% of the area of vascular dropout (blue/black areas with <20% vessel density on the color-coded vessel density map). LCD was determined as the mean of vertical distance between the anterior LC surface and a reference plane of Bruchs membrane. Results Thirty-one eyes of 31 POAG patients were included. At 3 months postoperatively, intraocular pressure (IOP) and LCD were significantly decreased from 26.3 ± 11.8 mm Hg to 12.5 ± 3.6 mm Hg, and 501.1 ± 130.2 μm to 455.8 ± 112.7 μm, respectively (all P < 0.001), compared with baseline. The microvascular improvement was observed in 19 eyes (61.3%) at 3 months after trabeculectomy. The maximal reductions in IOP and LCD were significantly greater in eyes with improved microvasculature compared to eyes without improvement (P = 0.020 and P = 0.005). The microvascular improvement was significantly associated with maximal reduction in LCD (odds ratio, 1.062; P = 0.026). Conclusions Trabeculectomy can improve peripapillary retinal microcirculation in patients with POAG. This finding suggests that the reduction of LCD induced by lowering IOP may affect peripapillary microvascular improvement in eyes with POAG.

Glaucoma Diagnostic Capabilities of Foveal Avascular Zone Parameters Using Optical Coherence Tomography Angiography According to Visual Field Defect Location

Purpose: To assess the diagnostic ability of foveal avascular zone (FAZ) parameters to discriminate glaucomatous eyes with visual field defects (VFDs) in different locations (central vs. peripheral) from normal eyes. Patients and Methods: Totally, 125 participants were separated into 3 groups: normal (n=45), glaucoma with peripheral VFD (PVFD, n=45), and glaucoma with central VFD (CVFD, n=35). The FAZ area, perimeter, and circularity and parafoveal vessel density were calculated from optical coherence tomography angiography images. The diagnostic ability of the FAZ parameters and other structural parameters was determined according to glaucomatous VFD location. Associations between the FAZ parameters and central visual function were evaluated. Results: A larger FAZ area and longer FAZ perimeter were observed in the CVFD group than in the PVFD and normal groups. The FAZ area, perimeter, and circularity were better in differentiating glaucomatous eyes with CVFDs from normal eyes [areas under the receiver operating characteristic curves (AUC), 0.78 to 0.88] than in differentiating PVFDs from normal eyes (AUC, 0.51 to 0.64). The FAZ perimeter had a similar AUC value to the circumpapillary retinal nerve fiber layer and macular ganglion cell-inner plexiform layer thickness for differentiating eyes with CVFDs from normal eyes (all P>0.05, the DeLong test). The FAZ area was significantly correlated with central visual function (&bgr;=−112.7, P=0.035, multivariate linear regression). Conclusions: The FAZ perimeter had good diagnostic capability in differentiating glaucomatous eyes with CVFDs from normal eyes, and may be a potential diagnostic biomarker for detecting glaucomatous patients with CVFDs.

The Effect of Optic Disc Center Displacement on Retinal Nerve Fiber Layer Measurement Determined by Spectral Domain Optical Coherence Tomography

Purpose To investigate the effect of optic disc center displacement on retinal nerve fiber layer (RNFL) measurement determined by spectral domain optical coherence tomography (SD-OCT). Methods The optic disc center was manipulated at 1-pixel intervals in horizontal, vertical, and diagonal directions. According to the manipulated optic disc center location, the RNFL thickness data were resampled: (1) at a 3.46-mm diameter circle; and (2) between a 2.5-mm diameter circle and 5.4-mm square. Error was calculated between the original and resampled RNFL measurements. The tolerable error threshold of the optic disc center displacement was determined by considering test-retest variability of SD-OCT. The unreliable zone was defined as an area with 10% or more variability. Results The maximum tolerable error thresholds of optic disc center displacement on the RNFL thickness map were distributed from 0.042 to 0.09 mm in 8 directions. The threshold shape was vertically elongated. Clinically important unreliable zones were located: (1) at superior and inferior region in the vertical displacement; (2) at inferotemporal region in the horizontal displacement, and (3) at superotemporal or inferotemporal region in the diagonal displacement. The unreliable zone pattern and threshold limit varied according to the direction of optic disc displacement. Conclusions Optic disc center displacement had a considerable impact on whole RNFL thickness measurements. Understanding the effect of optic disc center displacement could contribute to reliable RNFL measurements.

