To test the hypothesis that the amount and distribution of glaucomatous damage along the entire retinal ganglion cell–axonal complex (RGC-AC) can be quantified and to map the RGC-AC connectivity in early glaucoma using automated image analysis of standard spectral-domain optical coherence tomography.
Spectral-domain optical coherence tomography volumes were obtained from 116 eyes in 58 consecutive patients with glaucoma or suspected glaucoma. Layer and optic nerve head (ONH) analysis was performed; the mean regional retinal ganglion cell layer thickness (68 regions), nerve fiber layer (NFL) thickness (120 regions), and ONH rim area (12 wedge-shaped regions) were determined. Maps of RGC-AC connectivity were created using maximum correlation between regions' ganglion cell layer thickness, NFL thickness, and ONH rim area; for retinal nerve fiber bundle regions, the maximum “thickness correlation paths” were determined.
The mean (SD) NFL thickness and ganglion cell layer thickness across all macular regions were 22.5 (7.5) μm and 33.9 (8.4) μm, respectively. The mean (SD) rim area across all ONH wedge regions was 0.038 (0.004) mm2. Connectivity maps were obtained successfully and showed typical nerve fiber bundle connectivity of the RGC-AC cell body segment to the initial NFL axonal segment, of the initial to the final RGC-AC NFL axonal segments, of the final RGC-AC NFL axonal to the ONH axonal segment, and of the RGC-AC cell body segment to the ONH axonal segment.
In early glaucoma, the amount and distribution of glaucomatous damage along the entire RGC-AC can be quantified and mapped using automated image analysis of standard spectral-domain optical coherence tomography. Our findings should contribute to better detection and improved management of glaucoma.
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Figure 1. Registered projection image overlaid with the nerve fiber bundle grid showing regions (1, 1) through (12, 10) (white), the macular grid (regions 1-68 [cyan]), the optic nerve head grid that includes the optic cup regions (regions a through l [orange]), and the optic nerve head wedge regions (regions A through L [green]). The green and red cross marks show the foveal center and the neural canal opening centroid, respectively. The nerve fiber bundle grid has been slightly tilted, which decreased the thickness variability in preliminary studies. The scaling factor d is the distance between the fovea and the center of the neural canal opening.
Figure 2. Segmentation of the nerve fiber layer (NFL), ganglion cell layer (GCL) and combined layer of the outer segment (OS) and retinal pigment epithelium (RPE) from macular and peripapillary spectral-domain optical coherence tomography volumes. A, Flattened and cropped B-scan image of the macular spectral-domain optical coherence tomography volume. B, Image A overlaid with the layer segmentation results. C, Three-dimensional rendering of the surfaces segmented in B. D, Flattened and cropped B-scan image of the peripapillary spectral-domain optical coherence tomography volume. E, Image D overlaid with the layer segmentation results. F, Three-dimensional rendering of the surfaces segmented in image E. N indicates nasal; RPE*, RPE complex; and T, temporal.
Figure 3. Segmentation of the optic cup, neuroretinal rim, and neural canal opening from the peripapillary spectral-domain optical coherence tomography volume. A, Flattened and cropped B-scan image. B, Image A overlaid with the cup (green regions) and rim (red region) segmentation results. The neural canal opening segmentation result is the combined region of the cup and rim. C, Spectral-domain optical coherence tomography projection image. D, Image C overlaid with the cup and rim segmentation results.
Figure 4. Retinal ganglion cell–axonal complex connectivity maps for the cell body segment (in the ganglion cell layer) to the optic nerve head neural rim segment. Shown are color-coded correspondence (A) and highest r2 value (B) maps.
Figure 5. Scatterplots for the highest r2 values between the regional mean macular ganglion cell layer thickness (x-axis, 0-80 μm) and the regional optic nerve head rim area (y-axis, 0-0.15 mm2).
Figure 6. Emergent retinal ganglion cell–axonal complex connectivity maps overlaid on a registered projection image from a single patient for illustrative purposes. A, Connectivity from the macular ganglion cell layer regions to “close” initial nerve fiber bundle regions. The arrow starting in each macular grid region ends at one of 5 × 5 neighboring nerve fiber bundle grid regions that exhibits the maximum Pearson product moment correlation coefficient as indicated by the color of the arrow. A dot located in a specific grid square denotes that the highest correlation was between the macular and nerve fiber bundle regions in the same location. B, Connectivity from the most nasal nerve fiber bundle regions to the optic nerve head wedge regions. The nerve fiber bundle region and the optic nerve head wedge region exhibiting the maximum r2 values are coded with the same color. C, Same as B except that the pseudocolors show their maximum r2 value. D, Connectivity of individual nerve fiber bundle regions (retinal ganglion cell–axonal complex segments in the nerve fiber layer) from the initial (anywhere in the nerve fiber bundle grid) to the most nasal nerve fiber bundle grid regions. The line starting from each nerve fiber bundle grid region (except for the most nasal regions) and ending at one of the most nasal nerve fiber bundle regions is the minimum cost path, or the highest overall correlation among all possible nerve fiber bundle segment nerve fiber layer thicknesses. The color shows the starting position in the nerve fiber bundle grid. The top and bottom paths follow the top and bottom boundaries of the nerve fiber bundle grid because information is available outside the registered spectral-domain optical coherence tomography images. E, Same as D except that the color shows the aggregate Pearson product moment correlation coefficient of the nerve fiber bundle region nerve fiber layer thicknesses.
Figure 7. Connectivity map from the macular regions to the initial nerve fiber bundle regions as in Figure 6A but based on left eye spectral-domain optical coherence tomography data only. The overall pattern of connections is similar to that shown in Figure 6A, but the connectivity is more noisy based on half the data as in Figure 6A. Similar results were obtained for the left eye only that corresponded to the other panels in Figure 6.
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