OCT minimum intensity as a predictor of geographic atrophy enlargement

Abstract

Purpose: We determined whether the minimum intensity (MI) of the optical coherence tomography (OCT) A-scans within the retina can predict locations of growth at the margin of geographic atrophy (GA) and the growth rate outside the margin.

Methods: The OCT scans were analyzed at baseline and 52 weeks. Expert graders manually segmented OCT images of GA. The 52-week follow-up scans were registered to the baseline scan coordinates for comparison. The OCT MI values were studied within a 180-μm margin around the boundary of GA at baseline. Baseline MI values were compared in areas of progression and nonprogression of the GA, and sensitivity and specificity were assessed for prediction of growth at the margin. Average MI values in the margins were compared to overall growth rates to evaluate the prediction of growth outside the margins.

Results: A statistically significant increase in MI (P < 0.05) was seen in areas of growth in 21/24 cases (88%), and 22/24 cases (92%) when the foveal subfield was excluded. Locations of growth within the margins at 52 weeks were predicted with 61% sensitivity and 61% specificity. The MI values correlated significantly with overall growth rate, and high and low growth rate subjects were identified with 80% sensitivity and 64% specificity.

Conclusions: The MI may be increased at the margins of GA lesions before enlargement, which may indicate disruption or atrophy of the photoreceptors in these areas before GA becomes apparent. Increased MI may help predict areas of enlargement of GA, and may relate to overall growth rate and be a useful screening tool for GA. (ClinicalTrials.gov number, NCT00935883.).

Keywords: AMD; GA; geographic atrophy; image processing; macula.

Figure 1

Subretinal pigment epithelium slab image. Axial integration highlights areas of illumination below the RPE.

Figure 2

Manual segmentation of subretinal pigment epithelium slab images. (A) Image derived from baseline OCT scan. (B) Image derived from OCT scan performed after 52 weeks.

Figure 3

Construction of the MI image. (A) The same baseline OCT scan that was used for the subretinal pigment epithelium slab in Figure 2A was used to identify minima (red circles) from each speckle-reduced B-scan. (B) The minimum intensities were assembled into an en face image. Contrast of the en face image was enhanced.

Figure 4

Extraction of MI values from areas of progression and nonprogression at the edge of GA. (A) MI image from the initial baseline scan, with the area of GA at baseline outlined in red. The GA segmentation was obtained from the baseline scan sub-RPE slab. (B) The yellow line depicts the 180-μm perimeter around the baseline perimeter of the GA segmentation (red). The red and yellow contours enclose the area to be analyzed. (C) The area of GA at 52-week follow-up is outlined in green. The segmentation of the 52-week sub-RPE slab was registered to the position of the initial baseline scan. (D) Areas of 52-week progression (red) and nonprogression (black) are found within the 180-μm perimeter of the baseline GA segmentation. Pixels are downsampled by 2 in each direction to eliminate statistical dependence due to smoothing of adjacent pixels.

Figure 5

Histogram of normalized baseline MIs within 180 μm of edge of GA from baseline scan for a typical case. While there is a large overlap between the MIs of the areas within the 180-μm border region that later progressed to GA and of those that did not, on the whole there was significant increase (P < 0.01) for this eye in areas that later progressed to GA.

Figure 6

Example of an en face MI image from baseline OCT scan, with selected B-scan showing locations of minima, area of increased MI at baseline, area of GA at baseline, and area of GA at 52-week follow-up. (A) En face OCT MI image. Red outline indicates GA segmentation determined using sub-RPE slab from this same OCT data volume. Green outline indicates GA segmentation determined using sub-RPE slab from 52-week follow-up OCT scan, registered into coordinates of the scan shown here. Light blue outline indicates region of increased MI determined by thresholding the MI image. Red dashed line indicates location of selected B-scan. (B) Speckle-reduced B-scan, zoomed vertically. Points of increased MI (determined by thresholding the en-face MI image) in light blue; points of normal MI in dark blue. Red bracket indicates the GA segmentation determined using sub-RPE slab from this same OCT data volume. Green bracket indicates the registered GA segmentation from the 52-week follow-up scan. In this example, the region of increased MI includes the region of 52-week progression and slightly beyond. In this B-scan, all minima that occur above the ONL and HFL, indicating disruption of those layers, are contained within the region of increased MI.

Figure 7

En face MI image from baseline OCT scan, with selected B-scan. (A) En face OCT MI image, showing that the MI at the fovea is lower than that of the surrounding area of GA. See Figure 6 for descriptions of color coding. (B) Speckle-reduced B-scan, zoomed vertically.

Figure 8

Analysis of sensitivity and specificity of the MI prediction of growth within the 180-μm border region at 52 weeks. The ROC curve plots true positive fraction (sensitivity) versus false positive fraction (1 − specificity) for the full range of possible threshold values. Here we plot the true positive and false positive fractions resulting from the range of thresholds on MI_relative, the average MI in the 180-μm margin measured relative to the average minimum intensities found in the lesion and background regions. (A) Using all data, including the fovea, a threshold value of 0.50 (indicated by red circle), predicted locations of growth with 61% sensitivity and 61% specificity. (B) Excluding the fovea from the analysis still gave 61% sensitivity and 61% specificity at a threshold value of 0.50.

Figure 9

Scatterplots of overall growth rate versus relative MI (MI_relative) at the margin of GA. (A) Scatterplot including foveal data. (B) Scatterplot excluding foveal data.

Figure 10

Scatterplots of overall growth rate versus relative MI (MI_relative) at the margin of GA for groups separated into above- and below-average growth rates. Green regions indicate areas of correct prediction, where MI_relative > 0.5 corresponded to an above-average growth rate or MI_relative < 0.5 corresponded to a below-average growth rate; white regions indicate areas of incorrect prediction. Large numbers indicate the number of subjects in each region. (A) Scatterplot including foveal data. (B) Scatterplot excluding foveal data.