Progressive Changes in the Neuroretinal Rim and Retinal Nerve Fiber Layer in Glaucoma: Impact of Baseline Values and Floor Effects.

PURPOSE: To determine whether more severe baseline damage impedes measurement of minimum rim width (MRW) and peripapillary retinal nerve fiber layer thickness (RNFLT) change in glaucoma patients because of a floor effect. DESIGN: Prospective, longitudinal cohort study in a hospital-based setting. PARTICIPANTS: The study included patients with open-angle glaucoma and healthy control subjects. Participants had at least 5 years of follow-up with OCT every 6 months. METHODS: Baseline global and sectorial MRW and RNFLT values were classified as within normal limits, borderline, or outside normal limits based on reference normative values. Regression analysis was used to determine the magnitude and significance of MRW and RNFLT change. Additionally, the follow-up period for each participant was divided into 2 equal halves (first and second periods) to determine whether there was attenuation of MRW and RNFLT change with follow-up time. MAIN OUTCOME MEASURES: Rates of global and sectoral MRW and RNFLT changes (slopes). RESULTS: A total of 97 patients with glaucoma (median age, 70.3 years) and 42 healthy subjects (median age, 64.8 years) were followed for a median of 6.9 years and 7.0 years, respectively. The median mean deviation of the visual field in glaucoma patients was -4.30 decibels (dB) (interquartile range, -7.81 to -2.06 dB; range, -20.68 to 1.37 dB). Statistically significant changes in global and sectoral MRW and RNFLT were detected across all baseline classifications; however, there was a tendency for less change with increasing baseline damage. In glaucoma patients, RNFLT slopes, but not MRW slopes, were significantly more positive (less change) in the second period compared with the first. There were also no differences in MRW or RNFLT slopes in the first and second periods in healthy subjects. CONCLUSIONS: Significant MRW and RNFLT changes were detected at all levels of baseline damage. However, an attenuation in the rate of RNFLT change compared with MRW indicates an earlier floor effect in RNFLT measurements globally and in equivalent sectors. Because the axonal component of these measurements should be equivalent, our results suggest important differences in tissue remodeling at the level of the optic nerve head and peripapillary retina. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Value of 10-2 Visual Field Testing in Glaucoma Patients with Early 24-2 Visual Field Loss.

PURPOSE: To determine whether the 10-2 test of the Humphrey Field Analyzer detected a higher proportion of abnormal visual fields compared with the 24-2 test in the central 10° of patients with early glaucomatous visual field damage. DESIGN: Prospective observational study. PARTICIPANTS: Patients with open-angle glaucoma and healthy control participants. METHODS: All participants underwent a 24-2 and 10-2 test. Only the 12 central test locations of the 24-2 test were included to analyze equivalent visual field areas. The performance of the 2 tests was compared across 4 pointwise criteria: total deviation (TD) and pattern deviation (PD) analyses at the 5% and 2% levels. Analyses also were conducted for 2 pairs of follow-up tests, each performed 4 months apart. MAIN OUTCOME MEASURES: (1) Area under the receiver operating characteristic curve (AUC), (2) sensitivity at identically matched specificity for the 4 criteria, (3) overlap (entire field and by quadrant) of abnormal visual fields with both tests, and (4) repeatability of the findings in 2 subsequent follow-up tests. RESULTS: One eye each of 97 glaucoma patients (median mean deviation, -2.31 dB) and 65 control participants were included in the study. The AUCs for the 24-2 and 10-2 tests were not significantly different for any of the 4 criteria and ranged from 0.88 to 0.93 and from 0.91 to 0.94, respectively. At matched specificity, the sensitivity of the 24-2 test was significantly higher for all criteria except for PD analysis at 5%. In patients with an abnormal field with either test, the overlap varied from 60% to 86% depending on the criterion, whereas by quadrant, concordance ranged from 70% to 87%. Over the follow-up, the repeatability of test results (both 24-2 and 10-2 abnormal, either abnormal, or both normal) was achieved in 55% to 70% of patients. CONCLUSIONS: In this study of glaucoma patients with early damage with the 24-2 test, there was little evidence that adding the 10-2 test revealed additional undetected defects in the central visual field. It may be more prudent to reserve 10-2 testing for following up selected patients with higher risk of central visual field progression.

Differential Effects of Aging in the Macular Retinal Layers, Neuroretinal Rim, and Peripapillary Retinal Nerve Fiber Layer.

