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Purpose: To compare rim area rates in patients with and without the visual field (VF) progression endpoint in the Canadian Glaucoma Study and determine whether intraocular pressure (IOP) reduction following the endpoint altered rim area rate., Design: Prospective multicenter cohort study., Methods: setting: University hospitals., Patient Population: Two hundred and six patients with open-angle glaucoma were examined at 4-month intervals with standard automated perimetry and confocal scanning laser tomography., Intervention: After the endpoint, IOP was reduced by ≥20%., Outcome Measures: Univariate analysis for change in rim area rate and multivariable analysis to adjust for independent covariates (eg, age, sex, and IOP)., Results: Patients with an endpoint (n = 59) had a worse rim area rate prior to the endpoint compared to those without (n = 147; median [interquartile range]: -14 [-32, 11] × 10(-3) mm(2)/y and -5 [-14, 5] × 10(-3) mm(2)/y, respectively, P = .02). In univariate analysis, there was no difference in rim area rate before and after the endpoint (median difference [95% CI], 8 (-10, 24) × 10(-3) mm(2)/y), but the muItivariate analysis showed that IOP reduction >2 mm Hg after the endpoint was strongly linked to a reduction in rim area rate decline (8 × 10(-3) mm(2)/y for each additional 1 mm Hg reduction)., Conclusions: Patients with a VF endpoint had a median rim area rate that was nearly 3 times worse than those without an endpoint. Lower mean follow-up IOP was independently associated with a slower decline in rim area., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: To quantify and characterize the difference between automated and manual segmentation of optic nerve head structures with spectral-domain optical coherence tomography (SD-OCT)., Methods: Optic nerve head radial scans in 107 glaucoma patients and 48 healthy controls were conducted with SD-OCT. Independent segmentations of the internal limiting membrane (ILM) and Bruch's membrane opening (BMO) were performed manually with custom software and with an automated algorithm in each radial scan. The minimum distance between BMO and ILM, termed BMO-minimum rim width (BMO-MRW) was calculated with each segmentation method. Absolute differences between automated and manual segmentations of ILM (ΔILM) and BMO (ΔBMO), and the resulting computation of BMO-MRW (ΔBMO-MRW) were computed. Finally, the relationship between image quality score and ΔILM and ΔBMO was explored., Results: The median (interquartile range, IQR) ΔILM was 8.9 (6.5, 13.4) μm in patients and 7.3 (5.3, 9.9) μm in controls. The corresponding values for ΔBMO were 11.5 (6.6, 22.1) μm and 12.4 (6.8, 25.4) μm. Subject-averaged ΔILM was higher in patients than controls (P < 0.01); however, mean ΔBMO was not (P = 0.09). The median (IQR) subject-averaged absolute ΔBMO-MRW was 13.4 (10.6, 16.8) μm in patients and 12.1 (10.0, 16.8) μm in controls and not statistically different (P = 0.21). Mean image quality score was statistically higher in controls than patients (P = 0.03) but not related to subject-averaged ΔILM or ΔBMO., Conclusions: In individual scans, the median difference in ILM and BMO segmentations was <2 and <3 image pixels, respectively. There were no differences between patients and controls in ΔBMO-MRW.

