Matching Misaligned Spectralis OCTs to a Reference Scan in Pediatric Glaucoma with Poor Fixation and Nystagmus

Abstract

Purpose: Poor fixation or nystagmus in children causes misalignment errors when measuring circumpapillary retinal nerve fiber layer (cpRNFL) thickness by simultaneous scanning laser ophthalmoscope imaging/optical coherence tomography (SLO/OCT). We investigated a method to assess cpRNFL from misaligned SLO/OCT scans.

Methods: Heidelberg Spectralis SLO/OCT scans from a single clinical examination were retrospectively analyzed when automated eye tracking was unreliable. Retinal layer thickness was measured at overlapping match locations between a reference and misaligned scans based on the position data from simultaneously acquired SLO images. Three layers were segmented: cpRNFL, internal limiting membrane to outer nuclear layer (ILM-ONL), and total retinal thickness (TR). Accuracy was defined as the difference in thickness between the reference and misaligned scans at their match locations after correction for scan angle.

Results: Thirty-five subjects, evaluated for glaucomatous nerve loss, met inclusion criteria. Group-averaged accuracy was -2.7, 1.4, and 0.3 µm for cpRNFL, ILM-ONL, and TR thickness, respectively. Across all layers, interobserver intraclass correlation coefficients ranged from 0.97 to 0.63 and the maximum Bland-Altman 95% limits of agreement were -21.6 to 20.7 µm. Variability was greatest for cpRNFL thickness and least for TR thickness. Increased variability was associated with lower signal-to-noise ratio but not with image-motion indices of shear, rotation, and scale.

Conclusions: Retinal layer thickness can be compared to a reference cpRNFL OCT scan when poor fixation and nystagmus causes misalignment errors. The analysis can be performed post hoc using multiple misaligned scans from standard SLO/OCT protocols.

Translational relevance: Our method allows for assessment of cpRNFL in children who fail eye tracking.

Keywords: nystagmus; optic nerve; optical coherence tomography; pediatric ophthalmology.

Figure 1.

Simulation of circumpapillary scan positions over time in 3 subjects with different levels of fixation. The left side shows the same SLO image with a circumpapillary reference scan (blue circle) placed at identical positions. In (A), the child with stable fixation maintains circumpapillary scan positions near the reference scan at velocities < 20 degrees/second (green circles, color coded by velocity). (B) A subject with moderate amplitude nystagmus would have poor positioning with respect to the reference scan due to both horizontal and vertical eye movements. (C) Subject with large amplitude nystagmus and re-fixation saccades have large variation in scan locations and eye velocity such that accurate positioning is not possible for the entire recording. Traces to the right are corresponding video-oculography recordings of horizontal (H) and vertical (V) eye movement positions. For the horizontal trace, upward deflections are rightward movements and downward deflections are leftward movements. For the vertical trace, upward deflections are upward movements and downward deflections are downward movements. The fovea position is determined manually when it is visible (blue square).

Figure 2.

Schematic of the methodology. Top, a reference SLO/OCT scan is selected for each subject and is segmented into three layers by the software as shown by control points (red dots on OCT image) with spline fitting. At right the thickness of the retinal nerve fiber layer serves as a standard for comparisons and is plotted on the Spectralis normative template. The software stores a copy of the optic disc image, centered on the reference circumpapillary scan, and uses the image to find its location on all other misaligned scans (center of the match location is shown by the orange box). The match of the optic disc determines where the reference scan would lie on all other scans and is also used to quantify image distortion due to eye movements. The software then finds matching loci on the SLO image between the reference scan (green circle) with the misaligned OCT scan position (blue circle). The match regions on the SLO are indicated by arrows, while the red regions show the corresponding matching locations on the OCT (right side). The user ensures that layer segmentation is accurate only in the highlighted red regions as these locations will be analyzed. Layer thickness for matching regions are accumulated across subsequent misaligned OCT scans, which are then plotted along with the reference (gray line) in the bottom plot. The difference in thickness between the reference and all misaligned scans are used to assess accuracy. Note, not all data are shown for clarity.

Figure 3.

Accuracy of the analysis represented by average difference in retinal layer thickness of misaligned scans from the reference scan. The top plot shows differences for the RNFL. The middle plot shows differences for the thickness from the ILM-ONL. The bottom plot shows differences for total retinal thickness from ILM to Bruch's membrane (TR). Individual subjects are plotted along the abscissa and the group mean on the right. Error bars are 1 standard deviation of the difference. The dotted line is the ideal outcome of 0.0.

Figure 4.

Mean of absolute difference in retinal layer thickness between match locations on misaligned scans and the corresponding reference scan with respect to relative circumpapillary scan angle. Black columns represent RNFL. Gray columns represent ILM-ONL. White columns represent total retinal thickness from ILM to Bruch's membrane (TR). The plot is based on data from all subjects, with a minimum of 600 data points for each column.

Figure 5.

Bland-Altman plots showing comparisons between two observers for scoring mean RNFL and (B) mean total retinal (TR) thickness. The top row (A, B) shows comparisons between reference images. The bottom row (C, D) shows comparisons of matched locations on misaligned images. The solid line indicates the average difference, the dashed lines indicate the 95% limits of agreement. The shaded boxes represent the 95% CI on bias, upper, and lower limits of agreement. All data points were matched for circular scan angle with respect to the fovea.

Figure 6.

Examples of measurement errors of RNFL thickness from matching locations on misaligned circumpapillary scans (black points) compared to the reference scan (gray points). Data from subject 7 are plotted in (A), whereas data from subject 29 are plotted in (B). Arrows point to areas with large errors likely related to motion artefact occurring between acquisition times of the OCT with respect to the corresponding SLO image.