PURPOSE: We determined the differential aging effects of the inner 6 layers of the macula in contrast to the minimum neuroretinal rim width (MRW) and peripapillary retinal nerve fiber layer (RNFL) thickness. DESIGN: Cross-sectional, multicenter study. PARTICIPANTS: An approximately equal number of white subjects with a normal ocular and visual field examination in each decade group from 20 to 90 years. METHODS: OCT of the macula, optic nerve head, and peripapillary retina. MAIN OUTCOME MEASURES: Sectoral measurements of the inner 6 layers of the macula; age-related decline of each of these layers; strength of the associations with age of the macular parameters, MRW, and peripapillary RNFL thickness; and association between ganglion cell layer (GCL) thickness and MRW and peripapillary RNFL thickness. RESULTS: The study sample comprised 1 eye of 246 subjects with a median (range) age of 52.9 (19.8-87.3) years. Of the 6 layers, there was a statistically significant decline with age of only the GCL, inner plexiform layer, and inner nuclear layer thickness with rates of -0.11 µm/year, -0.07 µm/year, and -0.03 µm/year, respectively. These rates corresponded to 2.82%, 2.10%, and 0.78% loss per decade, respectively, and were generally uniform across sectors. The rate of loss of MRW and peripapillary RNFL thickness was -1.22 µm/year and -0.20 µm/year, corresponding to 3.75% and 2.03% loss per decade. However, the association of GCL thickness change with age (R2 = 0.28) was approximately twice that of MRW and RNFL thickness (R2 = 0.14 for each). CONCLUSIONS: In concordance with histopathologic studies showing age-related loss of retinal ganglion cell axons, we showed a significant decline in GCL thickness, as well as MRW and peripapillary RNFL thickness. The stronger relationship between aging and GCL thickness compared with the rim or peripapillary RNFL may indicate that GCL thickness could be better suited to measure progression of structural glaucomatous loss.

Serial Changes in Lamina Cribrosa Depth and Neuroretinal Parameters in Glaucoma: Impact of Choroidal Thickness.

PURPOSE: To determine whether: (1) change in lamina cribrosa depth occurs more frequently than change in neuroretinal parameters in glaucoma, and (2) Bruch's membrane or anterior sclera should be used as a reference plane when measuring laminar depth. DESIGN: Prospective observational study. PARTICIPANTS: One hundred fifty-five glaucoma patients and 35 healthy controls. METHODS: Anterior laminar depth from a Bruch's membrane (LD-BM) or anterior sclera (LD-AS) reference plane were measured with optical coherence tomography. Two neuroretinal parameters, minimum rim width and retinal nerve fiber layer thickness, in addition to peripapillary choroidal thickness were measured. Factors related to laminar depth were determined with mixed-effects modeling. Cutoffs for significant change in each parameter were estimated from variability in healthy controls over 1 year. The occurrences of significant change in laminar depth and neuroretinal parameters were compared with survival models. Because normal aging has a clear effect on neuroretinal parameters, but not on laminar depth, changes in neuroretinal parameters were adjusted for age-related reduction. MAIN OUTCOME MEASURES: Longitudinal changes in laminar depth and neuroretinal parameters. RESULTS: Glaucoma patients were followed up for a mean of 3.90 years (range, 2.03-5.44 years). The LD-BM was influenced significantly more by choroidal thickness (1.14 µm/µm; 95% confidence interval, 1.07-1.21) than was the LD-AS (0.15 µm/µm; 95% confidence interval, 0.08-0.22). Posterior movement of the lamina (LD-BM increase or LD-AS increase) occurred with the same frequencies as thinning in neuroretinal parameters. Anterior movement of the lamina was detected more frequently with the Bruch's membrane (LD-BM decrease) compared with the anterior sclera (LD-AS decrease) reference plane (hazard ratio, 3.23; P < 0.01). Significant choroidal thinning occurred in most patients (25/28 [89%]) in whom anterior movement of the lamina occurred with the Bruch's membrane, but not the anterior sclera, reference plane (LD-BM decrease without LD-AS decrease). Patients had a wide range of individual rates of change of choroidal thickness, from -20.00 to 17.09 µm/year (mean, -1.62 µm/year). CONCLUSIONS: Lamina cribrosa depth should be measured from an anterior sclera reference plane to reduce the influence of choroidal thickness changes. In glaucoma patients, lamina cribrosa depth changes are detected with similar frequency as neuroretinal parameter changes.

Diagnostic Accuracy of Optical Coherence Tomography and Scanning Laser Tomography for Identifying Glaucoma in Myopic Eyes.

