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PURPOSE: This study uses deep neural network-generated rim-to-disc area ratio (RADAR) measurements and the disc damage likelihood scale (DDLS) to measure the rate of optic disc rim loss in a large cohort of glaucoma patients. METHODS: A deep neural network was used to calculate RADAR and DDLS for each optic disc photograph (ODP). Patient demographics, diagnosis, intraocular pressure (IOP), and mean deviation (MD) from perimetry were analyzed as risk factors for faster progression of RADAR. Receiver operating characteristic (ROC) curves were used to compare RADAR and DDLS in their utility to distinguish glaucoma from glaucoma suspect (GS) and for detecting glaucoma progression. RESULTS: A total of 13,679 ODPs with evidence of glaucomatous optic nerve damage from 4106 eyes of 2407 patients with glaucoma or GS were included. Of these eyes, 3264 (79.5%) had a diagnosis of glaucoma, and 842 (20.5%) eyes were GS. Mean ± SD baseline RADAR of GS and glaucoma were 0.67 ± 0.13 and 0.57 ± 0.18, respectively (P < 0.001). Older age, greater IOP fluctuation, baseline MD, right eye, and diagnosis of secondary open-angle glaucoma were associated with slope of RADAR. The mean baseline DDLS of GS and glaucoma were 3.78 and 4.39, respectively. Both RADAR and DDLS showed a less steep slope in advanced glaucoma. In glaucoma, the change of RADAR and DDLS correlated with the corresponding change in MD. RADAR and DDLS had a similar ability to discriminate glaucoma from GS and detect disease progression. Area under the ROC curve of RADAR and DDLS was 0.658 and 0.648. CONCLUSIONS: Automated calculation of RADAR and DDLS with a neural network can be used to evaluate the extent and long-term rate of optic disc rim loss and is further evidence of long-term nerve fiber loss in treated patients with glaucoma. TRANSLATIONAL RELEVANCE: Our study provides a large clinic-based experience for RADAR and DDLS measurements in GS and glaucoma with a neural network.

AIM: We tested the hypothesis that visual field (VF) progression can be predicted with a deep learning model based on longitudinal pairs of optic disc photographs (ODP) acquired at earlier time points during follow-up. METHODS: 3919 eyes (2259 patients) with ≥2 ODPs at least 2 years apart, and ≥5 24-2 VF exams spanning ≥3 years of follow-up were included. Serial VF mean deviation (MD) rates of change were estimated starting at the fifth visit and subsequently by adding visits until final visit. VF progression was defined as a statistically significant negative slope at two consecutive visits and final visit. We built a twin-neural network with ResNet50-backbone. A pair of ODPs acquired up to a year before the VF progression date or the last VF in non-progressing eyes were included as input. Primary outcome measures were area under the receiver operating characteristic curve (AUC) and model accuracy. RESULTS: The average (SD) follow-up time and baseline VF MD were 8.1 (4.8) years and -3.3 (4.9) dB, respectively. VF progression was identified in 761 eyes (19%). The median (IQR) time to progression in progressing eyes was 7.3 (4.5-11.1) years. The AUC and accuracy for predicting VF progression were 0.862 (0.812-0.913) and 80.0% (73.9%-84.6%). When only fast-progressing eyes were considered (MD rate < -1.0 dB/year), AUC increased to 0.926 (0.857-0.994). CONCLUSIONS: A deep learning model can predict subsequent glaucoma progression from longitudinal ODPs with clinically relevant accuracy. This model may be implemented, after validation, for predicting glaucoma progression in the clinical setting.

PURPOSE: Demonstrate that a novel Bayesian hierarchical spatial longitudinal (HSL) model improves estimation of local macular ganglion cell complex (GCC) rates of change compared to simple linear regression (SLR) and a conditional autoregressive (CAR) model. METHODS: We analyzed GCC thickness measurements within 49 macular superpixels in 111 eyes (111 patients) with four or more macular optical coherence tomography scans and two or more years of follow-up. We compared superpixel-patient-specific estimates and their posterior variances derived from the latest version of a recently developed Bayesian HSL model, CAR, and SLR. We performed a simulation study to compare the accuracy of intercept and slope estimates in individual superpixels. RESULTS: HSL identified a significantly higher proportion of significant negative slopes in 13/49 superpixels and a significantly lower proportion of significant positive slopes in 21/49 superpixels than SLR. In the simulation study, the median (tenth, ninetieth percentile) ratio of mean squared error of SLR [CAR] over HSL for intercepts and slopes were 1.91 (1.23, 2.75) [1.51 (1.05, 2.20)] and 3.25 (1.40, 10.14) [2.36 (1.17, 5.56)], respectively. CONCLUSIONS: A novel Bayesian HSL model improves estimation accuracy of patient-specific local GCC rates of change. The proposed model is more than twice as efficient as SLR for estimating superpixel-patient slopes and identifies a higher proportion of deteriorating superpixels than SLR while minimizing false-positive detection rates. TRANSLATIONAL RELEVANCE: The proposed HSL model can be used to model macular structural measurements to detect individual glaucoma progression earlier and more efficiently in clinical and research settings.

BACKGROUND: Which phenotypes are we able to recognize in the optic nerve of patients with primary open angle glaucoma? METHODS: Retrospective interventional case series. 885 eyes from 885 patients at an outpatient tertiary care centre who met specified criteria for POAG were included. Disc photographs were classified by three glaucoma specialists into the following phenotypes according to their predominant characteristics: (1) concentric rim thinning, (2) focal rim thinning, (3) acquired pit of the optic nerve (APON), (4) tilted, (5) extensive peripapillary atrophy (PPA), and (6) broad rim thinning. Demographic, medical, and ocular data were collected. Kruskal-Wallis was used as a non-parametric test and pairwise comparison was performed by using Wilcoxon rank sum test corrected. RESULTS: Phenotypic distribution was as follows: 398(45%) focal thinning, 153(18%) concentric thinning, 153(17%) broad thinning, 109(12%) tilted, 47(5%) extensive PPA and 25(3%) APON. Phenotypic traits of interest included a higher proportion of female patients with the focal thinning phenotype (p = 0.015); myopia (p = 0.000), Asian race (OR: 8.8, p = 0.000), and younger age (p = 0.000) were associated with the tilted phenotype; the concentric thinning patients had thicker RNFL (p = 0.000), higher MD (p = 0.008) and lower PSD (p = 0.043) than broad thinning, despite no difference in disc sizes (p = 0.849). The focal thinning group had a localized VF pattern with high PSD compared to concentric thinning (p = 0.005). CONCLUSION: We report six phenotypic classifications of POAG patients with demographic and ocular differences between phenotypes. Future refinement of phenotypes should allow enhanced identification of genetic associations and improved individualization of patient care.

PURPOSE: Predict central 10° global and local visual field (VF) measurements from macular optical coherence tomography (OCT) volume scans with deep learning (DL). METHODS: This study included 1121 OCT volume scans and 10-2 VFs from 289 eyes (257 patients). Macular scans were used to estimate 10-2 VF mean deviation (MD), threshold sensitivities (TS), and total deviation (TD) values at 68 locations. A three-dimensional (3D) convolutional neural network based on the 3D DenseNet121 architecture was used for prediction. We compared DL predictions to those from baseline linear models. We carried out 10-fold stratified cross-validation to optimize generalizability. The performance of the DL and baseline models was compared based on correlations between ground truth and predicted VF measures and mean absolute error (MAE; ground truth - predicted values). RESULTS: Average (SD) MD was -9.3 (7.7) dB. Average (SD) correlations between predicted and ground truth MD and MD MAE were 0.74 (0.09) and 3.5 (0.4) dB, respectively. Estimation accuracy deteriorated with worsening MD. Average (SD) Pearson correlations between predicted and ground truth TS and MAEs for DL and baseline model were 0.71 (0.05) and 0.52 (0.05) (P < 0.001) and 6.5 (0.6) and 7.5 (0.5) dB (P < 0.001), respectively. For TD, correlation (SD) and MAE (SD) for DL and baseline models were 0.69 (0.02) and 0.48 (0.05) (P < 0.001) and 6.1 (0.5) and 7.8 (0.5) dB (P < 0.001), respectively. CONCLUSIONS: Macular OCT volume scans can be used to predict global central VF parameters with clinically relevant accuracy. TRANSLATIONAL RELEVANCE: Macular OCT imaging may be used to confirm and supplement central VF findings using deep learning.

PURPOSE: To compare rates of change (RoC) of peripapillary retinal nerve fiber layer (RNFL) and Bruch membrane opening-based minimum rim width (BMO-MRW) thickness in moderate-to-advanced glaucoma. DESIGN: Prospective cohort study. METHODS: Longitudinal optical coherence tomography (OCT) optic nerve head volume scans of 113 eyes of 113 glaucoma patients with moderate-to-advanced or central damage were exported. This study estimated and compared global and sectoral RoC with linear mixed effects models and simple linear regression (SLR) of RNFL and BMO-MRW thickness. Permutation analyses were used to test significance of RoC in the SLR model. It also compared longitudinal signal-to-noise ratios (LSNR) defined as RoC divided by residual standard deviation (SD) between the two groups. RESULTS: Mean (SD) follow-up and median (IQR) OCT scan sessions were 5.2 (1.3) years and 10 (8-11), respectively. Baseline average (SD) visual field mean deviation was -9.2 (5.8) dB. Based on SLR, a higher proportion of significant negative RNFL RoC was observed compared to BMO-MRW in the inferotemporal (35% vs 20%; P = .015) and inferonasal (42% vs 17%; P < .001) sectors. Permutation analyses also demonstrated a higher proportion of worsening RNFL RoC than BMO-MRW in the inferotemporal (P = .026) and inferonasal (P < .001) sectors along with overall lower positive RoC. Longitudinal signal-to-noise ratios for RNFL were significantly more negative than for BMO-MRW globally, and in the inferotemporal, inferonasal, and superonasal sectors (P ≤ .01). CONCLUSIONS: Longitudinal RNFL OCT measurements are more likely to detect structural change and demonstrate better LSNR compared with BMO-MRW in eyes with central or moderate-to-advanced glaucoma damage at baseline.

