Central Macular Topographic and Volumetric Measures: New Biomarkers for Detection of Glaucoma.

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

Ganglion Cell Complex: The Optimal Measure for Detection of Structural Progression in the Macula.

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

Detection of Longitudinal Ganglion Cell/Inner Plexiform Layer Change: Comparison of Two Spectral-Domain Optical Coherence Tomography Devices.

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