PURPOSE: Ruling out glaucoma in myopic eyes often poses a diagnostic challenge because of atypical optic disc morphology and visual field defects that can mimic glaucoma. We determined whether neuroretinal rim assessment based on Bruch's membrane opening (BMO), rather than conventional optic disc margin (DM)-based assessment or retinal nerve fiber layer (RNFL) thickness, yielded higher diagnostic accuracy in myopic patients with glaucoma. DESIGN: Case-control, cross-sectional study. PARTICIPANTS: Myopic patients with glaucoma (n = 56) and myopic normal controls (n = 74). METHODS: Myopic subjects with refraction error greater than -2 diopters (D) (spherical equivalent) and typical myopic optic disc morphology, with and without glaucoma, were recruited from a glaucoma clinic and a local optometry practice. The final classification of myopic glaucoma or myopic control was based on consensus assessment by 3 clinicians of visual fields and optic disc photographs. Participants underwent imaging with confocal scanning laser tomography for measurement of DM rim area (DM-RA) and with spectral domain optical coherence tomography (SD OCT) for quantification of a BMO-based neuroretinal rim parameter, minimum rim width (BMO-MRW), and RNFL thickness. MAIN OUTCOME MEASURES: Sensitivity of DM-RA, BMO-MRW, and RNFL thickness at a fixed specificity of 90% and partial area under the curves (pAUCs) for global and sectoral parameters for specificities ≥90%. RESULTS: Sensitivities at 90% specificity were 30% for DM-RA and 71% for both BMO-MRW and RNFL thickness. The pAUC was higher for the BMO-MRW compared with DM-RA (P < 0.001), but similar to RNFL thickness (P > 0.5). Sectoral values of BMO-MRW tended to have a higher, but nonsignificant, pAUC across all sectors compared with RNFL thickness. CONCLUSIONS: Bruch's membrane opening MRW is more sensitive than DM-RA and similar to RNFL thickness for the identification of glaucoma in myopic eyes and offers a valuable diagnostic tool for patients with glaucoma with myopic optic discs.

Optic Disc Hemorrhages and Laminar Disinsertions in Glaucoma.

PURPOSE: To determine whether structural abnormalities of the lamina cribrosa explain the presence of optic disc hemorrhages, we determined the spatial concordance between disc hemorrhages and laminar disinsertions from the sclera. DESIGN: Prospective noninterventional study. PARTICIPANTS: From open-angle glaucoma patients followed up prospectively, we identified 52 eyes of 46 open-angle glaucoma patients with optic disc hemorrhage (ODH+ group) in at least 1 optic disc photograph during follow-up. We also identified 52 control eyes of 46 glaucoma patients in whom no disc hemorrhage was detected (ODH- group). METHODS: Enhanced depth imaging optical coherence tomography of the optic nerve head (24 radial scans) was performed. The scans were de-identified and a trained observer masked to all clinical information determined the presence of laminar disinsertions in each of the 48 positions with a confidence score of 1 (least certain) to 5 (most certain). Only disinsertions with a score of 3 or more were included in the analysis. MAIN OUTCOME MEASURES: Frequency and spatial concordance between disc hemorrhages and laminar disinsertions. RESULTS: The median age, visual field mean deviation, and follow-up period of the ODH+ and ODH- groups was 77.5 and 70.8 years, -5.20 and -4.70 dB, and 10.4 and 9.9 years, respectively. There were 84 hemorrhages recorded in the ODH+ group. There were laminar disinsertions in 50 eyes (96%) in the ODH+ group and in 27 eyes (52%) in the ODH- group, with 2 or more disinsertions in 30 eyes (58%) and 5 eyes (10%), respectively. Most hemorrhages and disinsertions were located in the inferotemporal and superotemporal sectors. However, in individual patients, only 33 of the ODHs (39%) were located within a laminar disinsertion. CONCLUSIONS: Laminar disinsertions occurred twice as frequently in eyes with ODHs; however, in individual patients, the spatial concordance between ODHs and laminar disinsertions was poor.

Importance of Normal Aging in Estimating the Rate of Glaucomatous Neuroretinal Rim and Retinal Nerve Fiber Layer Loss.