PrcisWe report the survival of surgical revision to glaucoma drainage devices for several indications in a large cohort of patients, with an overall success rate of 45% at 36 months.PurposeTo evaluate the outcomes of surgical revision for complications of glaucoma drainage devices.MethodsThree hundred thirty-five eyes of 318 patients who underwent tube revision or removal at University of California Los Angeles (UCLA) Jules Stein Eye Institute between 1997 and 2019 were included. The pre-defined primary outcome measure was surgical success of the initial revision, defined as resolution of the condition with no additional revisions required, no functionally significant change in vision, and no instances of intraocular pressure > 21 mmHg at 2 consecutive visits postoperatively. Kaplan-Meier survival analysis was applied to evaluate survival at 36 months based on these criteria. The Wilcoxon paired test was used to compare mean preoperative and postoperative intraocular pressure, medication usage, and visual acuity.ResultsOverall, survival of revised tubes at 36 months was 45%. The 4 most common indications for revision were exposure of the implant (42% of all revisions), occlusion (14%), corneal failure or threat of failure (12%), and hypotony (11%). Survival at 36 months for each of these indications was 44%, 45%, 52%, and 37%, respectively.ConclusionsThese results suggest that eyes with glaucomatous damage with long-term glaucoma drainage device complications can still have a reasonably successful outcome when a revision is performed. However, with substantial rates of vision loss and a frequent need for additional revisions to manage complications, managing patient expectations for success and making them aware of the likelihood of additional surgeries or failure is important.

BACKGROUND/OBJECTIVE: Management of concomitant cataract and glaucoma depends on the stage of glaucoma and the patients situation. There are different surgical options for handling visually significant cataract and mild-to-moderate open-angle glaucoma (OAG). We aimed to compare the one-year results of phacoemulsification alone versus phacoviscocanalostomy in these patients. SUBJECTS/METHODS: This was a parallel-arm, single-masked, randomized-controlled trial, conducted at Farabi Eye Hospital, Tehran, Iran between January 2016 and January 2018. We enrolled 89 eyes from 89 patients with mild-to-moderate primary OAG or pseudoexfoliative glaucoma (PEXG) with visually significant age-related cataract. They randomly underwent phacoemulsification alone (n = 44) or combined phaco-viscocanalostomy (n = 45). All patients had a 12-month follow-up period, and the mean intraocular pressure (IOP), the number of antiglaucoma medications, and complete and qualified success rates were compared. RESULTS: After the 1st and 3rd months, the mean IOP showed significantly decreased in the phaco-visco group compared to the phaco group (P

PurposeWe compared ganglion cell layer (GCL) and inner plexiform layer (IPL) rates of change (RoC) in patients with glaucoma suspect (GS) and established glaucoma (EG) to test the hypothesis that IPL thickness changes would occur earlier than GCL changes in eyes with early damage.DesignProspective, cohort study.MethodsA total of 64 GS eyes (46 patients) and 112 EG eyes (112 patients) with ≥2 years of follow-up and ≥3 macular optical coherence tomography scans were included. GCL and IPL superpixel thickness measurements were exported. A Bayesian hierarchical model with random intercepts/slopes and random residual variances was fitted to estimate RoC in individual superpixels. Normalized RoC and proportions of superpixels with significantly negative and positive GCL and IPL RoC were compared within the groups.ResultsThe average (SD) follow-up time and number of scans were 3.5 (0.7) years and 4.2 (1.0), respectively, in the GS group and 3.6 (0.4) years and 7.3 (1.1) in the EG group. Mean (SD) normalized RoC was faster for GCL than IPL (-0.69 [0.05] vs -0.33 [0.04]) in the GS group, whereas it was faster for IPL (-0.47 [0.03] vs -0.28 [0.02]) in EG eyes. GCL RoC were significantly negative in 24 of 36 superpixels compared with 8 of 36 for IPL (P < .001) in GS eyes. In the EG group, 23 of 36 superpixels had significant negative IPL RoC compared with 13 of 36 superpixels for GCL (P = .006).ConclusionsGCL thickness is more likely to demonstrate change over time compared with IPL in glaucoma suspects. There is no evidence of preferential IPL thinning in eyes with suspected early glaucoma damage.

BACKGROUND/AIMS: To identify clinical characteristics and factors associated with microcystic macular edema (MME) in patients with primary open-angle glaucoma (POAG). METHODS: We included 315 POAG eyes between 2010 and 2019 with good-quality macular volume scans that had reliable visual fields (VF) available within 6 months in this observational retrospective cohort study. Eyes with retinal pathologies except for epiretinal membrane (ERM) were excluded. The inner nuclear layer was qualitatively assessed for the presence of MME. Global mean deviation (MD) and Visual Field Index (VFI) decay rates, superior and inferior MD rates and pointwise total deviation rates of change were estimated with linear regression. Logistic regression was performed to identify baseline factors associated with the presence of MME and to determine whether MME is associated with progressive VF loss. RESULTS: 25 out of 315 eyes (7.9%) demonstrated MME. The average (±SD) age and MD in eyes with and without MME was 57.2 (±8.7) versus 62.0 (±9.9) years (p=0.02) and -9.8 (±5.7) versus -4.9 (±5.3) dB (p0.49). CONCLUSIONS: More severe glaucoma and younger age were associated with MME. MME was not associated with faster global VF decay in this cohort. MME may confound monitoring of glaucoma with full macular thickness.

PurposeTo develop a structural metascore (SMS) that combines measurements from different devices and expresses them on a single scale to facilitate their long-term analysis.MethodsThree structural measurements (Heidelberg Retina Tomograph II [HRT] rim area, HD-Cirrus optical coherence tomography [OCT] average retinal nerve fiber layer [RNFL] thickness, Spectralis OCT RNFL global thickness) were normalized on a scale of 0 to 100 and converted to a reference value. The resultant metascores were plotted against time. SMS performance was evaluated to predict future values (internal validation), and correlations between the average grades assigned by three clinicians were compared with the SMS slopes (external validation).ResultsThe linear regression fit with the variance approach, and adjustment to a Spectralis equivalent was the best-performing approach; this was denominated metascore. Plots were created for 3416 eyes of 1824 patients. The average baseline age (± standard deviation) was 69.8 (±13.9), mean follow-up was 11.6 (±4.7) years, and mean number of structural scans per eye was 10.0 (±4.7). The mean numbers of scans per device were 3.8 (±2.5), 5.0 (±2.9), and 1.3 (±3.0) for HRT, Cirrus, and Spectralis, respectively. The metascore slopes' median was -0.3 (interquartile range 1.1). Correlations between the average grades assigned by the three clinicians and the metascore slopes were -0.51, -0.49, and -0.69 for the first (structural measurement printouts alone), second (metascore plots alone), and third (printouts + metascore plots) series of gradings, respectively. The average absolute predictive ability was 7.63/100 (whereas 100 = entire normalized scale).ConclusionsWe report a method that converts Cirrus global RNFL and HRT global rim area normalized measurements to Spectralis global RNFL equivalent values to facilitate long-term structural follow-up.Translational relevanceBecause glaucoma changes usually occur slowly, patients are often examined with different instruments during their follow-up, a method that "unifies" structural measurements provided by different devices, which could assist patients' longitudinal structural follow-up.

PurposeTo test the hypothesis that newly developed shape measures using optical coherence tomography (OCT) macular volume scans can discriminate patients with perimetric glaucoma from healthy subjects.MethodsOCT structural measures defining macular topography and volume were recently developed based on cubic Bézier curves. We exported macular volume scans from 135 eyes with glaucoma (133 patients) and 155 healthy eyes (85 subjects) and estimated global and quadrant-based measures. The best subset of measures to predict glaucoma was explored with a gradient boost model (GBM) with subsequent logistic regression. Accuracy and area under receiver operating curves (AUC) were the primary metrics. In addition, we separately investigated model performance in 66 eyes with mild glaucoma (mean deviation ≥ -6 dB).ResultsAverage (±SD) 24-2 mean deviation was -8.2 (±6.1) dB in eyes with glaucoma. The main predictive measures for glaucoma were temporal inferior rim height, nasal inferior pit volume, and temporal inferior pit depth. Lower values for these measures predicted higher risk of glaucoma. Sensitivity, specificity, and AUC for discriminating between healthy and glaucoma eyes were 81.5% (95% CI = 76.6-91.9%), 89.7% (95% CI = 78.7-94.2%), and 0.915 (95% CI = 0.882-0.948), respectively. Corresponding metrics for mild glaucoma were 84.8% (95% CI = 72.1%-95.5%), 85.8% (95% CI = 87.1%-97.4%), and 0.913 (95% CI = 0.867-0.958), respectively.ConclusionsNovel macular shape biomarkers detect early glaucoma with clinically relevant performance. Such biomarkers do not depend on intraretinal segmentation accuracy and may be helpful in eyes with suboptimal macular segmentation.Translational relevanceMacular shape biomarkers provide valuable information for detection of early glaucoma and may provide additional information beyond thickness measurements.