Purpose: To investigate the agreement between neuroretinal rim area (RA) measurements using the Heidelberg Retina Tomograph I (HRT Classic) and Heidelberg Retina Tomograph II (HRT II). To compare apparent RA changes in follow-up series of HRT II topographies when using either an HRT Classic or HRT II mean topography as baseline., Design: Cross-sectional study and "no-change," short time series study., Participants: Forty-three ocular hypertensive and 31 primary open angle glaucoma subjects., Methods: Five HRT Classic and 5 HRT II examinations were acquired from 1 eye of each subject, across 2 visits within 6 weeks. For the cross-sectional study, follow-up RA measurements from HRT Classic and HRT II were compared, using the same HRT Classic mean topography as the baseline. The linear rates of RA change were compared in 2 short time series with either an HRT Classic or an HRT II mean topography as baseline, and 4 follow-up HRT II mean topographies. Intervals between topographies were arbitrarily set at 1 year for meaningful comparisons of rates. Rates of RA change over time were calculated by linear regression. Separate analyses were performed using 3 available reference planes (RP)., Main Outcome Measures: Global and sectoral RA measurements in HRT Classic and HRT II mean topographies; linear rates of RA change., Results: HRT Classic minus HRT II mean differences (95% limits of agreement) were 0.09 (-0.17, 0.35) mm, 0.09 (-0.13, 0.32) mm, and 0.11 (-0.24, 0.46) mm for the Moorfields, 320 µm, and standard RPs, respectively (P<0.001 for all RPs, Wilcoxon rank sum test). In the time series, the mean differences (95% limits of agreement) of RA rates of change (HRT Classic baseline minus HRT II baseline) were -0.01 (-0.06, 0.03) mm/y, -0.01 (-0.06, 0.04) mm/y, and -0.0 (-0.09, 0.05) mm/y using the Moorfields, 320 µm, and standard RPs, respectively., Conclusion: Although HRT software is backward-compatible, follow-up RA measurements made in the same eye using HRT Classic and HRT II devices display statistically and clinically meaningful systematic differences when HRT Classic topographies are used as a baseline.

Objective: Neuroretinal rim assessment based on the clinical optic disc margin (DM) lacks a sound anatomic basis for 2 reasons: (1) The DM is not reliable as the outer border of rim tissue because of clinically and photographically invisible extensions of Bruch's membrane (BM) inside the DM and (2) nonaccountability of rim tissue orientation in the optic nerve head (ONH). The BM opening-minimum rim width (BMO-MRW) is a parameter that quantifies the rim from its true anatomic outer border, BMO, and accounts for its variable orientation. We report the diagnostic capability of BMO-MRW., Design: Case control., Participants: Patients with open-angle glaucoma (n = 107) and healthy controls (n = 48)., Methods: Spectral-domain optical coherence tomography (SD-OCT) with 24 radial and 1 circumpapillary B-scans, centered on the ONH, and confocal scanning laser tomography (CSLT) were performed. The internal limiting membrane (ILM) and BMO were manually segmented in each radial B-scan. Three SD-OCT parameters were computed globally and sectorally: (1) circumpapillary retinal nerve fiber layer thickness (RNFLT); (2) BMO-horizontal rim width (BMO-HRW), the distance between BMO and ILM in the BMO reference plane; and (3) BMO-MRW, the minimum distance between BMO and ILM. Moorfields Regression Analysis (MRA) with CLST was performed globally and sectorally to yield MRA1 and MRA2, where "borderline" was classified as normal and abnormal, respectively., Main Outcome Measures: Sensitivity, specificity, and likelihood ratios (LRs) for positive and negative test results (LR+/LR-)., Results: The median (interquartile range) age and mean deviation of patients and controls were 69.9 (64.3-76.9) and 65.0 (58.1-74.3) years and -3.92 (-7.87 to -1.62) and 0.33 (-0.32 to 0.98) dB, respectively. Globally, BMO-MRW yielded better diagnostic performance than the other parameters. At 