PURPOSE: To describe longitudinal rates of change of neuroretinal parameters in patients with glaucoma and healthy controls, and to evaluate the influence of covariates. DESIGN: Prospective longitudinal study. PARTICIPANTS: Treated patients with glaucoma (n = 192) and healthy controls (n = 37). METHODS: Global disc margin-based neuroretinal rim area (DMRA) was measured with confocal scanning laser tomography, while Bruch's membrane opening-minimum rim width (BMO-MRW), BMO area (BMOA), and peripapillary retinal nerve fiber layer thickness (RNFLT) were measured with optical coherence tomography at 6-month intervals. Individual rates of change were estimated with ordinary least-squares regression, and linear mixed effects modeling was used to estimate the average rate of change and differences between the groups, and to evaluate the effects of baseline measurement and baseline age on rates of change. MAIN OUTCOME MEASURES: Rates of change for each parameter. RESULTS: Subjects were followed for a median (range) of 4 (2-6) years. The proportion of controls who had significant reduction of neuroretinal parameters was 35% for BMO-MRW, 31% for RNFLT, and 11% for DMRA. The corresponding figures for patients with glaucoma were not statistically different (42%, P = 0.45; 31%, P = 0.99; 14%, P = 0.99, respectively). Controls had a significant reduction of BMO-MRW (mean: -1.92 µm/year, P < 0.01) and RNFLT (mean: -0.44 µm/year, P = 0.01), but not DMRA (mean: -0.22×10(-2) mm(2)/year, P = 0.41). After adjusting for covariates, patients with glaucoma had faster, but not statistically different, rates of deterioration compared with controls, by -1.26 µm/year (P = 0.07) for BMO-MRW, -0.40 µm/year (P = 0.11) for RNFLT, and -0.38×10(-2) mm(2)/year (P = 0.23) for DMRA. Baseline BMO-MRW and RNFLT significantly influenced the respective rates of change, with higher baseline values relating to faster reductions. Older age at baseline was associated with a slower reduction in rates of BMO-MRW. Reductions in intraocular pressure were related to increases in BMO-MRW and DMRA. There was a tendency for BMOA to decrease over time (-0.38×10(-2) mm(2)/year; P = 0.04). CONCLUSIONS: Age-related loss of neuroretinal parameters may explain a large proportion of the deterioration observed in treated patients with glaucoma and should be carefully considered in estimating rates of change.

Bruch's Membrane Opening Minimum Rim Width and Retinal Nerve Fiber Layer Thickness in a Normal White Population: A Multicenter Study.

PURPOSE: Conventional optic disc margin-based neuroretinal rim measurements lack a solid anatomic and geometrical basis. An optical coherence tomography (OCT) index, Bruch's membrane opening minimum rim width (BMO-MRW), addresses these deficiencies and has higher diagnostic accuracy for glaucoma. We characterized BMO-MRW and peripapillary retinal nerve fiber layer thickness (RNFLT) in a normal population. DESIGN: Multicenter cross-sectional study. PARTICIPANTS: Normal white subjects. METHODS: An approximately equal number of subjects in each decade group (20-90 years of age) was enrolled in 5 centers. Subjects had normal ocular and visual field examination results. We obtained OCT images of the optic nerve head (24 radial scans) and peripapillary retina (1 circular scan). The angle between the fovea and BMO center (FoBMO angle), relative to the horizontal axis of the image frame, was first determined and all scans were acquired and analyzed relative to this eye-specific FoBMO axis. Variation in BMO-MRW and RNFLT was analyzed with respect to age, sector, and BMO shape. MAIN OUTCOME MEASURES: Age-related decline and between-subject variability in BMO-MRW and RNFLT. RESULTS: There were 246 eyes of 246 subjects with a median age of 52.9 years (range, 19.8-87.3 years). The median FoBMO angle was -6.7° (range, 2.5° to -17.5°). The BMO was predominantly vertically oval with a median area of 1.74 mm(2) (range, 1.05-3.40 mm(2)). Neither FoBMO angle nor BMO area was associated with age or axial length. Both global mean BMO-MRW and RNFLT declined with age at a rate of -1.34 µm/year and -0.21 µm/year, equivalent to 4.0% and 2.1% loss per decade of life, respectively. Sectorially, the most rapid decrease occurred inferiorly and the least temporally; however, the age association was always stronger with BMO-MRW than with RNFLT. There was a modest relationship between mean global BMO-MRW and RNFLT (r = 0.35), whereas sectorially the relationship ranged from moderate (r = 0.45, inferotemporal) to nonexistent (r = 0.01, temporal). CONCLUSIONS: There was significant age-related loss of BMO-MRW in healthy subjects and notable differences between BMO-MRW and RNFLT in their relationship with age and between each other. Adjusting BMO-MRW and RNFLT for age and sector is important in ensuring optimal diagnostics for glaucoma.