PurposeTo test the hypothesis that macular ganglion cell complex (GCC) thickness from optical coherence tomography (OCT) provides a stronger change signal regardless of glaucoma severity compared with other macular measures.DesignProspective cohort study.MethodsEyes were from 112 patients with moderate to severe glaucoma at baseline from a tertiary glaucoma center. In each 3° × 3° macular superpixel, a hierarchical Bayesian random intercept and slope model with random residual variance was fit to longitudinal full macular thickness (FMT), outer retina layers, GCC, ganglion cell-inner plexiform layer (GCIPL), and ganglion cell layer (GCL) measurements. We estimated population- and individual-level slopes and intercepts. Proportions of substantial worsening and improving superpixel slopes were compared between layers and in superpixels with mild to moderate vs severe damage (total deviation of corresponding visual field location ≥ -8 vs < -8 dB).ResultsMean (SD) follow-up time and baseline 10-2 visual field mean deviation were 3.6 (0.4) years and -8.9 (5.9) dB, respectively. FMT displayed the highest proportion of significant negative slopes (1932/3519 [54.9%]), followed by GCC (1286/3519 [36.5%]), outer retina layers (1254/3519 [35.6%]), (GCIPL) (1075/3518 [30.6%]), and (GCL) (698/3518 [19.8%]). Inner macular measures detected less worsening in the severe glaucoma group; yet GCC (223/985 [22.6%]) identified the highest proportion (GCIPL: 183/985 [18.6%]; GCL: 106/985 [10.8%]). Proportions of positive rates were small and comparable among all measures.ConclusionsGCC is the optimal macular measure for detection of structural change in eyes with moderate to severe glaucoma. Although a higher proportion of worsening superpixels was observed for FMT, a large portion of FMT change could be attributed to changes in outer retina layers.

Because of their diverse functionalities in cells, lipids are of primary importance when characterizing molecular profiles of physiological and disease states. Imaging mass spectrometry (IMS) provides the spatial distributions of lipid populations in tissues. Referenced Kendrick mass defect (RKMD) analysis is an effective mass spectrometry (MS) data analysis tool for classification and annotation of lipids. Herein, we extend the capabilities of RKMD analysis and demonstrate an integrated method for lipid annotation and chemical structure-based filtering for IMS datasets. Annotation of lipid features with lipid molecular class, radyl carbon chain length, and degree of unsaturation allows image reconstruction and visualization based on each structural characteristic. We show a proof-of-concept application of the method to a computationally generated IMS dataset and validate that the RKMD method is highly specific for lipid components in the presence of confounding background ions. Moreover, we demonstrate an application of the RKMD-based annotation and filtering to matrix-assisted laser desorption/ionization (MALDI) IMS lipidomic data from human kidney tissue analysis.

The human kidney is composed of many cell types that vary in their abundance and distribution from normal to diseased organ. As these cell types perform unique and essential functions, it is important to confidently label each within a single tissue to accurately assess tissue architecture and microenvironments. Towards this goal, we demonstrate the use of co-detection by indexing (CODEX) multiplexed immunofluorescence for visualizing 23 antigens within the human kidney. Using CODEX, many of the major cell types and substructures, such as collecting ducts, glomeruli, and thick ascending limb, were visualized within a single tissue section. Of these antibodies, 19 were conjugated in-house, demonstrating the flexibility and utility of this approach for studying the human kidney using custom and commercially available antibodies. We performed a pilot study that compared both fresh frozen and formalin-fixed paraffin-embedded healthy non-neoplastic and diabetic nephropathy kidney tissues. The largest cellular differences between the two groups was observed in cells labeled with aquaporin 1, cytokeratin 7, and α-smooth muscle actin. Thus, our data show the power of CODEX multiplexed immunofluorescence for surveying the cellular diversity of the human kidney and the potential for applications within pathology, histology, and building anatomical atlases.

PurposeCompare the ability of peripapillary and macular structural parameters, vascular parameters, and their integration to discriminate among glaucoma, suspected glaucoma (GS), and healthy controls (HCs).MethodsIn this study, 196 eyes of 119 patients with glaucoma (n = 81), patients with GS (n = 48), and HCs (n = 67) underwent optical coherence tomography (OCT) and OCT angiography to measure peripapillary retinal nerve fiber layer (pRNFL), macular ganglion cell-inner plexiform layer (mGCIPL) thicknesses, radial peripapillary capillary perfusion density (RPC-PD), and macular GCIPL perfusion density (GCIPL-PD). Parameters were integrated regionally with logistic regression and globally with machine learning algorithms. Diagnostic performances were evaluated with area under the receiver operating characteristic (AUROC) curves.ResultsPatients with glaucoma had mild to moderate damage (median, -3.3 dB; interquartile range, -6.5 to -1.4). In discriminating between patients with glaucoma and the HCs, pRNFL thickness had higher AUROC curve values than RPC-PD for average (0.87 vs. 0.62; P < 0.001), superior (0.86 vs. 0.54; P < 0.001), inferior (0.90 vs. 0.71; P < 0.001), and temporal (0.65 vs. 0.51; P = 0.02) quadrants. mGCIPL thickness had higher AUROC curve values than GCIPL-PD for average (0.84 vs. 0.68; P < 0.001), superotemporal (0.76 vs. 0.65; P = 0.016), superior (0.72 vs. 0.57; P = 0.004), superonasal (0.70 vs. 0.56; P = 0.01), inferotemporal (0.90 vs. 0.72; P < 0.001), inferior (0.87 vs. 0.69; P < 0.001), and inferonasal (0.78 vs. 0.65, P = 0.012) sectors. All structural multisector indices had higher diagnostic ability than vascular ones (P < 0.001). Combined structural-vascular indices did not outperform structural indices. Similar results were found to discriminate glaucoma from GS.ConclusionsCombining structural and vascular parameters in a structural-vascular index does not improve diagnostic ability over structural parameters alone.Translational relevanceOCT angiography does not add additional benefit to structural OCT in early to moderate glaucoma diagnosis.

PurposeWe compared rates of change of macular ganglion cell/inner plexiform (GCIPL) thickness and proportion of worsening and improving rates from 2 optical coherence tomography (OCT) devices in a cohort of eyes with glaucoma.DesignLongitudinal cohort study.MethodsIn a tertiary glaucoma clinic we evaluated 68 glaucoma eyes with ≥2 years of follow-up and ≥4 OCT images. Macular volume scans from 2 OCT devices were exported, coregistered, and segmented. Global and sectoral GCIPL data from the central 4.8 × 4.0-mm region were extracted. GCIPL rates of change were estimated with linear regression. Permutation analyses were used to control specificity with the 2.5 percentile cutoff point used to define "true" worsening. Main outcome measures included differences in global/sectoral GCIPL rates of change between 2 OCT devices and the proportion of negative vs positive rates of change (P < .05).ResultsAverage (standard deviation) 24-2 visual field mean deviation, median (interquartile range) follow-up time, and number of OCT images were -9.4 (6.1) dB, 3.8 (3.3-4.2) years, and 6 (5-8), respectively. GCIPL rates of thinning from Spectralis OCT were faster (more negative) compared with Cirrus OCT; differences were significant in superonasal (P = .03) and superotemporal (P = .04) sectors. A higher proportion of significant negative rates was observed with Spectralis OCT both globally and in inferotemporal/superotemporal sectors (P < .04). Permutation analyses confirmed the higher proportion of global and sectoral negative rates of change with Spectralis OCT (P < .001).ConclusionsChanges in macular GCIPL were detected more frequently on Spectralis' longitudinal volume scans than those of Cirrus OCT. OCT devices are not interchangeable with regard to detection of macular structural progression.

PurposeTo investigate differences across the visual field (VF) in the rate of glaucomatous progression, the likelihood of defect in four disease severity cross-sections, and comparisons of subgroups in each of between 12 demographic, comorbid, and clinical variables.MethodsTwo long-term glaucoma clinical trials used Humphrey Field Analyzer 24-2 VFs to calculate pointwise deviations from age-matched normal controls. Slopes of glaucomatous progression over time were calculated per participant using linear mixed models. Pointwise differences between subgroups in slopes and cross-sectional categories were tested, adjusting for multiple comparisons using false discovery rate (FDR) and Q values.ResultsPointwise data were available for 1118 patients who had 15,073 VFs. On average, defects were seen at all VF points. Of the 12 variables, six had average pointwise slopes where Subgroup 1 had significantly faster progression than Subgroup 2 at all or many of the 52 VF points: participants who were older (≥65 vs. younger), 52/52; were male, 13/52; had diabetes, 29/52; had hypertension, 46/52; had a larger cup-to-disc ratio (≥0.7), 36/52; or had larger differences in absolute mean deviation (MD) between eyes (>3 dB), 52/52. Cross-sectional patterns at MD severity of -12 to -6.1 dB showed strong midline effects for gender and other patterns for hypertension, cup-to-disc ratio, absolute difference in MD between eyes, and disc notching.ConclusionsThe approach used provides new longitudinal and cross-sectional insights into variation across the VF associated with demographic, comorbid, and clinical variables.Translational relevanceThis exploration and characterization of variable effects in the setting of pointwise VF testing may enable clinicians to anticipate patterns of VF loss based on demographic, comorbid, and clinical associations.

Here, we describe the preservation and preparation of human kidney tissue for interrogation by histopathology, imaging mass spectrometry, and multiplexed immunofluorescence. Custom image registration and integration techniques are used to create cellular and molecular atlases of this organ system. Through careful optimization, we ensure high-quality and reproducible datasets suitable for cross-patient comparisons that are essential to understanding human health and disease. Moreover, each of these steps can be adapted to other organ systems or diseases, enabling additional atlas efforts.