95% specificity, the sensitivity of RNFLT, BMO-HRW, and BMO-MRW was 70%, 51%, and 81%, respectively. The corresponding LR+/LR- was 14.0/0.3, 10.2/0.5, and 16.2/0.2. Sectorally, at 95% specificity, the sensitivity of RNFLT ranged from 31% to 59%, of BMO-HRW ranged from 35% to 64%, and of BMO-MRW ranged from 54% to 79%. Globally and in all sectors, BMO-MRW performed better than MRA1 or MRA2., Conclusions: The higher sensitivity at 95% specificity in early glaucoma of BMO-MRW compared with current BMO methods is significant, indicating a new structural marker for the detection and risk profiling of glaucoma., (Copyright © 2013 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To study changes in lamina cribrosa position and prelaminar tissue thickness (PTT) after surgical IOP reduction in glaucoma patients., Methods: Twenty-two patients (mean age, 71.4 years) were imaged with spectral domain optical coherence tomography (SD-OCT; 24 radial B-scans centered on the optic nerve head [ONH]) before trabeculectomy or tube shunt implantation. Follow up images were acquired 1 week, 1 month, 3 months, and 6 months postsurgery. Bruch's membrane opening (BMO), the internal limiting membrane (ILM) and the anterior laminar surface (ALS) were segmented in each radial scan with custom software. Surfaces were fitted to the ILM and ALS with the extracted three-dimesional coordinates. PTT was the distance between the ILM and ALS, perpendicular to a BMO reference plane. Serial postsurgical laminar displacement (LD), relative to the BMO reference plane, and changes in PTT were measured. Positive values indicated anterior LD., Results: Mean (SD) presurgery IOP was 18.1 (6.5) mm Hg, and reduced by 4.7 (5.5), 2.4 (7.7), 7.0 (6.2), and 6.8 (7.5) mm Hg at 1 week, 1 month, 3 months, and 6 months postsurgery, respectively. At the four postsurgery time points, there was significant anterior LD (1.8 [9.5], -1.1 [8.9], 8.8 [20.2], and 17.9 [25.8] μm) and PTT increase (1.7 [13.3], 2.4 [11.9], 17.4 [13.7], and 13.9 [18.6] μm). LD was greater in ONHs with larger BMO area (P = 0.01) and deeper ALS (P = 0.04); however, PTT was not associated with any of the tested independent variables., Conclusions: Both anterior LD and thickening of prelaminar tissue occur after surgical IOP reduction in patients with glaucoma.

Objective: To examine peripapillary choroidal thickness in healthy controls and in patients with glaucoma who have focal, diffuse, and sclerotic optic disc damage., Methods: Healthy controls (n=92) and patients with glaucoma who have focal (n=34), diffuse (n=35), and sclerotic (n=34) optic disc damage were imaged with spectral-domain optical coherence tomography (12° circular scan protocol centered on optic nerve head). Peripapillary choroidal thickness was measured as the distance between the automatically segmented retinal pigment epithelium/Bruch's membrane and the manually outlined interface between the posterior choroid and the anterior border of the sclera in eyes in which the anterior scleral border was visible over more than 85% of the scan circumference., Results: The anterior scleral border was visible in 76 controls (83%) and 89 patients (86%). Peripapillary choroidal thickness in healthy controls decreased linearly with age (-11 μm/decade; P.001; r2=0.16), with a predicted value of 137 μm at age 70 years (95% prediction interval, 62-212 μm). While this value was similar in patients with focal and diffuse optic disc damage (126 and 130 μm, respectively; P=.22 compared with controls), it was approximately 30% lower in patients with sclerotic optic disc damage (96 μm; P.001 compared with controls)., Conclusions: The peripapillary choroid of patients with glaucoma who have sclerotic optic disc damage was approximately 25% to 30% thinner compared with that in patients with focal and diffuse optic disc damage and with that in healthy controls. The role of the choroid in the pathophysiology of sclerotic glaucomatous optic disc damage needs further investigation.

