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.

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.

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.

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.

OCT Optic Nerve Head Morphology in Myopia II: Peri-Neural Canal Scleral Bowing and Choroidal Thickness in High Myopia-An American Ophthalmological Society Thesis.

PURPOSE: To use optical coherence tomography (OCT) to characterize optic nerve head (ONH) peri-neural canal (pNC) scleral bowing (pNC-SB) and pNC choroidal thickness (pNC-CT) in 69 highly myopic and 138 healthy, age-matched, control eyes. DESIGN: Cross-sectional, case control study. METHODS: Within ONH radial B-scans, Bruch membrane (BM), BM opening (BMO), anterior scleral canal opening (ASCO), and pNC scleral surface were segmented. BMO and ASCO planes and centroids were determined. pNC-SB was characterized within 30° foveal-BMO (FoBMO) sectors by 2 parameters: pNC-SB-scleral slope (pNC-SB-SS), measured within 3 pNC segments (0-300, 300-700, and 700-1000 µm from the ASCO centroid); and pNC-SB-ASCO depth relative to a pNC scleral reference plane (pNC-SB-ASCOD). pNC-CT was calculated as the minimum distance between the scleral surface and BM at 3 pNC locations (300, 700, and 1100 µm from the ASCO). RESULTS: pNC-SB increased and pNC-CT decreased with axial length (P < .0133; P < .0001) and age (P < .0211; P < .0004) among all study eyes. pNC-SB was increased (P < .001) and pNC-CT was decreased (P < .0279) in the highly myopic compared to control eyes, and these differences were greatest in the inferior quadrant sectors (P < .0002). Sectoral pNC-SB was not related to sectoral pNC-CT in control eyes, but was inversely related to sectoral pNC-CT (P < .0001) in the highly myopic eyes. CONCLUSIONS: Our data suggest that pNC-SB is increased and pNC-CT is decreased in highly myopic eyes and that these phenomena are greatest in the inferior sectors. They support the hypothesis that sectors of maximum pNC-SB may predict sectors of greatest susceptibility to aging and glaucoma in future longitudinal studies of highly myopic eyes. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.

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.

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.

Can Imaging of Temporal Raphe Orientation with fundusphotos or SD-OCT be helpful for the Assessment of Ocular Torsion in Patients with Cranial Nerve Four Paresis?

Strabismic deviations can be horizontal, vertical, cyclorotational, or a combination of all three. Previous literature has established the difference between subjective and traditional objective torsional angles; however, often there is a failure to consider the physiological position of a normal fovea-optic nerve head (ONH) relationship. Using the temporal raphe (TR) orientation has been suggested as a solution for this discrepancy. The current study, approved by IWK Health Center research ethics board was created to assess the viability of using the TR in assessment of ocular torsion as well as investigate the effect of the physiological position of the fundus. Subjective tests were compared to traditional fundus photographs and novel TR scans in patients with long-standing unilateral fourth nerve palsies. Results found no differences between subjective and objective angles when considering the physiological fundus position and that TR angles were not comparable to other torsional testing methods. Therefore, it was concluded that the physiological position should be considered when determining the true amount of abnormal fundus torsion. As well, we found no significant value to using TR imaging by optical coherence tomography compared to the traditional fovea-ONH relationship by fundus photography to assess ocular torsion.

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.

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.

Peripapillary Scleral Bowing Increases with Age and Is Inversely Associated with Peripapillary Choroidal Thickness in Healthy Eyes.

PURPOSE: To use optical coherence tomography (OCT) to 3-dimensionally characterize the optic nerve head (ONH) in peripapillary scleral bowing in non-highly myopic healthy eyes. DESIGN: Cross-sectional, multicenter study. METHODS: A 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. RESULTS: Both 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. CONCLUSIONS: In 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.

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.

Optical Coherence Tomography Structural Abnormality Detection in Glaucoma Using Topographically Correspondent Rim and Retinal Nerve Fiber Layer Criteria.

PURPOSE: This study evaluated the ability of topographically correspondent (TC) minimum rim width (MRW) and peripapillary retinal nerve fiber layer thickness (pRNFLT) criteria to detect optical coherence tomography (OCT) structural abnormality in glaucoma (GL) and glaucoma suspect (GLS) eyes. DESIGN: Retrospective cross-sectional study. METHODS: A total of 196 GL eyes, 150 GLS eyes, and 303 heathy eyes underwent pRNFL and 24 radial optic nerve head OCT imaging and manual correction of the internal limiting membrane, Bruch's membrane opening (BMO), and outer pRNFL segmentations. MRW and pRNFLT were quantified in 6 Garway-Heath or 12 30-degree (clock-hour) sectors. OCT abnormality for each parameter was defined to be less than the 5th percentile of the healthy eye distribution. OCT abnormality for individual eyes was defined using global, sectoral, and combined parameter criteria that achieved ≥95% specificity in the healthy eyes. TC combination criteria required the sectoral location of MRW and pRNFLT abnormality to be topographically aligned and included comMR (a previously reported TC combination consisting of MRW and pRNFLT parameter: [MRW + pRNFLT × (average MRW healthy eyes/average pRNFLT healthy eyes) MRW]. RESULTS: TC sectoral criteria (1 Garway-Heath MRW + corresponding Garway-Heath RNFLT), (one 30-degree MRW + any 1 corresponding or adjacent 30-degree pRNFLT), 30-degree and Garway-Heath comMR-TI and global comMR were the best performing criteria, demonstrating (96%-99% specificity), 86%-91% sensitivity for GL, 80%-84% sensitivity for early GL (MD ≥ -4.0 dB) and 93%-96% sensitivity for moderate-to-advanced GL (MD < -4.0 dB). CONCLUSIONS: Clinically intuitive TC MRW and pRNFLT combination criteria identified the sectoral location of OCT abnormality in GL eyes with high diagnostic precision.