PurposeTo test the hypothesis that visual field (VF) progression can be predicted from baseline and longitudinal optical coherence tomography (OCT) structural measurements.DesignProspective cohort study.MethodsA total of 104 eyes (104 patients) with ≥3 years of follow-up and ≥5 VF examinations were enrolled. We defined VF progression based on pointwise linear regression on 24-2 VF (≥3 locations with slope less than or equal to -1.0 dB/year and P < .01). We used elastic net logistic regression (ENR) and machine learning to predict VF progression with demographics, baseline circumpapillary retinal nerve fiber layer (RNFL), macular ganglion cell/inner plexiform layer (GCIPL) thickness, and RNFL and GCIPL change rates at central 24 superpixels and 3 eccentricities, 3.4°, 5.5°, and 6.8°, from fovea and hemimaculas. Areas-under-ROC curves (AUC) were used to compare models.ResultsAverage ± SD follow-up and VF examinations were 4.5 ± 0.9 years and 8.7 ± 1.6, respectively. VF progression was detected in 23 eyes (22%). ENR selected rates of change of superotemporal RNFL sector and GCIPL change rates in 5 central superpixels and at 3.4° and 5.6° eccentricities as the best predictor subset (AUC = 0.79 ± 0.12). Best machine learning predictors consisted of baseline superior hemimacular GCIPL thickness and GCIPL change rates at 3.4° eccentricity and 3 central superpixels (AUC = 0.81 ± 0.10). Models using GCIPL-only structural variables performed better than RNFL-only models.ConclusionsVF progression can be predicted with clinically relevant accuracy from baseline and longitudinal structural data. Further refinement of proposed models would assist clinicians with timely prediction of functional glaucoma progression and clinical decision making.

Purpose/aimThe optic nerve (ON) becomes taut during adduction beyond ~26° in healthy people and patients with primary open angle glaucoma (POAG), but only retracts the globe in POAG. We used magnetic resonance imaging (MRI) to investigate this difference.Materials and methodsMRI was obtained in 2-mm quasi-coronal planes in central gaze, and smaller (~23-25°) and larger (~30-31°) adduction and abduction in 21 controls and 12 POAG subjects whose intraocular pressure never exceeded 21 mmHg. ON cross-sections were analyzed from the globe to 10 mm posteriorly. Area centroids were used to calculate ON path lengths and changes in cross-sections to calculate elongation assuming volume conservation.ResultsFor both groups, ON path was nearly straight (

PurposeDevelop a hierarchical longitudinal regression model for estimating local rates of change of macular ganglion cell complex (GCC) measurements with optical coherence tomography (OCT).MethodsWe enrolled 112 eyes with four or more macular OCT images and ≥2 years of follow-up. GCC thickness measurements within central 6 × 6 superpixels were extracted from macular volume scans. We fit data from each superpixel separately with several hierarchical Bayesian random-effects models. Models were compared with the Watanabe-Akaike information criterion. For our preferred model, we estimated population and individual slopes and intercepts (baseline thickness) and their correlation.ResultsMean (SD) follow-up time and median (interquartile range) baseline 24-2 visual field mean deviation were 3.6 (0.4) years and -6.8 (-12.2 to -4.3) dB, respectively. The random intercepts and slopes model with random residual variance was the preferred model. While more individual and population negative slopes were observed in the paracentral and papillomacular superpixels, superpixels in the superotemporal and inferior regions displayed the highest correlation between baseline thickness and rates of change (r = -0.43 to -0.50 for the top five correlations).ConclusionsA Bayesian linear hierarchical model with random intercepts/slopes and random variances is an optimal initial model for estimating GCC slopes at population and individual levels. This novel model is an efficient method for estimating macular rates of change and probability of glaucoma progression locally.Translational relevanceThe proposed Bayesian hierarchical model can be applied to various macular outcomes from different OCT devices and to superpixels of variable sizes to estimate local rates of change and progression probability.

PurposeTo compare local ganglion cell-inner plexiform layer (GCIPL) thickness measurements between 2 OCT devices and to explore factors that may influence the difference in measurements.DesignCross-sectional study.ParticipantsSixty-nine glaucoma eyes (63 patients) with evidence of central damage or mean deviation (MD) of -6.0 dB or worse on a 24-2 visual field (VF).MethodsCirrus and Spectralis OCT macular volume scans were exported, data from the central 20° of both OCT devices were centered and aligned, and 50 × 50 arrays of 0.4° × 0.4° superpixels were created. We estimated nonparametric (Spearman's) correlations and used Bland-Altman plots to compare GCIPL thickness measurements between the two OCTs at the superpixel level. Factors that may have influenced the differences between thickness measurements between the two devices were explored with linear mixed models.Main outcome measuresPooled and individual-eye Spearman's correlation and agreement between thickness measurements from the two devices.ResultsThe median 24-2 VF MD was -6.8 dB (interquartile range [IQR], -4.9 to -12.3 dB). The overall pooled Spearman's correlation between the two devices for all superpixels and eyes was 0.97 (P < 0.001). The median within-eye correlation coefficient was 0.72 (IQR, 0.59-0.79). Bland-Altman plots demonstrated a systematic bias in most individual eyes, with Spectralis GCIPL measurements becoming larger than Cirrus measurements with increasing superpixel thickness. The average superpixel thickness and distance to the fovea influenced the thickness difference between the two devices in multivariate models (P < 0.001).ConclusionsLocal macular thickness measurements from the Spectralis and Cirrus devices are highly correlated, but not interchangeable. Differences in thickness measurements between the two devices are influenced by the location of superpixels and their thickness.

Imaging mass spectrometry has become a mature molecular mapping technology that is used for molecular discovery in many medical and biological systems. While powerful by itself, imaging mass spectrometry can be complemented by the addition of other orthogonal, chemically informative imaging technologies to maximize the information gained from a single experiment and enable deeper understanding of biological processes. Within this review, we describe MALDI, SIMS, and DESI imaging mass spectrometric technologies and how these have been integrated with other analytical modalities such as microscopy, transcriptomics, spectroscopy, and electrochemistry in a field termed multimodal imaging. We explore the future of this field and discuss forthcoming developments that will bring new insights to help unravel the molecular complexities of biological systems, from single cells to functional tissue structures and organs.

Imaging mass spectrometry (IMS) technologies are capable of mapping a wide array of biomolecules in diverse cellular and tissue environments. IMS has emerged as an essential tool for providing spatially targeted molecular information due to its high sensitivity, wide molecular coverage, and chemical specificity. One of the major challenges for mapping the complex cellular milieu is the presence of many isomers and isobars in these samples. This challenge is traditionally addressed using orthogonal liquid chromatography (LC)-based analysis, though, common approaches such as chromatography and electrophoresis are not able to be performed at timescales that are compatible with most imaging applications. Ion mobility offers rapid, gas-phase separations that are readily integrated with IMS workflows in order to provide additional data dimensionality that can improve signal-to-noise, dynamic range, and specificity. Here, we highlight recent examples of ion mobility coupled to IMS and highlight their importance to the field.

With the advent of spectral-domain optical coherence tomography, imaging of the posterior segment of the eye can be carried out rapidly at multiple anatomical locations, including the optic nerve head, circumpapillary retinal nerve fiber layer, and macula. There is now ample evidence to support the role of spectral-domain optical coherence tomography imaging of the macula for detection of early glaucoma. Macular spectral-domain optical coherence tomography measurements demonstrate high reproducibility, and evidence on its utility for detection of glaucoma progression is accumulating. We present a comprehensive review of macular spectral-domain optical coherence tomography imaging emerging as an essential diagnostic tool in glaucoma.

PurposeTo use optical coherence tomography (OCT) to 3-dimensionally characterize the optic nerve head (ONH) in peripapillary scleral bowing in non-highly myopic healthy eyes.DesignCross-sectional, multicenter study.MethodsA total of 362 non-highly myopic (+6 diopters [D] > spherical equivalent > -6D) eyes of 362 healthy subjects from 20-90 years old underwent OCT ONH radial B-scan imaging. Bruch's membrane (BM), BM opening (BMO), anterior scleral canal opening (ASCO), and the peripapillary scleral surface were segmented. BMO and ASCO planes were fit, and their centroids, major axes, ovality, areas and offsets were determined. Peripapillary scleral bowing was characterized by 2 parameters: peripapillary scleral slope (ppSS) of 3 anterior peripapillary scleral segments (0-300, 300-700, and 700-1,000 μm from the ASCO centroid); and ASCO depth relative to a peripapillary scleral reference plane (ASCOD-ppScleral). Peripapillary choroidal thickness (ppCT) was calculated relative to the ASCO as the minimum distance between the anterior scleral surface and BM.ResultsBoth ppSS and ASCOD-ppScleral ranged from slightly inward through profoundly outward in direction. Both parameters increased with age and were independently associated with decreased ppCT.ConclusionsIn non-highly myopic healthy eyes, outward peripapillary scleral bowing achieved substantial levels, was markedly increased with age, and was independently associated with decreased peripapillary choroidal thickness. These findings provide a normative foundation for characterizing this anatomy in cases of high myopia and glaucoma and in eyes with optic disc tilt, torsion, and peripapillary atrophy.