Purpose: There is no gold-standard measurement of glaucomatous structural progression against which to validate software progression algorithms. A computer model was developed and validated to simulate stable series of Heidelberg Retina Tomograph II (HRT; Heidelberg Engineering, Heidelberg, Germany) images, with realistic topographic variability, suitable for benchmarking false-positive rates of progression algorithms., Methods: Three confocal image stacks were selected from each of five sets of HRT II scans, obtained within 6 weeks in 127 eyes of 66 patients. For each eye, a simulated series was propagated from one baseline confocal stack by adding fixational eye movements, photon-counting, and electronic measurement noise. Simulated confocal stacks were imported into the HRT software to generate topography images. Real and simulated image comparisons were quantified with the mean pixel height standard deviation (MPHSD), image cross-correlation (CC) of pixel-wise variability maps, and the rim area (RA) coefficient of variation (CV)., Results: The mean difference (95% limits of agreement; LoA) in MPHSD between real and simulated images was 3.5 μm (-20.9 to 28.8 μm) within mean topographies and 2.0 μm (-5.4 to 9.3 μm) between mean topographies. The mean CC between real and simulated spatial variability maps was 0.58 within mean topographies and 0.54 between mean topographies. The mean difference (95% LoA) between real and simulated mean topography RA CV was -2.1% (-17.6% to +13.4%). Variability about anatomic features was well reproduced., Conclusions: Simulation realistically reproduces variability in real, stable images acquired over a short period. Stability in clinical datasets is uncertain, whereas in these modeled series, it is certain. This method provides benchmark datasets on which the specificity of progression algorithms can be tested.

Objective: To compare optic disc changes using automated analysis of Heidelberg retina tomograph (HRT) images with assessments, by glaucoma specialists, of change in stereoscopic photographs., Methods: Baseline and follow-up stereophotographs and corresponding HRT I series of 91 eyes from 56 patients were selected. The selection criteria were sufficiently long, good-quality HRT series (7 visits in > or =70 months of follow-up) and follow-up photographs contemporaneous with the final HRT image. Topographic change analysis (TCA), statistic image mapping (SIM), and linear regression of rim area (RALR) across time were applied to HRT series. Glaucomatous change determined from stereophotographs by expert observers was used as the reference standard., Results: Expert observers identified 33 eyes (36%) as exhibiting glaucomatous change. Altering HRT progression criteria such that 36% of eyes progressed according to each method resulted in concordance between HRT methods and stereophotograph assessment of 54% for TCA, 65% for SIM, and 67% for RALR (Cohen kappa = 0.05, 0.23, and 0.30, respectively). Receiver operating characteristic curves of the HRT analyses revealed poor precision of HRT analyses to predict stereophotograph-assessed change: areas under the curve were 0.61 for TCA, 0.62 for SIM, and 0.66 for RALR., Conclusions: Statistical methods for detecting structural changes in HRT images exhibit only moderate agreement with each other and have poor agreement with expert-assessed change in optic disc stereophotographs.

Purpose: To evaluate the new proper orthogonal decomposition (POD) framework for detecting glaucomatous progression from HRT topographies of human subjects and compare it with HRT topographic change analysis (TCA)., Methods: Of 267 eyes of 187 participants with > or =4 retinal tomographic examinations in the University of California, San Diego Diagnostic Innovations in Glaucoma Study (DIGS), 21 eyes were of longitudinally normal subjects and 36 eyes progressed by stereophotographs or visual field-guided progression analysis (progressors). All others were considered nonprogressing (nonprogressors; n = 210 eyes). POD parameters of Euclidean distance (L(2) norm), image Euclidean distance, and correlation were computed, and their area under receiver operating characteristic curves (AUC) in differentiating progressors from nonprogressors and normal subjects were compared to the TCA parameters of the number of superpixels with significant decrease in retinal height (red pixels), size of the largest cluster of red pixels (CSIZE), and CSIZE% of disc size, all within the optic disc margin., Results: AUCs of the best performing POD L(2) norm and TCA red pixel parameters in differentiating progressors from normal subjects were both 0.86 and in differentiating progressors from nonprogressors were 0.68 and 0.64, respectively; the AUC differences were not statistically significant., Conclusions: The POD framework, which can detect and confirm glaucomatous changes in a single follow-up visit, provides a performance similar to that of TCA in differentiating progressors from normal subjects and nonprogressors.

