Detecting Progression in Advanced Glaucoma: Are Optical Coherence Tomography Global Metrics Viable Measures?

SIGNIFICANCE: Optical coherence tomography (OCT) summary measures have been suggested as a way to detect progression in eyes with advanced glaucoma. Here, we show that these measures have serious flaws largely due to segmentation errors. However, inspection of the images and thickness maps can be clinically useful. PURPOSE: This study aimed to test the hypothesis that recently suggested global OCT measures for detecting progression in eyes with advanced progression are seriously affected by segmentation mistakes and other errors that limit their clinical utility. METHODS: Forty-five eyes of 38 patients with a 24-2 mean deviation worse than -12 dB had at least two spectral domain OCT sessions (0.8 to 4.4 years apart) with 3.5-mm circle scans of the disc and cube scans centered on the fovea. Average (global) circumpapillary retinal nerve fiber layer thickness, GcRNFL, and ganglion cell plus inner plexiform layer thickness, GGCLP, were obtained from the circle and cube scan, respectively. To evaluate progression, ΔGcRNFL was calculated for each eye as the GcRNFL value at time 2 minus the value at time 1, and ΔGGCLP was calculated in a similar manner. The b-scans of the six eyes with the highest and lowest ΔGcRNFL and ΔGGCLP values were examined for progression as well as segmentation, alignment, and centering errors. RESULTS: Progression was a major factor in only 7 of the 12 eyes with the most negative values of either ΔGcRNFL or ΔGGCLP, whereas segmentation played a role in 8 eyes and was the major factor in all 12 eyes with the largest positive values. In addition, alignment (one eye) and other (three eyes) errors played a secondary role in four of the six eyes with the most negative ΔGcRNFL values. CONCLUSIONS: For detecting the progression of advanced glaucoma, common summary metrics have serious flaws largely due to segmentation errors, which limit their utility in clinical and research settings.

Global optical coherence tomography measures for detecting the progression of glaucoma have fundamental flaws.

OBJECTIVE: To understand the problems involved in using global OCT measures for detecting progression in early glaucoma. SUBJECTS/METHODS: Eyes from 76 patients and 28 healthy controls (HC) had a least two OCT scans at least 1 year apart. To determine the 95% confidence intervals (CI), 151 eyes (49 HC and 102 patients) had at least two scans within 6 months. All eyes had 24-2 mean deviation ≥-6dB. The average (global) thicknesses of the circumpapillary retinal nerve fibre layer (cRNFL), GONH, and of the retinal ganglion cell layer plus inner plexiform layer (RGCLP), Gmac, were calculated. Using quantile regression, the 95% CI intervals were determined. Eyes outside the CIs were classified as "progressors." For a reference standard (RS), four experts evaluated OCT and VF information. RESULTS: Compared to the RS, 31 of the 76 (40.8%) patient eyes were identified as progressors (RS-P), and 45 patient, and all 28 HC, eyes as nonprogressors (RS-NP). The metrics missed (false negative, FN) 15 (48%) (GONH) and 9 (29%) (Gmac) of the 31 RS-P. Further, GONH and/or Gmac falsely identified (false positive, FP) 10 (22.2%) of 45 patient RS-NP eyes and 7 (25%) of the 28 HC eyes as progressing. Post-hoc analysis identified three reasons (segmentation, centring, and local damage) for these errors. CONCLUSIONS: Global metrics lead to FPs and FNs because of problems inherent in OCT scanning (segmentation and centring), and to FNs because they can miss local damage. These problems are difficult, if not impossible, to correct, and raise concerns about the advisability of using GONH and Gmac for detecting progression.

Reasons why OCT Global Circumpapillary Retinal Nerve Fiber Layer Thickness is a Poor Measure of Glaucomatous Progression.

Purpose: To assess the effects of local defects, segmentation errors, and improper image alignment on the performance of the commonly used optical coherence tomography (OCT) measure of progression, that is the change in global (average) circumpapillary retinal nerve fiber layer (cpRNFL) thickness (ΔG). Methods: One hundred fifty eyes suspected of, or with, early glaucoma had OCT circle and cube scans obtained using eye tracking on two occasions at least 1 year apart. Statistical progression was defined by fixed values of ΔG (3-8 um) and quantile regression. For a reference standard, four authors identified 30 eyes as "likely progressed," and 61 eyes that "likely had not progressed" based on OCT reports from both baseline and follow-up tests. Results: A ΔG criterion of 4 um had the best accuracy: 77%, with 5 false positive (8.2%) and 16 false negative (53%). A post hoc analysis of circular b-scans and OCT probability maps of these eyes indicated that segmentation errors and local progression accounted for most of these mistakes. Segmentation errors, although less common, were also present in true positives and true negatives. Conclusions: Local defects and segmentation errors are the primary reasons for the poor performance of cpRNFL thickness G metric. Because these problems are difficult, if not impossible, to eliminate, the G metric should not be relied on in isolation for detecting glaucomatous progression. Translational Relevance: Local defects and segmentation errors are easily identified by viewing OCT circumpapillary images, which should be part of the standard protocol for detecting glaucomatous progression.

Local Glaucomatous Defects of the Circumpapillary Retinal Nerve Fiber Layer Show a Variety of Patterns of Progression.

PRECIS: The region of glaucomatous progression, seen on optical coherence tomography (OCT) images of the circumpapillary retinal nerve fiber layer (cRNFL), increases in width and depth in all eyes, but shows a variety of different patterns of loss across eyes. PURPOSE: The purpose of this study was to examine the patterns of cRNFL loss secondary to glaucomatous progression in a region associated with the superior hemifield of the 24-2/30-2 visual field (VF). METHODS: Twenty-four eyes (20 patients) with a diagnosis of glaucoma and evidence of progression on OCT had OCT disc cube scans on at least 3 separate visits (mean follow-up 7.4 y; range: 3.9 to 11.4). Circumpapillary b-scans were derived after enface images were aligned to assure that the study region (ie, 0 to -135 degrees, where 0 degree is 9 o'clock, on a right eye) coincided. Within this region, a region of progression (ROP) was defined based on the loss in cRNFL thickness between the first and subsequent visits. The width of the ROP was determined, along with the locations of its leading (close to fixation) and trailing edges. In addition, for each ROP, the location and depth at the point of maximal loss, total loss, and average remaining retinal nerve fiber layer were measured. RESULTS: The ROP proceeded both toward and away from fixation. Across eyes, the ROP varied widely in width (32 to 131 degrees, mean 82.7 degrees), location, and loss at point of deepest loss (22 to 99 µm, mean 52.9 µm), as well as total cRNFL loss. CONCLUSIONS: All eyes showed a widening and deepening of the ROP, but a variety of different patterns of progressive cRNFL loss. Thus, one should expect considerable variation in patterns of VF loss. Furthermore, conventional metrics (global or quadrant cRNFL thickness) do not fully depict the progressive changes that can be appreciated by inspecting OCT images.