PurposeTo investigate the relationship between longitudinal changes in macular thickness measurements from OCT and changes in central visual field (VF) in patients with glaucoma with central or advanced damage at baseline.DesignLongitudinal cohort study.ParticipantsA total of 116 eyes with ≥3 years of follow-up and ≥5 macular OCT images and central 10° VF tests were selected.MethodsOCT superpixels and VF locations were matched correcting for retinal ganglion cell (RGC) displacement. Superpixel thickness and VF total deviation (TD) values, in both logarithmic and linear scales, were averaged within 3 eccentricities (3.4°, 5.6°, and 6.8°) and superior and inferior hemiretinas and hemifields. We estimated pointwise TD rates of change and rates of change at superpixels for full macular thickness (FMT), ganglion cell complex (GCC), ganglion cell inner plexiform layer (GCIPL), and ganglion cell layer (GCL). Correlation of structure-function (SF) rates of change was investigated with parametric tests. We compared the proportion of worsening and positive slopes for superpixels and VF test locations (negative vs. positive rates of change with P < 0.05) throughout the follow-up period. Permutation analyses were used to control specificity.Main outcome measuresMagnitude of correlation between structural and functional rates of change and proportion of worsening and positive slopes as a function of follow-up time.ResultsThe median (interquartile range) follow-up and number of exams were 4.2 (3.7-4.6) years and 8 (7-9), respectively. The highest correlation of change rates was observed at 3.4° and 5.6° eccentricities (r = 0.24, 0.41, 0.40, and 0.40 for FMT, GCC, GCIPL, and GCL for 3.4° eccentricity and r = 0.28, 0.32, 0.31, and 0.32 for FMT, GCC, GCIPL, and GCL for 5.6° eccentricity, respectively). Although GCC measures demonstrated the highest overall longitudinal SF correlations, the differences were not statistically significant. Significant structural worsening was more frequently detected than functional deterioration at 3- and 5-year time points (P < 0.025). Permutation analyses also confirmed this finding.ConclusionsCorrelations between central structural and functional rates of change were weak to fair in this cohort. Structural changes were detected more frequently than functional changes. Measurements of both structure and function are required for optimal detection of central progression.

PurposeTopical prostaglandin analogs (PGAs) are common treatment for primary open-angle glaucoma (POAG) but reportedly may cause adnexal fat atrophy. We asked if patients with POAG treated with PGAs have abnormalities in orbital fat volume (OFV).MethodsWe studied 23 subjects with POAG who had never experienced intraocular pressure (IOP) exceeding 21 mm Hg and were treated long term with PGAs, in comparison with 21 age-matched controls. Orbital volume, non-fat orbital tissue volume, and OFV were measured using high-resolution magnetic resonance imaging.ResultsSubjects with POAG had been treated with PGAs for 39 ± 19 months (SD) and were all treated within the 4 months preceding study. In the region from trochlea to orbital apex, OFV in POAG was significantly less at 9.8 ± 1.9 mL than in the control subjects at 11.1 ± 1.3 mL (P = 0.019). However, between the globe-optic nerve junction (GONJ) and trochlea, OFV was similar in both groups. Width and cross sectional area of the bony orbit were significantly smaller in POAG than in controls (P < 0.0001). Posterior to the GONJ, the average orbital cross-sectional area was 68.2 mm2 smaller, and the orbital width averaged 1.5 mm smaller throughout the orbit, in patients with POAG than in controls.ConclusionsPatients with POAG who have been treated with PGAs have lower overall OFV than controls, but OFV in the anterior orbit is similar in both groups. Lower overall OFV in POAG may be a primary association of this disorder with a horizontally narrower bony orbit, which may be a risk factor for POAG at nonelevated IOPs.

Purpose/Aim: We used magnetic resonance imaging (MRI) to investigate effects of intraocular pressure (IOP), race, and other factors on optic nerve (ON) traction in adduction, a phenomenon proposed as neuropathic in open angle glaucoma (OAG).Materials and Methods: Thirty-five patients with OAG (26 with maximal untreated IOP ≤21 mmHg, 9 with IOP >21mmHg) and 48 controls underwent axial and quasi-coronal MRI in central gaze and large (27-33°) abduction and adduction. Some underwent MRI at smaller ductions (21-28°). Effects of presence vs. absence of OAG; within OAG whether maximum IOP level was ≤21 mmHg vs. >21 mmHg; adduction angle; race; age; and gender on ON path length and globe translation were analyzed using generalized estimating equations to account for possible intereye correlations of individual subjects.Results: Average visual field mean deviation (±standard error of mean, SEM) was -8.2 ± 1.2 dB in OAG with normal IOP, and -6.1 ± 1.4 in high IOP. In central gaze, ON path in OAG was significantly more redundant than in controls but in both groups the ON became significantly and almost equally straighter in small (~21°) or large (~27°) adduction than in central gaze. With progressive adduction only, globes retracted in OAG (P

PurposeTo assess anterior scleral canal opening (ASCO) offset relative to Bruch's membrane opening (BMO) (ASCO/BMO offset) so as to determine neural canal direction, obliqueness, and minimum cross-sectional area (NCMCA) in 362 healthy eyes.DesignCross-sectional study.MethodsAfter optical coherence tomography optic nerve head and retinal nerve fiber layer thickness (RNFLT) imaging, BMO and ASCO were manually segmented. Planes, centroids, size, and shape were calculated. Neural canal direction was defined by projecting the neural canal axis vector (connecting BMO and ASCO centroids) onto the BMO plane. Neural canal obliqueness was defined by the angle between the neural canal axis and the BMO plane perpendicular vector. NCMCA was defined by projecting BMO and ASCO points onto a neural canal axis perpendicular plane and measuring the area of overlap. The angular distance between superior and inferior peak RNFLT was measured, and correlations between RFNLT, BMO, ASCO, ASCO/BMO offset, and NCMCA were assessed.ResultsMean (SD) NCMCA was significantly smaller than either the BMO or ASCO area (1.33 (0.42), 1.82 (0.38), 2.22 (0.43) mm2, respectively), and most closely correlated to RNFLT (P < .001, R2 = 0.158). Neural canal direction was most commonly superior-nasal (55%). Mean neural canal obliqueness was 39.4° (17.3°). The angular distance between superior and inferior peak RNFLT correlated to neural canal direction (P ≤ .008, R2 = 0.093).ConclusionsASCO/BMO offset underlies neural canal direction, obliqueness, and NCMCA. RNFLT is more strongly correlated to NCMCA than to BMO or ASCO, and its peripapillary distribution is influenced by neural canal direction.

PurposeTo review central structure-function (SF) relationships in glaucoma; to compare contributions of within-session and between-session variability to total variability of macular optical coherence tomography (OCT) thickness measurements; and to test the hypothesis that longitudinal within-eye variability of central SF relationships is smaller than between-individual variability.MethodsWe reviewed the pertinent literature on central SF relationships in glaucoma. Thirty-eight eyes (20 normal or glaucoma subjects) had ×3 macular images per session over 3 sessions, and superpixels thickness measurements for ganglion cell layer (GCL), ganglion cell/inner plexiform layer (GCIPL), ganglion cell complex (GCC), and full macular thickness (FMT) were exported. Linear mixed models were used for estimating contributions of between- and within-session variability to total thickness variability. One hundred twenty eyes with ≥3 10° visual fields (VFs)/OCT images were enrolled for the longitudinal study. We investigated within-eye longitudinal SF relationships (GCIPL thickness vs VF total deviations) with a change-point regression model and compared within-eye to between-individual variabilities with components-of-variance models.ResultsIn the cross-sectional study, the between-session component contributed 8%, 11%, 11%, and 36% of total variability for GCL, GCIPL, GCC, and FMT, respectively. In the longitudinal study, between-individual variability explained 78%, 77%, and 67% of total SF variability at 3.4°, 5.6°, and 6.8° eccentricities, respectively (P < .05). SF relationships remained stable over time within individual eyes.ConclusionsWithin-session variability accounts for most of macular thickness variability over time. Longitudinal within-eye SF variability is smaller than between-individual variability. Study of within-eye SF relationships could help clinicians better understand SF linking in glaucoma and help refine progression algorithms. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.

Transformative technologies are enabling the construction of threedimensional (3D) maps of tissues with unprecedented spatial and molecularresolution. Over the next seven years, the NIH Common Fund Human BiomolecularAtlas Program (HuBMAP) intends to develop a widely accessible framework forcomprehensively mapping the human body at single-cell resolution by supportingtechnology development, data acquisition, and detailed spatial mapping. HuBMAPwill integrate its efforts with other funding agencies, programs, consortia,and the biomedical research community at large towards the shared vision of acomprehensive, accessible 3D molecular and cellular atlas of the human body, inhealth and various disease settings.

PurposeTo quantify peripapillary choroidal thickness (PCT) and the factors that influence it in healthy participants who represent the racial and ethnic composition of the U.S. population.MethodsA total of 362 healthy participants underwent optical coherence tomography (OCT) enhanced depth imaging of the optic nerve head with a 24 radial B-scan pattern aligned to the fovea to Bruch's membrane opening axis. Bruch's membrane, anterior scleral canal opening (ASCO), and the anterior scleral surface were manually segmented. PCT was measured at 100, 300, 500, 700, 900, and 1100 μm from the ASCO globally and within 12 clock-hour sectors. The effects of age, axial length, intraocular pressure, ethnicity, sex, sector, and ASCO area on PCT were assessed by ANOVA and univariable and multivariable regressions.ResultsGlobally, PCT was thicker further from the ASCO border and thinner with older age, longer axial length, larger ASCO area, European descent, and female sex. Among these effectors, age and axial length explained the greatest proportion of variance. The rate of age-related decline increased further from the ASCO border. Sectorally, the inferior-temporal sectors were thinnest (10.7%-20.0% thinner than the thickest sector) and demonstrated a higher rate of age-related loss (from 15.6% to 20.7% faster) at each ASCO distance.ConclusionsIn healthy eyes, PCT was thinnest in the inferior temporal sectors and thinner PCT was associated with older age, European descent, longer axial length, larger ASCO area, and female sex. Among these associations, age had the strongest influence, and its effect was greatest within the inferior temporal sectors.