Patterns of Progressive Ganglion Cell–Inner Plexiform Layer Thinning in Glaucoma Detected by OCT

PURPOSE To investigate the spatial characteristics and patterns of progressive macular ganglion cell-inner plexiform layer (GCIPL) thinning in glaucomatous eyes assessed by OCT Guided Progression Analysis (GPA). DESIGN Longitudinal, retrospective, observational study. PARTICIPANTS Two hundred ninety-two eyes of 192 patients with primary open-angle glaucoma with a mean follow-up of 6.0 years (range, 3.2-8.1 years) were included. METHODS Macular GCIPL imaging and visual field (VF) examination were performed at 6-month intervals for 3 years or more. Progressive GCIPL thinning was evaluated by a Cirrus HD-OCT (Carl Zeiss Meditec, Dublin, CA) GPA device. Spatial characteristics of progressive GCIPL thinning were assessed by the GCIPL thickness change map. The pattern of progressive GCIPL thinning was evaluated by comparing the baseline GCIPL thickness deviation map and the final GCIPL thickness change map. Visual field progression was determined by Early Manifest Glaucoma Trial criteria and linear regression of the VF index. MAIN OUTCOME MEASURES Spatial characteristics and patterns of progressive GCIPL thinning. RESULTS Seventy-two eyes of 62 participants (24.7% [72/292]) showed progressive GCIPL thinning in the GCIPL thickness change map. Progressive GCIPL thinning was detected most frequently (25.0%) at 2.08 mm from the fovea, and it extended in an arcuate shape in the inferotemporal region (250°-339°). Compared with the baseline GCIPL defects, the progressive GCIPL thinning extended toward the fovea and optic disc. The most common pattern of progressive GCIPL thinning was widening of GCIPL defects (42 eyes [58.3%]), followed by deepening of GCIPL defects (19 eyes [26.4%]) and newly developed GCIPL defects (15 eyes [20.8%]). Visual field progression was accompanied by progressive GCIPL thinning in 41 of 72 eyes (56.9%). Progressive GCIPL thinning preceded (61.0% [25/41]) or occurred concomitantly with (21.9% [9/41]) VF progression. CONCLUSIONS The use of OCT GPA maps offers an effective approach to evaluate the topographic patterns of progressive GCIPL thinning in glaucomatous eyes. Progression of GCIPL thinning occurred before apparent progression on standard automated perimetry in most glaucomatous eyes. Understanding specific patterns and sequences of macular damage may provide important insights in the monitoring of glaucomatous progression.

Progressive change in peripapillary atrophy in myopic glaucomatous eyes

Aim To evaluate the progressive change in peripapillary atrophy (PPA) according to its shape and to explore the relationship between PPA progression and glaucoma worsening in myopic eyes. Methods A total of 159 eyes of 159 patients with myopic (axial length (AXL) >24 mm) glaucoma (mean follow-up 4.4 years, 35 eyes with minimal PPA, 40 concentric-type PPA eyes (>270° around the optic disc) and 84 eccentric-type PPA eyes (<270°)) were included. Sequential stereoscopic colour optic disc photographs were evaluated to qualitatively determine PPA progression. Factors associated with PPA progression were explored by Cox proportional hazard modelling in each PPA group. Results Patients with concentric PPA were older than patients with eccentric PPA (54.1±11.7 vs 44.1±11.7 years; P<0.001), and AXL was longer in the eccentric group than in the other groups (25.54±1.68 vs 25.28±1.53 vs 26.41±1.29 mm; P<0.001). Twenty-six eyes (65%) in the concentric group and 36 eyes (42.9%) in the eccentric group showed PPA progression. Older age (hazard ratio (HR) 1.059, P=0.008), worse baseline visual field mean deviation (HR 0.857, P=0.009) and greater baseline PPA area (HR 1.000, P=0.012) were associated with PPA progression in the concentric type. Glaucoma progression (HR 3.690, P=0.002) and longer AXL (HR 1.521, P=0.002) were associated with PPA progression in the eccentric type. Conclusions Relationship between glaucoma worsening and PPA progression was strongest in myopic glaucomatous eyes with eccentric type PPA.