Purpose: To determine the sensitivity and specificity of confocal scanning laser ophthalmoscope's Topographic Change Analysis (TCA; Heidelberg Retina Tomograph [HRT]; Heidelberg Engineering, Heidelberg, Germany) parameters for discriminating between progressing glaucomatous and stable healthy eyes., Methods: The 0.90, 0.95, and 0.99 specificity cutoffs for various (n=70) TCA parameters were developed by using 1000 permuted topographic series derived from HRT images of 18 healthy eyes from Moorfields Eye Hospital, imaged at least four times. The cutoffs were then applied to topographic series from 36 eyes with known glaucomatous progression (by optic disc stereophotograph assessment and/or standard automated perimetry guided progression analysis, [GPA]) and 21 healthy eyes from the University of California, San Diego (UCSD) Diagnostic Innovations in Glaucoma Study (DIGS), all imaged at least four times, to determine TCA sensitivity and specificity. Cutoffs also were applied to 210 DIGS patients' eyes imaged at least four times with no evidence of progression (nonprogressed) by stereophotography or GPA., Results: The TCA parameter providing the best sensitivity/specificity tradeoff using the 0.90, 0.95, and 0.99 cutoffs was the largest clustered superpixel area within the optic disc margin (CAREA(disc) mm(2)). Sensitivities/specificities for classifying progressing (by stereophotography and/or GPA) and healthy eyes were 0.778/0.809, 0.639/0.857, and 0.611/1.00, respectively. In nonprogressing eyes, specificities were 0.464, 0.570, and 0.647 (i.e., lower than in the healthy eyes). In addition, TCA parameter measurements of nonprogressing eyes were similar to those of progressing eyes., Conclusions: TCA parameters can discriminate between progressing and longitudinally observed healthy eyes. Low specificity in apparently nonprogressing patients' eyes suggests early progression detection using TCA.

Purpose: To examine whether patients with glaucoma exhibit differences in visually guided reaching-and-grasping (prehension) behavior compared with normally sighted control subjects., Methods: Sixteen patients with glaucoma and 16 control subjects with no ocular disease participated. Participants were required to reach out and precision grasp one of two cylindrical objects placed on a table top in front of them in laboratory conditions in three viewing conditions (binocular, right eye alone, left eye alone). Lightweight reflective markers were placed on the subject's preferred hand for recording its movement in three-dimensional space. Three motion capture units recorded the motion of these markers as the subjects reached out and precision grasped household objects. Various indices of prehension planning, execution, and control were quantified. Visual fields (VF) were measured using standard automated perimetry generating monocular mean deviation (MD) scores. Binocular VF sensitivity was estimated by using the integrated visual field (IVF). Stereoacuity was measured with the Frisby stereoacuity test. Significant differences in prehension movement between patients and control subjects in each viewing condition were investigated, and associations between prehension kinematics and VF sensitivity were examined., Results: The patients and control subjects were of a similar age (median [range]: patient group, 72.2 years [62.5-86.9]; control group, 69.0 years [64.3-78.3]). The patient group had asymmetrical disease and relatively minor binocular overlapping defects (better eye MD, -5.7 dB [-16.7 to +0.45 dB]; worse eye MD, -11.8 dB [-29.3 to -1.5 dB]; IVF score, 3 [0-36]). They exhibited slightly poorer stereoacuity levels than did the control subjects (patient group, 55 sec arc [40-110]; control group, 40 sec arc [20-80; Mann-Whitney U test, P < 0.05]). They also showed statistically significant delays in average movement onset (MO: approximately 100 ms delay, Mann-Whitney U test P < 0.0001) and overall movement time (OMD: approximately 140 ms delay; Mann-Whitney U test P < 0.05), suggesting impairments in initial movement planning and control. Deficits were exhibited in the reaching component, with data suggesting that glaucomatous patients made more tentative movements when reaching for the object. These deficits correlated with both increasing severity of VF defect and impaired stereoacuity. There were no differences in grasping characteristics between patients and control subjects in this sample., Conclusions: This study provides evidence that patients with glaucoma exhibit deficits in eye-hand coordination compared with the age-matched normally sighted control. Further study is needed to assess the specific effect of field loss location on prehension kinematics.