PurposePrimary open-angle glaucoma (POAG) patients constitute a heterogenous group. Identification of phenotypic subtypes among these patients may provide a deeper understanding of the disease and aid associations with genotypes. We describe a phenotype of POAG patients associated with a constellation of systemic disorders; patients with this phenotype seem to be vulnerable to optic nerve damage at low intraocular pressures.Materials and methodsIn this retrospective study, we evaluated the medical records of active Jules Stein Eye Institute glaucoma patients from January 1996 to 2017 and included subjects with POAG, acquired pits of the optic nerve (APON), and at least one of the following: systolic blood pressure persistently ≤100 mm Hg, history of migraine headaches or migraine variant, and the Raynaud syndrome.ResultsOf 87 patients (125 eyes) with APON, 37 patients (55 eyes) met the study criteria. In total, 34 patients were female (92%). The median age at the time of diagnosis was 55 years. Nineteen patients (73%) had low systolic blood pressures, same number had Raynaud syndrome, and 25 (68%) had a history of migraine.ConclusionsWe describe a POAG subtype with APON and systemic vascular instability, predominantly female in their sixth decade of life who demonstrate progressive glaucomatous visual field damage at low intraocular pressure. We suggest that this clinical picture represents an important phenotype of POAG, and that identification and further study of it will help guide diagnosis and development of individualized treatments.

Rbpms (RNA-binding protein with multiple splicing) is a member of the RRM (RNA Recognition Motif) family of RNA-binding proteins, which is expressed as multiple alternatively spliced transcripts encoding different protein isoforms. We have shown earlier that Rbpms expression in the retina is restricted to retinal ganglion cells (RGCs), and have characterized this gene as a marker for RGCs. The aim of this study was to identify isoforms representing Rbpms in human retinas and to analyze its transcriptional regulation. We found that Rbpms is expressed as transcription variants 1 and 3 encoding isoforms A and C, respectively. These isoforms are encoded by the same first 6 exons but have different C-terminal ends encoded by exon 8 in variant 1 and exon 7 in variant 3. Computational analysis of the Rbpms 5' untranslated and flanking regions reveals the presence of three CpG islands and four predicted promoter regions (PPRs). The effect of PPR 1 (- 1672/- 1420) and PPR2 (- 330/- 79) on transcriptional activation was minimal, whereas PPR 3 (- 73/+ 177) and PPR4 (+ 274/+ 524) induced the expression by ~ 7 and ninefold compared to control, respectively. The maximum activity, a 30-fold increase above the control level, was obtained from the construct containing both PPRs 3 and 4. Site-directed mutagenesis of several cis-elements within PPR3 and PPR4 including five for Sp1, one for AP1, and two for NF-kB showed that mutation of the first three and especially the first GC box resulted in a threefold downregulation of gene expression. AP1, NF-kB, and two downstream Sp1 sites had no significant effect on expression level. The possible involvement of the GC box 1 at position - 54 in transcriptional regulation of Rbpms was corroborated by EMSA, which showed formation of a DNA-protein complex in the presence of the oligonucleotide corresponding to this Sp1-binding site.

PurposeTo determine the frequency with which retinal tissues other than the nerve fibre layer, hereafter referred to as protruded retinal layers (PRL), are a component of optical coherence tomography (OCT) neuroretinal rim measurements.MethodsNinety healthy (30 White, Black and Japanese, respectively) subjects were included in the study. A radial scan pattern (24 B-scans centred on Bruch's membrane opening [BMO]) was used. For each of the 48 minimum rim width (MRW) measurement points, we determined whether PRL were present, absent or indeterminate. When present, the proportion of PRL within the MRW was quantified.ResultsProtruded retinal layers were present in 503 (11.6%), absent in 3805 (88.1%) and indeterminate in 12 (0.3%) measurement points. Overall, 69 (76.6%) subjects had ≥1 points with PRL, with White subjects having the highest frequency and Japanese the lowest (29 [97%] and 18 [60%], respectively; p

Purpose:To quantify the influence of ocular and demographic factors on central laminar depth (LD) in healthy participants. Methods:A total of 362 normal subjects underwent optical coherence tomography (OCT) enhanced depth imaging of the optic nerve head (ONH) with a 24 radial B-scan pattern aligned to the fovea-to-Bruch's membrane opening (BMO) axis. BMO, anterior lamina, anterior scleral canal opening (ASCO), Bruch's membrane (BM), and the peripapillary scleral surface were manually segmented. The extent of laminar segmentation was quantified within 72 ASCO subsectors. Central LD was quantified relative to four reference planes: BMO, ASCO, BM, and scleral. The effects of age, sex, ethnicity, IOP, BMO area, ASCO area, and axial length on LD were assessed. Results:Laminar visibility was most consistent within the central ASCO (median 89%, range, 69%-95%). LDBMO and LDBM were significantly shallower in eyes with greater age, BMO area, and axial length and in females. LDASCO was shallower in eyes with greater ASCO area and axial length and in European and Hispanic descent compared to African descent eyes. LDSclera behaved similarly, but was not associated with axial length. BMO and ASCO area were not different between African descent and European descent eyes. Conclusions:Central LD was deeper in African descent eyes and influenced least by age, axial length, and sex, but more by ASCO area, when measured relative to the ASCO and sclera. However, the magnitude of these effects for all four reference planes was small, and their clinical importance in the detection of glaucoma and its progression remains to be determined.

PurposeTo test the hypotheses that: (1) structure-function (SF) relationships between visual fields (VF) and Bruch's membrane opening-based minimum rim width (BMO-MRW) measurements are superior to those for peripapillary retinal nerve fiber layer (pRNFL) in perimetric glaucoma; (2) BMO-MRW measurements may extend the utility of structural measurement across the range of glaucoma severity; and (3) to estimate the influence of Bruch's membrane opening (BMO) size on BMO-MRW measurements.MethodsOne hundred eight perimetric glaucoma eyes (68 patients) with good quality spectral-domain optical coherence tomography images of the optic disc and pRNFL, and reliable VF within 6 months were recruited. Relationship of global and sectoral BMO-MRW and pRNFL thickness with corresponding VF parameters and the influence of normalizing BMO-MRW (on BMO circumference, nBMO-MRW) on SF relationships were investigated. Broken-stick models were used to compare the point at which pRNFL and BMO-MRW parameters reached their measurement floor.ResultsThe median (interquartile range) of VF mean deviation was -5.9 (-12.6 to -3.6) dB. Spearman correlation coefficients between pRNFL, BMO-MRW, and nBMO-MRW measures and corresponding VF cluster average deviations ranged between 0.55 to 0.80, 0.35 to 0.66, and 0.38 to 0.65, respectively. Bruch's membrane opening-MRW parameters demonstrated weaker SF relationships compared with pRNFL globally and in temporal, temporal-superior, and nasal-inferior sectors (P < 0.03). Normalization of BMO-MRW did not significantly influence SF relationships.ConclusionsStructure-function relationships were somewhat weaker with BMO-MRW parameters compared with pRNFL in eyes with perimetric glaucoma. Bruch's membrane opening-MRW normalization did not significantly change SF relationships in this group of eyes with mild departures from average BMO size.

PurposeTo test the hypothesis that vertical asymmetry in macular ganglion cell/inner plexiform layer (GCIPL) thickness can improve detection of early glaucoma.MethodsSixty-nine normal eyes and 101 glaucoma eyes had macular imaging with spectral-domain optical coherence tomography (OCT; 200 × 200 cube). The resulting GCIPL thickness matrix was grouped into a 20 × 20 superpixel array and superior superpixels were compared to their inferior counterparts. A global asymmetry index (AI) was defined as the grand mean of the asymmetry ratios. To measure local asymmetry, the corresponding thickness measurements of three rows above and below the horizontal raphe were compared individually and in combinations. Global and local AIs were compared to the best-performing GCIPL thickness parameters with area under the receiver operating curves (AUC) and sensitivity/specificities.ResultsAge or axial length did not influence AIs in normal subjects (P ≥ 0.08). Global and local AIs were significantly higher in the glaucoma group compared to normal eyes. Minimum (AUC = 0.962, 95% confidence interval [CI]: 0.936-0.989) and inferotemporal thickness (AUC = 0.944, 95% CI: 0.910-0.977; P = 0.122) performed best for detection of early glaucoma. The AUC for global AI was 0.851 (95% CI: 0.792-0.909) compared to 0.916 (95% CI: 0.874-0.958) for the best local AI. Combining minimum or inferotemporal GCIPL thickness and the best local AI led to higher partial AUCs (0.088 and 0.085, 90% specificity, P = 0.120 and 0.130, respectively) than GCIPL thickness measures.ConclusionsMacular vertical thickness asymmetry measures did not perform better than sectoral or minimum GCIPL thickness for detection of early glaucoma. Combining local asymmetry parameters with the best sectoral GCIPL thickness measures enhanced this task.