Optical Coherence Tomographic Optic Nerve Head Morphology in Myopia III: The Exposed Neural Canal Region in Healthy Eyes-Implications for High Myopia.

PURPOSE: To determine the prevalence and magnitude of optical coherence tomography (OCT) exposed neural canal (ENC), externally oblique choroidal border tissue (EOCBT), and exposed scleral flange (ESF) regions in 362 non-highly myopic (spherical equivalent -6.00 to 5.75 diopters) eyes of 362 healthy subjects. DESIGN: Cross-sectional study. METHODS: After OCT optic nerve head (ONH) imaging, Bruch membrane opening (BMO), the anterior scleral canal opening (ASCO), and the scleral flange opening (SFO) were manually segmented. BMO, ASCO, and SFO points were projected to the BMO reference plane. The direction and magnitude of BMO/ASCO offset as well as the magnitude of ENC, EOCBT, and ESF was calculated within 30° sectors relative to the foveal-BMO axis. Hi-ESF eyes demonstrated an ESF ≥100 µm in at least 1 sector. Sectoral peri-neural canal choroidal thickness (pNC-CT) was measured and correlations between the magnitude of sectoral ESF and proportional pNC-CT were assessed. RESULTS: Seventy-three Hi-ESF (20.2%) and 289 non-Hi-ESF eyes (79.8%) were identified. BMO/ASCO offset as well as ENC, EOCBT, and ESF prevalence and magnitude were greatest inferior temporally where the pNC-CT was thinnest. Among Hi-ESF eyes, the magnitude of each ENC region correlated with the BMO/ASCO offset magnitude, and the sectors with the longest ESF correlated with the sectors with proportionally thinnest pNC-CT. CONCLUSIONS: ONH BMO/ASCO offset, either as a cause or result of ONH neural canal remodeling, corresponds with the sectoral location of maximum ESF and minimum pNC-CT in non-highly myopic eyes. Longitudinal studies to characterize the development and clinical implications of ENC Hi-ESF regions in non-highly myopic and highly myopic eyes are indicated.

Enhanced detection of open-angle glaucoma with an anatomically accurate optical coherence tomography-derived neuroretinal rim parameter.

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.

Analysis of deep optic nerve head structures with spectral domain and swept-source optical coherence tomography.

PURPOSE: Histological evidence indicates that the earliest structural changes to the optic nerve head (ONH) in glaucoma occur in the lamina cribrosa (LC) and its interface with the sclera. However, clinical imaging of these structures remains challenging. We compared the visibility of deep ONH structures with newer iterations of spectral-domain (SD) and swept-source (SS) optical coherence tomography (OCT). METHODS: Twelve patients with open-angle glaucoma were imaged with SD-OCT with 24 radial B-scans centred on Bruch's membrane opening (BMO) and SS-OCT with a horizontal and vertical raster scan pattern containing five lines each, centred on the ONH. Single best-matched horizontal and vertical scans from the two modalities were selected and exported. Three independent observers masked to modality determined if BMO, posterior choroid surface, anterior scleral canal opening and anterior and posterior LC insertions into the sclera were detectable in the matched B-scan images. We determined the interobserver agreement and concordance in detecting each structure with the two OCT imaging modalities. RESULTS: There was a high interobserver agreement with both SS-OCT and SD-OCT (inter-item correlations: 0.81-0.93 and 0.77-0.82, respectively). There was a consistent tendency for higher overall detection rates with SS-OCT, however, the differences failed to reach statistical significance. With respect to individual structures, only the posterior LC insertion in the nasal quadrant was statistically different, with a detection rate of 13 and 6 (pooled out of a total of 36 across the three observers) with SS-OCT and SD-OCT, respectively (p=0.04). CONCLUSION: Overall, both SS-OCT and SD-OCT showed statistically equivalent visualisation of ONH structures, however, SS-OCT tended to have higher visualisation rates.

Variability of scan quality and perfusion density in longitudinal optical coherence tomography angiography imaging.