Sub-classification of myopic glaucomatous eyes according to optic disc and peripapillary features

Purpose To investigate the sub-classification of myopic glaucomatous eyes by optic disc and peripapillary features. Methods Optic disc tilt and torsion were determined from retinal nerve fiber layer photographs. Based on the location of the Bruch’s membrane (BM) opening within the β-zone of the peripapillary atrophy (PPA) area, the widths of β-zone PPA (PPA1W), PPA+BM (PPA2W), and PPA-BM (PPA3W) were measured with enhanced depth imaging spectral-domain optical coherence tomography. Cluster analysis that employed partitioning around medoids was performed with these parameters, the presence of inward rotation of BM ending axial length (AXL), and central corneal thickness. Results A total of 115 eyes (AXL≥24 mm) were included. Two clusters produced maximum overall silhouette widths (average = 0.43). Visual field (VF) mean deviation was not different between cluster 1 (52 eyes; -4.02±3.01 dB) and cluster 2 (63 eyes; -5.21±5.62 dB; p = 0.174). In cluster 1 compared to cluster 2, optic disc tilt was significantly greater, PPA1W and PPA3W were longer, and AXL was longer (all p<0.001). The presence of an inward rotation of BM ending was more frequent in cluster 2 (p = 0.043). Forty-one eyes (78.8%) in cluster 1 had superior VF defects while 10 eyes (19.2%) had inferior defects, and only one eye (2%) had defects in both hemifields. Eyes in cluster 2 were more evenly distributed: 55.6% had superior defects, 34.9% had inferior defects, and 9.5% had defects in both hemifields (p = 0.023). Conclusions Myopic glaucomatous eyes characterized by optic disc and peripapillary configurations can be classified as two distinct types, and the most distinct difference between the two was degree of optic disc tilt and width of PPA. The location of VF defects were also significantly different between two clusters.

Topographic Relationship between Optic Disc Torsion and ß-Zone Peripapillary Atrophy in the Myopic Eyes of Young Patients with Glaucomatous-Appearing Visual Field Defects

Purpose: The purpose of this study was to assess the topographic correlation between optic disc torsion (ODT) and beta-zone peripapillary atrophy (&bgr;-PPA) in young patients with myopia and glaucomatous-appearing visual field defects (VFDs). Patients and Methods: We consecutively recruited 110 eyes of 110 young patients with myopia and glaucomatous-appearing VFDs. Retinal nerve fiber layer (RNFL) and macular ganglion cell inner plexiform layer (mGCIPL) thicknesses were measured to compare between the groups with different ODT directions. For evaluating topographic correlation, the direction and degree of ODT and the direction and angles of &bgr;-PPA and point of maximum radial extent (PMRE) of &bgr;-PPA were measured on fundus photographs. Multivariate logistic regression analysis was performed to determine the clinical factors associated with inferior ODT direction. The relationships between torsional degree and clinical variables were evaluated using linear regression analyses. Results: Among the 110 eyes, 19 had superior ODT and 91 had inferior ODT. Compared with myopic eyes with superior ODT, those with inferior ODT showed less severity of glaucoma as determined by RNFL or mGCIPL thickness and had a longer axial length, greater amount of optic disc tilt, larger &bgr;-PPA angle, and higher ratio of &bgr;-PPA area and disc area. ODT direction was significantly associated with the locations of &bgr;-PPA and PMRE. Torsional degree was significantly correlated with the &bgr;-PPA angle. Conclusions: ODT direction showed a significant association with the locations of &bgr;-PPA and PMRE of &bgr;-PPA. Torsional degree was correlated with the &bgr;-PPA angle in the myopic eyes of young patients with glaucomatous-appearing VFDs.