PurposeWe used magnetic resonance imaging (MRI) to ascertain effects of optic nerve (ON) traction in adduction, a phenomenon proposed as neuropathic in primary open-angle glaucoma (POAG).MethodsSeventeen patients with POAG and maximal IOP ≤ 20 mm Hg, and 31 controls underwent MRI in central gaze and 20° to 30° abduction and adduction. Optic nerve and sheath area centroids permitted computation of midorbital lengths versus minimum paths.ResultsAverage mean deviation (±SEM) was -8.2 ± 1.2 dB in the 15 patients with POAG having interpretable perimetry. In central gaze, ON path length in POAG was significantly more redundant (104.5 ± 0.4% of geometric minimum) than in controls (102.9 ± 0.4%, P = 2.96 × 10-4). In both groups the ON became significantly straighter in adduction (28.6 ± 0.8° in POAG, 26.8 ± 1.1° in controls) than central gaze and abduction. In adduction, the ON in POAG straightened to 102.0% ± 0.2% of minimum path length versus 104.5% ± 0.4% in central gaze (P = 5.7 × 10-7), compared with controls who straightened to 101.6% ± 0.1% from 102.9% ± 0.3% in central gaze (P = 8.7 × 10-6); and globes retracted 0.73 ± 0.09 mm in POAG, but only 0.07 ± 0.08 mm in controls (P = 8.8 × 10-7). Both effects were confirmed in age-matched controls, and remained significant after correction for significant effects of age and axial globe length (P = 0.005).ConclusionsAlthough tethering and elongation of ON and sheath are normal in adduction, adduction is associated with abnormally great globe retraction in POAG without elevated IOP. Traction in adduction may cause mechanical overloading of the ON head and peripapillary sclera, thus contributing to or resulting from the optic neuropathy of glaucoma independent of IOP.

PurposeTo test the hypothesis that structural and functional measures predict contrast sensitivity (CS) outcomes in glaucomatous eyes.DesignCross-sectional prospective study.MethodsOne hundred five eyes of 65 patients who underwent macular spectral-domain optical coherence tomography imaging, 24-2 standard achromatic visual fields (VF), and CS measurement on the same day were enrolled. Association of CS at 4 spatial frequencies (3, 6, 12, and 18 cycles per degree, cpd) with structural and functional outcomes was explored with correlation and regression analyses.ResultsThe median (IQR) 24-2 visual field mean deviation was -7.6 (-11.1 to -3.0). Significant correlations were found between CS at 6 cpd and ganglion cell/inner plexiform layer thickness at inferotemporal and inferonasal macular sectors (ρ = 0.222, P = .023 and ρ = 0.209, P = .032, respectively). CS at 6 cpd demonstrated higher correlations with full macular thickness measurements, the strongest of which was with the central macular thickness in the superior 6 × 3-degree region (ρ = 0.311, P = .001). Contrast sensitivity at 6 cpd also had the strongest correlation with mean deviation of the 4 central VF points (ρ = -0.420; P < .001). There was a significant correlation between logMAR visual acuity and contrast sensitivity at 6, 12, and 18 cpd (ρ = -0.306, ρ = -0.348 and ρ = -0.241, P < .013, respectively).ConclusionsStructural and functional measures showed a fair relationship with contrast sensitivity. This association was most prominent between full-thickness macular measures or central VF parameters and CS at 6 cpd. Contrast sensitivity was not a reliable surrogate for glaucoma severity in this cross-sectional study.

BackgroundAqueous shunts are employed to control intraocular pressure (IOP) for people with primary or secondary glaucomas who fail or are not candidates for standard surgery.ObjectivesTo assess the effectiveness and safety of aqueous shunts for reducing IOP in glaucoma compared with standard surgery, another type of aqueous shunt, or modification to the aqueous shunt procedure.Search methodsWe searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (2016, Issue 8), MEDLINE Ovid (1946 to August 2016), Embase.com (1947 to August 2016), PubMed (1948 to August 2016), LILACS (Latin American and Caribbean Health Sciences Literature Database) (1982 to August 2016), ClinicalTrials.gov (www.clinicaltrials.gov); searched 15 August 2016, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en); searched 15 August 2016. We did not use any date or language restrictions in the electronic search for trials. We last searched the electronic databases on 15 August 2016. We also searched the reference lists of identified trial reports and the Science Citation Index to find additional trials.Selection criteriaWe included randomized controlled trials that compared various types of aqueous shunts with standard surgery or to each other in eyes with glaucoma.Data collection and analysisTwo review authors independently screened search results for eligibility, assessed the risk of bias, and extracted data from included trials. We contacted trial investigators when data were unclear or not reported. We graded the certainty of the evidence using the GRADE approach. We followed standard methods as recommended by Cochrane.Main resultsWe included 27 trials with a total of 2099 participants with mixed diagnoses and comparisons of interventions. Seventeen studies reported adequate methods of randomization, and seven reported adequate allocation concealment. Data collection and follow-up times varied.Four trials compared an aqueous shunt (Ahmed or Baerveldt) with trabeculectomy, of which three reported one-year outcomes. At one-year, the difference in IOP between aqueous shunt groups and trabeculectomy groups was uncertain (mean difference (MD) 2.55 mmHg, 95% confidence interval (CI) -0.78 to 5.87; 380 participants; very low-certainty evidence). The difference in logMAR visual acuity was also uncertain (MD 0.12 units, 95% CI -0.07 to 0.31; 380 participants; very low-certainty evidence). In two trials, the difference in visual field score was uncertain (MD -0.25, 95% CI -1.91 to 1.40; 196 participants; very low-certainty evidence). The mean number of antiglaucoma medications was higher in the aqueous shunt group than the trabeculectomy group in one trial (MD 0.80, 95% CI 0.48 to 1.12; 184 participants; low-certainty evidence). The effect on needing additional glaucoma surgery was uncertain between groups in two trials (risk ratio (RR) 0.24, 95% CI 0.04 to 1.36; 329 participants; very low-certainty evidence). In one trial, fewer total adverse events were reported in the aqueous shunt group than the trabeculectomy group (RR 0.59, 95% CI 0.43 to 0.81; 212 participants; very low-certainty evidence). No trial reported quality-of-life outcomes at one-year follow-up.Two trials that compared the Ahmed implant with the Baerveldt implant for glaucoma found higher mean IOP in the Ahmed group at one-year follow-up (MD 2.60 mmHg, 95% CI 1.58 to 3.62; 464 participants; moderate-certainty evidence). The difference in logMAR visual acuity was uncertain between groups (MD -0.07 units, 95% CI -0.27 to 0.13; 501 participants; low-certainty evidence). The MD in number of antiglaucoma medications was within one between groups (MD 0.35, 95% CI 0.11 to 0.59; 464 participants; moderate-certainty evidence). More participants in the Ahmed group required additional glaucoma surgery than the Baerveldt group (RR 2.77, 95% CI 1.02 to 7.54; 514 participants; moderate-certainty evidence). The two trials reported specific adverse events but not overall number of adverse events. Neither trial reported visual field or quality-of-life outcomes at one-year follow-up.One trial compared the Ahmed implant with the Molteno implant for glaucoma over two-year follow-up. Mean IOP was higher in the Ahmed group than the Molteno group (MD 1.64 mmHg, 95% CI 0.85 to 2.43; 57 participants; low-certainty evidence). The differences in logMAR visual acuity (MD 0.08 units, 95% CI -0.24 to 0.40; 57 participants; very low-certainty evidence) and mean deviation in visual field (MD -0.18 dB, 95% CI -3.13 to 2.77; 57 participants; very low-certainty evidence) were uncertain between groups. The mean number of antiglaucoma medications was also uncertain between groups (MD -0.38, 95% CI -1.03 to 0.27; 57 participants; low-certainty evidence). The trial did not report the proportion needing additional glaucoma surgery, total adverse events, or quality-of-life outcomes.Two trials compared the double-plate Molteno implant with the Schocket shunt for glaucoma; one trial reported outcomes only at six-month follow-up, and the other did not specify the follow-up time. At six-months, mean IOP was lower in the Molteno group than the Schocket group (MD -2.50 mmHg, 95% CI -4.60 to -0.40; 115 participants; low-certainty evidence). Neither trial reported the proportion needing additional glaucoma surgery, total adverse events, or visual acuity, visual field, or quality-of-life outcomes.The remaining 18 trials evaluated modifications to aqueous shunts, including 14 trials of Ahmed implants (early aqueous suppression versus standard medication regimen, 2 trials; anti-vascular endothelial growth factor agent versus none, 4 trials; corticosteroids versus none, 2 trials; shunt augmentation versus none, 3 trials; partial tube ligation versus none, 1 trial; pars plana implantation versus conventional implantation, 1 trial; and model M4 versus model S2,1 trial); 1 trial of 500 mm2 Baerveldt versus 350 mm2 Baerveldt; and 3 trials of Molteno implants (single-plate with oral corticosteroids versus single-plate without oral corticosteroids, 1 trial; double-plate versus single-plate, 1 trial; and pressure-ridge versus double-plate with tube ligation, 1 trial).Authors' conclusionsInformation was insufficient to conclude whether there are differences between aqueous shunts and trabeculectomy for glaucoma treatment. While the Baerveldt implant may lower IOP more than the Ahmed implant, the evidence was of moderate-certainty and it is unclear whether the difference in IOP reduction is clinically significant. Overall, methodology and data quality among existing randomized controlled trials of aqueous shunts was heterogeneous across studies, and there are no well-justified or widely accepted generalizations about the superiority of one surgical procedure or device over another.