BACKGROUND/AIMS: Optical coherence tomography angiography (OCT-A) images are subject to variability, but the extent to which learning impacts OCT-A measurements is unknown. We determined whether there is a learning effect in glaucoma patients and healthy controls imaged with OCT-A. METHODS: Ninety-one open-angle glaucoma patients and 54 healthy controls were imaged every 4 months over a period of approximately 1 year in this longitudinal cohort study. We analysed 15°×15° scans, centred on the fovea, in one eye of each participant. Two-dimensional projection images for the superficial, intermediate and deep vascular plexuses were exported and binarised after which perfusion density was calculated. Linear mixed-effects models were used to investigate the association between perfusion density and follow-up time. RESULTS: The mean (SD) age of glaucoma patients and healthy controls was 67.3 (8.1) years and 62.1 (9.0) years, respectively. There was a significant correlation between perfusion density and scan quality in both glaucoma patients (r=0.50 (95% CI 0.42 to 0.58); p<0.05) and healthy controls (r=0.41 (95% CI 0.29 to 0.52); p<0.05). An increase in perfusion density occurred over time and persisted, even after adjustment for scan quality (1.75% per year (95% CI 1.14 to 2.37), p<0.01). CONCLUSIONS: Perfusion density measurements are subject to increasing experience of either the operator or participant, or a combination of both. These findings have implications for the interpretation of longitudinal measurements with OCT-A.

Asymmetry of Peripapillary Retinal Blood Vessel and Retinal Nerve Fiber Layer Thickness Between Healthy Right and Left Eyes.

Purpose: The purpose of this study was to determine if there is asymmetry in retinal blood vessel (RBV) position and thickness between right and left eyes (R-L) and evaluate whether R-L asymmetry in RBV thickness is related to R-L asymmetry of retinal nerve fiber layer thickness (RNFLT). Methods: We analyzed peripapillary circle scan optical coherence tomography (OCT) examinations from healthy White subjects to measure RNFLT and RBV thickness and position relative to the fovea to Bruch's membrane opening axis, for all visible RBV. The R-L asymmetries of RNFLT and RBV thickness were computed for each A-scan. Four major vessels (superior temporal artery [STA] and superior temporal vein [STV], inferior temporal artery [ITA], and vein [ITV]) were identified using infrared images. Results: We included 219 individuals. The mean (standard deviation) number of RBV measured per eye was 15.0 (SD = 2.2). The position of the STV and STA was more superior in left eyes than in right eyes, by 2.4 degrees and 3.7 degrees, respectively (P < 0.01). There was no region with significant R-L asymmetry in RBV thickness. RNFLT was thicker in right eyes in the temporal superior region and thicker in left eyes in the superior and nasal superior regions, with the asymmetry profile resembling in a "W" shape. This shape was also present in post hoc analyses in two different populations. The R-L asymmetries of RBV and RNFLT at each A-scan were not significantly associated (P = 0.37). Conclusions: There is little R-L asymmetry in RBV, and it is not related to RNFLT asymmetry. This study suggests that R-L RNFLT asymmetry is due to factors other than RBV.

Optic disc margin anatomy in patients with glaucoma and normal controls with spectral domain optical coherence tomography.

OBJECTIVE: To characterize optic nerve head (ONH) anatomy related to the clinical optic disc margin with spectral domain-optical coherence tomography (SD-OCT). DESIGN: Cross-sectional study. PARTICIPANTS: Patients with open-angle glaucoma with focal, diffuse, and sclerotic optic disc damage, and age-matched normal controls. METHODS: High-resolution radial SD-OCT B-scans centered on the ONH were analyzed at each clock hour. For each scan, the border tissue of Elschnig was classified for obliqueness (internally oblique, externally oblique, or nonoblique) and the presence of Bruch's membrane overhanging the border tissue. Optic disc stereophotographs were co-localized to SD-OCT data with customized software. The frequency with which the disc margin identified in stereophotographs coincided with (1) Bruch's membrane opening (BMO), defined as the innermost edge of Bruch's membrane; (2) Bruch's membrane/border tissue, defined as any aspect of either outside BMO or border tissue; or (3) border tissue, defined as any aspect of border tissue alone, in the B-scans was computed at each clock hour. MAIN OUTCOME MEASURES: The SD-OCT structures coinciding with the disc margin in stereophotographs. RESULTS: There were 30 patients (10 with each type of disc damage) and 10 controls, with a median (range) age of 68.1 (42-86) years and 63.5 (42-77) years, respectively. Although 28 patients (93%) had 2 or more border tissue configurations, the most predominant one was internally oblique, primarily superiorly and nasally, frequently with Bruch's membrane overhang. Externally oblique border tissue was less frequent, observed mostly inferiorly and temporally. In controls, there was predominantly internally oblique configuration around the disc. Although the configurations were not statistically different between patients and controls, they were among the 3 glaucoma groups. At most locations, the SD-OCT structure most frequently identified as the disc margin was some aspect of Bruch's membrane and border tissue external to BMO. Bruch's membrane overhang was regionally present in the majority of patients with glaucoma and controls; however, in most cases it was not visible as the disc margin. CONCLUSIONS: The clinically perceived disc margin is most likely not the innermost edge of Bruch's membrane detected by SD-OCT. These findings have important implications for the automated detection of the disc margin and estimates of the neuroretinal rim.