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.

Influence of Bruch's Membrane Opening Area in Diagnosing Glaucoma With Neuroretinal Parameters From Optical Coherence Tomography.

PURPOSE: To determine whether the glaucoma diagnostic accuracy of age- and Bruch membrane opening area (BMOA)-adjusted normative classifications of minimum rim width (MRW) and retinal nerve fiber layer thickness (RNFLT) is dependent on BMOA, in a European descent population. DESIGN: Retrospective, cross-sectional study. METHODS: We included 182 glaucoma patients and 166 healthy controls for the primary study, and 105 glaucoma patients in a second sample used for a replication study. Optical coherence tomography (Spectralis) measurements of BMOA, global MRW, and RNFLT and normative classifications from the device software were exported for analysis. Sensitivity and specificity were calculated for a conservative criterion (abnormal = "outside normal limits" classification) and a liberal criterion (abnormal = "outside normal limits" or "borderline" classifications). The dependence of sensitivity and specificity on BMOA was analyzed with comparison among subgroups divided by tertiles of BMOA, and with logistic regression. RESULTS: For the conservative criterion, MRW sensitivity was independent of BMOA (P ≥ .76), while RNFLT sensitivity increased in the large BMOA subgroup (P = .04, odds ratio: 1.2 per mm2 [P = .02]). For the liberal criterion, MRW and RNFLT sensitivities were independent of BMOA (P ≥ .53). Specificities were independent of BMOA (P ≥ .07). For the replication sample, which included younger patients with larger BMOA and worse visual field damage than the primary sample, sensitivities were independent of BMOA for both criteria (P ≥ .10). CONCLUSIONS: RNFLT sensitivity was higher in eyes with larger BMOA; however, age and visual field damage may influence that association. MRW diagnostic accuracy was not dependent on BMOA.

OCT-Detected Optic Nerve Head Neural Canal Direction, Obliqueness, and Minimum Cross-Sectional Area in Healthy Eyes.

PURPOSE: To 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. DESIGN: Cross-sectional study. METHODS: After 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. RESULTS: Mean (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). CONCLUSIONS: ASCO/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.

Factors Influencing Optical Coherence Tomography Peripapillary Choroidal Thickness: A Multicenter Study.

Purpose: To 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. Methods: A 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. Results: Globally, 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. Conclusions: In 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.

Outer retinal layer thickness in patients with glaucoma with horizontal hemifield visual field defects.

BACKGROUND/AIMS: To determine the effect of glaucoma on outer retinal layer thickness in eyes with horizontal hemifield visual field (VF) defects. METHODS: We conducted a cross-sectional study in glaucomatous eyes with repeatable (in three or examinations) horizontal hemifield VF (programme 24-2) defect defined as: all five nasal VF locations immediately either above or below the horizontal midline abnormal in the pattern deviation plot with p<0.5%; no mirror-image adjacent 5 VF locations abnormal in the pattern deviation plot and no non-edge VF locations in the non-affected hemifield abnormal in the pattern deviation plot with p<1%. We used optical coherence tomography to measure thickness of each retinal layer in the temporal macula (12° horizontally and 24° vertically) and computed the absolute (µm) and relative (%) intraindividual asymmetry between the perimetrically normal and abnormal hemimacula. RESULTS: We included 10 eyes of 8 patients with median age of 67 years and median VF mean deviation of -8.85 dB. The nerve fibre, ganglion cell and inner plexiform layers were significantly thinner in the perimetrically abnormal hemimacula (median asymmetry of -6.4, -11.5 and -3.8 µm, (corresponding to -27.7, -40.5 and -15.7 %), respectively, all p≤0.01). The inner nuclear layer was slightly thicker in the perimetrically abnormal hemimacula (median asymmetry of 1.3 µm (5.0 %), p=0.01). The outer plexiform, outer nuclear and photoreceptor layers asymmetry values were negligible. CONCLUSION: Our study showed no evidence that glaucoma has an effect on the outer retinal layer thickness. In contrast, a large impact was observed in inner layer thickness.