PurposeWe tested the hypothesis that the macular ganglion cell layer (GCL) thickness demonstrates a stronger structure-function (SF) relationship and extends the useful range of macular measurements compared with combined macular inner layer or full thickness.MethodsNinety-eight glaucomatous eyes and eight normal eyes with macular spectral domain optical coherence tomography (SD-OCT) volume scans and 10-2 visual fields were enrolled. Inner plexiform layer (IPL), GCL, macular retinal nerve fiber layer (mRNFL), ganglion cell-inner plexiform layer (GCIPL), ganglion cell complex (GCC), and full thickness (FT) measurements were calculated for 8 × 8 arrays of 3° superpixels. Main outcome measures were local structure-function relationships between macular superpixels and corresponding sensitivities on 10-2 fields after adjusting for ganglion cell displacement, dynamic range of measurements, and the change point (total deviation value where macular parameters reached measurement floor).ResultsMedian (interquartile range [IQR]) mean deviation was -7.2 (-11.6 to -3.2) dB in glaucoma eyes. Strength of SF relationships was highest for GCIPL, GCL, GCC, and IPL (ρ = 0.635, 0.627, 0.621, and 0.577, respectively; P ≤ 0.046 for comparisons against GCIPL). Highest SF correlations coincided with the peak of GCL thickness, where the dynamic range was widest for FT (81.1 μm), followed by GCC (65.7 μm), GCIPL (54.9 μm), GCL (35.2 μm), mRNFL (27.5 μm), and IPL (20.9 μm). Change points were similar for all macular parameters (-7.8 to -8.9 dB).ConclusionsGCIPL, GCL, and GCC demonstrated comparable SF relationships while FT, GCC, and GCIPL had the widest dynamic range. Measurement of GCL did not extend the range of useful structural measurements. Measuring GCL does not provide any advantage for detection of progression with current SD-OCT technology.

PurposeTo evaluate tonometric outcomes of patients with primary angle closure glaucoma (PACG) who have undergone trabeculectomy with mitomycin C (MMC) with and without concurrent phacoemulsification and to identify risk factors for postoperative failure.Patients and methodsRetrospective cohort study of 44 eyes of 33 phakic patients who underwent trabeculectomy with MMC with or without combined phacoemulsification for PACG. The primary endpoint was qualified tonometric success at 12 months according to predefined criteria. LogMAR visual acuity, number of glaucoma medications, and postoperative complications were also evaluated. Cox proportional hazard regression analysis was performed to identify potential risk factors for trabeculectomy failure.ResultsMean intraocular pressure (IOP) decreased from 21.3±7.9 to 12.2±3.9 mm Hg at 12 months (P1 minute were associated with decreased risk of surgical failure. Concurrent phacoemulsification at the time of trabeculectomy did not alter tonometric success or rate of complications.ConclusionsIn phakic patients with PACG, trabeculectomy with MMC significantly reduces IOP and number of glaucoma medications at 12 months without change in visual acuity. However, success rates are modest when based on more demanding tonometric criteria.

Heat shock proteins (HSPs) belong to a superfamily of stress proteins that are critical constituents of a complex defense mechanism that enhances cell survival under adverse environmental conditions. Cell protective roles of HSPs are related to their chaperone functions, antiapoptotic and antinecrotic effects. HSPs' anti-apoptotic and cytoprotective characteristics, their ability to protect cells from a variety of stressful stimuli, and the possibility of their pharmacological induction in cells under pathological stress make these proteins an attractive therapeutic target for various neurodegenerative diseases; these include Alzheimer's, Parkinson's, Huntington's, prion disease, and others. This review discusses the possible roles of HSPs, particularly HSP70 and small HSPs (alpha A and alpha B crystallins) in enhancing the survival of retinal ganglion cells (RGCs) in optic neuropathies such as glaucoma, which is characterized by progressive loss of vision caused by degeneration of RGCs and their axons in the optic nerve. Studies in animal models of RGC degeneration induced by ocular hypertension, optic nerve crush and axotomy show that upregulation of HSP70 expression by hyperthermia, zinc, geranyl-geranyl acetone, 17-AAG (a HSP90 inhibitor), or through transfection of retinal cells with AAV2-HSP70 effectively supports the survival of injured RGCs. RGCs survival was also stimulated by overexpression of alpha A and alpha B crystallins. These findings provide support for translating the HSP70- and alpha crystallin-based cell survival strategy into therapy to protect and rescue injured RGCs from degeneration associated with glaucomatous and other optic neuropathies.

PurposeWe tested the hypotheses that the mismatch between the clinical disc margin (CDM) and Bruch's membrane opening (BMO) is a function of BMO area (BMOA) and is affected by the presence of glaucoma.MethodsA total of 45 normal eyes (45 subjects) and 53 glaucomatous eyes (53 patients) were enrolled and underwent radial optic nerve head (ONH) imaging with spectral domain optical coherence tomography. The inner tip of the Bruch's membrane (BM) and the clinical disc margin were marked on radial scans and optic disc photographs, and were coregistered with custom software. The main outcome measure was the difference between the clinical disc area (CDA) and BMOA, or CDA-BMOA mismatch, as a function of BMOA and diagnosis. Multivariate regression analyses were used to explore the influence of glaucoma and BMOA on the mismatch.ResultsGlobal CDA was larger than BMOA in both groups but the difference was statistically significant only in the normal group (1.98 ± 0.37 vs. 1.85 ± 0.45 mm2, P = 0.02 in the normal group; 1.96 ± 0.38 vs. 1.89 ± 0.56 mm2, P = 0.08 in the glaucoma group). The sectoral CDA-BMOA mismatch was smaller in superotemporal (P = 0.04) and superonasal (P = 0.05) sectors in the glaucoma group. The normalized CDA-BMOA difference decreased with increasing BMOA in both groups (P < 0.001). Presence or severity of glaucoma did not affect the CDA-BMOA difference (P > 0.14).ConclusionsClinical disc area was larger than BMOA in normal and glaucoma eyes but reached statistical significance only in the former group. The CDA-BMOA mismatch diminished with increasing BMOA but was not affected by presence of glaucoma. These findings have important clinical implications regarding clinical evaluation of the ONH.

PurposeTo describe the location of initial visual field defects (VFD) in glaucoma, their modes of deterioration, and those factors associated with different modes of deterioration.MethodsPatients with POAG were categorized into four groups based on three consecutive initial VFD: (1) superior paracentral defects (PD), (2) inferior PD, (3) superior nasal defects (ND), and (4) inferior ND. According to the worsening of the VF, four further subgroups were identified: (1) superior central worsening (CW), (2) inferior CW, (3) superior peripheral or nasal worsening (NW), and (4) inferior NW. Systemic and ocular factors were analyzed for each of the subgroups to identify possible associations.ResultsOne hundred sixty-two eyes of 162 subjects were analyzed. Superior PD (n = 40) were more frequent in females and associated with disc hemorrhage (DH), and were less frequent in patients with systemic hypertension (HT). Inferior PD (n = 35) showed a significant association with cup shape measure and axial length. Superior ND (n = 37) were more highly associated with HT and diabetes. Inferior ND (n = 50) showed a lower incidence of DH. With binary logistic regression analysis, superior PD showed a significant association with both HT and DH. With respect to VF worsening, superior CW showed a significant association with HT and diabetes, whereas superior NW was associated with a high minimum IOP during follow-up, and inferior NW was associated with a high maximum IOP during follow-up.ConclusionsThe initial location and subsequent direction of worsening of VFD were associated with different systemic and ocular factors.

We evaluated the effect of AAV2- and 17-AAG (17-N-allylamino-17-demethoxygeldanamycin)-mediated upregulation of Hsp70 expression on the survival of retinal ganglion cells (RGCs) injured by optic nerve crush (ONC). AAV2-Hsp70 expression in the retina was primarily observed in the ganglion cell layer. Approximately 75% of all transfected cells were RGCs. RGC survival in AAV2-Hsp70-injected animals was increased by an average of 110% 2 weeks after the axonal injury compared with the control. The increase in cell numbers was not even across the retinas with a maximum effect of approximately 306% observed in the inferior quadrant. 17-AAG-mediated induction of Hsp70 expression has been associated with cell protection in various models of neurodegenerative diseases. We show here that a single intravitreal injection of 17-AAG (0.2 ug ul(-1)) results in an increased survival of ONC-injured RGCs by approximately 49% compared with the vehicle-treated animals. Expression of Hsp70 in retinas of 17-AAG-treated animals was upregulated approximately by twofold compared with control animals. Our data support the idea that the upregulation of Hsp70 has a beneficial effect on the survival of injured RGCs, and the induction of this protein could be viewed as a potential neuroprotective strategy for optic neuropathies.

PurposeTo examine the prevalence of visual field deterioration in contralateral eyes of patients with worsening open-angle glaucoma and to evaluate the spatial concordance of visual field deterioration between both eyes.MethodsOne hundred sixteen open-angle glaucoma patients who underwent 8 or more visual field examinations over ≥ 6 years of follow-up were included. The rates of the fast and slow components of visual field decay for each of 52 visual field test locations were calculated with point-wise exponential regression analysis. The spatial concordance of visual field deterioration in contralateral eyes was evaluated with a concordance ratio (calculated as the number of overlapping locations divided by the total number of deteriorating locations) and by comparing the rate of decay in corresponding modified glaucoma hemifield test clusters.ResultsThe average visual field mean deviation (± standard deviation [SD]) was -8.5 (± 6.4) dB and the mean (± SD) follow-up time was 9.0 (± 1.6) years. Sixty-three patients had mild damage, 23 had moderate damage, and 30 had severe damage. The mean concordance ratio (± SD) was 0.46 (± 0.32) for the mild group, 0.33 (± 0.27) for the moderate group, and 0.35 (± 0.21) for the severe group. Thirty-one patients (27%) had deterioration in concordant locations (p < 0.05). Visual field deterioration was greater in the superior hemifield than the inferior hemifield (p < 0.05) when evaluated with both the concordance ratio and modified glaucoma hemifield test cluster analysis methods.ConclusionsThere is only fair spatial concordance with regard to visual field deterioration between the both eyes of an individual. We conclude that testing algorithms taking advantage of inter-eye spatial concordance would not be particularly advantageous in the early detection of glaucomatous deterioration.