Elucidating macular structure-function correlations in glaucoma.

Correlation between structural data from optical coherence tomography and functional data from the visual field may be suboptimal because of poor mapping of OCT measurement locations to VF stimuli. We tested the hypothesis that stronger structure-function correlations in the macula can be achieved with fundus-tracking perimetery, by precisely mapping OCT measurements to VF sensitivity at the same location. The conventional 64 superpixel (3° × 3°) OCT grid was mapped to VF sensitivities averaged in 40 corresponding VF units with standard automated perimetry (conventional mapped approach, CMA) in 38 glaucoma patients and 10 healthy subjects. Similarly, a 144 superpixel (2° × 2°) OCT grid was mapped to each of the 68 locations with fundus-tracking perimetry (localized mapped approach, LMA). For each approach, the correlation between sensitivity at each VF unit and OCT superpixel was computed. Vector maps showing the maximum correlation between each VF unit and OCT pixel was generated. CMA yielded significantly higher structure-function correlations compared to LMA. Only 20% of the vectors with CMA and < 5% with LMA were within corresponding mapped OCT superpixels, while most were directed towards loci with structural damage. Measurement variability and patterns of structural damage more likely impact correlations compared to precise mapping of VF stimuli.

Impact of Glaucoma Severity on Rates of Neuroretinal Rim, Retinal Nerve Fiber Layer, and Macular Ganglion Cell Layer Thickness Change.

PURPOSE: To determine the impact of glaucoma severity on rates of change of minimum rim width (MRW), peripapillary retinal nerve fiber layer (RNFL), and macular ganglion cell layer (GCL) thickness. DESIGN: Prospective, cohort study. METHODS: Glaucoma patients and healthy subjects had optical coherence tomography scans at 6-month intervals. Individual rates of change for MRW, RNFL, and GCL thickness were estimated with ordinary least-squares regression. Linear mixed-effect models were used to estimate the rate of change of each parameter and evaluate the impact of glaucoma severity (expressed by visual field mean deviation, MD) and age on these rates. RESULTS: A total of 132 glaucoma patients and 57 healthy subjects were followed for a median of 4.3 years and 3.7 years, respectively. Healthy subjects had a statistically significant deterioration in MRW (-1.66 µm/year), RNFL (-0.46 µm/year), and GCL thickness (-0.22 µm/year). While glaucoma patients had a faster rate of change in each parameter compared with healthy subjects, only GCL thickness showed a statistically significant group difference (mean difference: -0.17 µm/year; P = .03). Older baseline age was associated with faster GCL thickness change (-0.07 µm/year; P = .03), but not other parameters. Baseline MD had no impact on the subsequent rates of change in any of the parameters. CONCLUSIONS: The rates of MRW, RNFL, and GCL thickness change were not significantly influenced by glaucoma severity at baseline; however, GCL thickness was able to statistically contrast the rate of change between healthy subjects and glaucoma patients throughout the disease spectrum.

Laminar and prelaminar tissue displacement during intraocular pressure elevation in glaucoma patients and healthy controls.

OBJECTIVE: To determine the response of the anterior lamina cribrosa and prelaminar tissue to acute elevation of intraocular pressure (IOP) in glaucoma patients and healthy subjects. DESIGN: Prospective case-control series. PARTICIPANTS AND CONTROLS: Patients with open-angle glaucoma (n = 12; mean age ± standard deviation [SD], 66.8 ± 6.0 years), age-matched healthy controls (n = 12; mean age ± SD, 67.1 ± 6.2 years), and young controls (n = 12; mean age ± SD, 36.1 ± 11.7 years). METHODS: One eye was imaged with spectral-domain optical coherence tomography to obtain 12 high-resolution radial scans centered on the optic disc. Imaging was repeated at precisely the same locations with an ophthalmodynamometer held perpendicular to the globe via the inferior lid to raise the IOP. A line joining Bruch's membrane opening in 4 radial scans was used as reference in the baseline and elevated IOP images. The vertical distance from the reference line to the anterior prelaminar tissue surface and anterior laminar surface was measured at equidistant points along the reference line in the 2 sets of images. The difference between the 2 sets of corresponding measurements were used to determine laminar displacement (LD) and prelaminar tissue displacement (PTD). MAIN OUTCOME MEASURES: Laminar displacement and PTD. RESULTS: Intraocular pressure elevation among patients, age-matched controls, and young controls was similar (mean ± SD, 12.4 ± 3.2 mmHg). The mean ± SD LD and PTD were 0.5 ± 3.3 µm and 15.7 ± 15.5 µm, respectively. The LD was not statistically different from 0 (P = 0.366), but PTD was (P < 0.001). The mean ± SD LD was similar among the groups (-0.5 ± 3.7 µm, 0.2 ± 2.0 µm, and 2.0 ± 3.6 µm, respectively; P = 0.366), whereas the mean ± SD PTD was different (6.8 ± 13.7 µm, 20.8 ± 17.5 µm, and 19.6 ± 11.8 µm, respectively; P = 0.045). In all subjects, the PTD was greater than LD. In multivariate regression analyses, LD was negatively associated with optic disc size (P = 0.007), whereas PTD was positively associated with the degree of IOP elevation (P = 0.013). CONCLUSIONS: In glaucoma patients and controls, the anterior laminar surface is noncompliant to acute IOP elevation. Acute optic disc surface changes represent compression of prelaminar tissue and not laminar displacement.

Discrepancy in Loss of Macular Perfusion Density and Ganglion Cell Layer Thickness in Early Glaucoma.

PURPOSE: To identify characteristics of patients with early open-angle glaucoma exhibiting greater macular perfusion density (PD) loss compared with macular ganglion cell layer (GCL) thickness loss. DESIGN: Cross-sectional study. METHODS: Optical coherence tomography (OCT) imaging of the optic nerve head and macula was conducted in patients and healthy control subjects. Minimum rim width, retinal nerve fiber layer and GCL thickness, and PD from OCT angiography were derived. Only high-quality images were included. For direct comparison, raw PD and GCL thickness values in patients were converted to relative age-corrected loss values based on data from controls. Demographic and ocular variables related to greater PD loss compared with GCL thickness loss were identified with multivariate logistic regression. RESULTS: Data from 89 patients (median mean deviation with the 24-2 and 10-2 tests, Humphrey Field Analyzer: -1.96 dB and -1.49 dB, respectively) and 54 controls were analyzed. Sixty-three (71%) patients had relatively more GCL thickness loss, whereas 26 (29%) had relatively more PD loss. More PD loss was associated with lower OCT and OCT-angiography signal strength (odds ratio [95% confidence interval], 0.64 [0.40, 0.96] and 0.60 [0.38, 0.86], per dB, respectively), thicker retinal nerve fiber layer thickness (1.08 [1.01, 1.16] per µm), and female sex (6.57 [1.25, 48.79]). CONCLUSION: Less than one-third of patients with early glaucoma had more loss of perfusion compared with conventional structural loss in the macula. Even within a range of high-quality images, lower signal strength may be at least partially responsible for apparent perfusion loss.

Asymmetry analysis of macular optical coherence tomography angiography in patients with glaucoma and healthy subjects.

BACKGROUND/AIMS: Quantitative analysis of optical coherence tomography angiography (OCT-A) images requires a reproducible approach that accounts for sectoral loss. The objective of this study was to determine whether an index that accounts for both global (perfusion density, PD) and asymmetric loss of perfusion, rather than PD alone, more reliably measures loss of perfusion in patients with glaucoma. METHODS: We analysed macular OCT-A scans of 95 glaucoma patients and 59 control subjects. Two-dimensional projection images corresponding to the superficial vascular plexus were exported and analyses performed to calculate global PD and image asymmetry. An unsigned perfusion asymmetry index (PAI) that included PD and asymmetry (with 1:1 wt) was calculated. Perfusion density and PAI were compared with 10-2 visual field mean deviation and ganglion cell layer (GCL) thickness. RESULTS: Median (IQR) visual field mean deviation was -1.73 (-3.76, 0.30) dB for the glaucoma group and 0.67 (0.16, 1.18) dB for the control group. The strength of the correlation with mean deviation was stronger for PAI (r=0.47), compared with PD (r=0.35), whereas with GCL thickness they were comparable (r=0.45 and 0.43, respectively). Compared with controls, mean PD was 12% lower in patients with glaucoma (0.27 vs 0.30), while PAI was 17% lower (0.40 vs 0.48). However, diagnostic accuracy of either PD or PAI was worse than GCL thickness. CONCLUSIONS: While PAI yielded better correlation with mean deviation and GCL thickness, and a slightly improved separation between patients with glaucoma and healthy controls, diagnostic accuracy was inferior compared with GCL thickness.