Quantitative comparison of drusen segmented on SD-OCT versus drusen delineated on color fundus photographs

Abstract

Purpose: Spectral domain-optical coherence tomography (SD-OCT) may be useful for efficient measurement of drusen in patients with age-related macular degeneration (AMD). Areas identified as drusen from semiautomated segmentation of drusen on SD-OCT were compared to those identified from review of digital color fundus photographs (CFPs).

Methods: Twelve eyes with nonneovascular AMD were prospectively imaged with digital CFP and SD-OCT. For each eye, areas on CFP in which at least two of three retina specialists agreed on drusen presence produced the composite CFP drusen map. Automated image analysis produced another CFP map. Areas identified as drusen by segmentation on SD-OCT B-scans were plotted as the SD-OCT drusen map. The CFP and SD-OCT maps were compared and agreement was quantified. Disagreement was characterized into distinct types, and the frequency of each type was quantified.

Results: There was general agreement between CFP and SD-OCT in identifying presence and absence of drusen, with mean agreement in 82% ± 9% of total image pixels. Most disagreement (80% ± 15%) occurred at drusen margins. There was a trend toward greater detection of drusen with SD-OCT in eyes with larger drusen and with hyperpigmentation. There was a trend toward greater detection of smaller drusen by CFP.

Conclusions: Good agreement was demonstrated in drusen detection between CFP and SD-OCT. Areas of disagreement underscore limitations of CFP-based measurement of drusen, particularly in the sizing of large, soft drusen. SD-OCT shows great promise as an adjunctive tool for assessing drusen burden in AMD. (ClinicalTrials.gov number, NCT00734487.).

Figure 1.

SD-OCT volume scan with SVP representation. B-scans (A), taken sequentially at a fixed azimuthal interval (66 μm) across the macula, form a volume scan (B). The three-dimensional appearance of drusen becomes apparent with volume scanning. The volume scan can be collapsed axially, with averaging of pixel intensity, to form the en face SVP retinal image (C).

Figure 2.

Drusen maps for study eye 3. Three retinal specialists independently graded the CFP (unmarked in A) for drusen (B–D). A composite CFP drusen map, representing all areas marked as drusen by at least two of three graders, is represented as (E). To create a projection map of drusen from SD-OCT scans, interpolation of sequential OCT B-scans must be performed. This is because the 6.6 × 6.6-mm field-of-view is sampled by 100 OCT B-scans. Whereas the field of view is represented by 1000 × 1000 pixels in the CFP images (A), there are only 100 × 1000 pixels in the projected OCT markings. (F, G) The interpolated OCT markings using a 2-D cubic interpolation function (MatLab; The MathWorks) and NWE interpolation. Unless otherwise stated, the NWE interpolation (G) was used for comparative analysis in this study.

Figure 3.

Automated segmentation of drusen on CFP. The original image (A) demonstrates poorly defined drusen and pigmentation variations. The image is first enhanced and color balanced, and the drusen region of interest is interactively selected (B). The mathematical model for the image background (contour graph, C) is calculated in commercial software (MatLab; The Mathworks). On the background-leveled image (D), the drusen detection algorithm identifies multiple drusen (green).

Figure 4.

Maximum drusen size within the central study area for subject 6. Maximum drusen size is defined as the greatest linear span of contiguous drusen. (A) Unmarked CFP; (B, C) composite CFP and SD-OCT drusen maps, respectively, with a line indicating maximum drusen size for each drusen map.

Figure 5.

Bland-Altman plot for agreement between SD-OCT-based and composite CFP-based measurement of total drusen area within the central macular area in 12 subjects with AREDS category 3 nonneovascular AMD. To obtain this plot, the difference in total drusen area as measured with SD-OCT (NWE interpolation) and composite CFP was plotted against the mean drusen area of the two measurements for each subject. A modified Bland-Altman plot, using a regression approach for nonuniform differences, accounts for the positive correlation between difference in measured drusen area and mean drusen area. The regression line is displayed along with the upper and lower 95% limits of agreement.

Figure 6.

ICC for total drusen area measurement for pairs of grading modalities, along with confidence intervals.

Figure 7.

Mean agreement and disagreement for grading of drusen by SD-OCT (NWE interpolation) and composite (agreement by any two of three graders) CFP. Data reported include mean percentage of pixels (±SD) marked as drusen by both SD-OCT and composite CFP, neither SD-OCT nor CFP, SD-OCT but not CFP, and CFP but not SD-OCT.

Figure 8.

Disagreement in marking of drusen between the SD-OCT (NWE interpolation) versus composite CFP (agreement by any two of three graders) drusen maps. (A) Pixels identified as drusen by composite CFP but not SD-OCT; (B) pixels identified as drusen by SD-OCT but not CFP; (C) color coding of pixels by various subtypes of disagreement (see Table 3).

Figure 9.

Types of disagreement in drusen identification by SD-OCT and CFP. Left column: CFPs for representative examples of disagreement, each with an outline indicating location of the corresponding B-scan. Middle column: the SD-OCT B-scan for each sample, with brackets identifying the region of disagreement. Right column: the same fundus photo with either the SD-OCT map (F, I) or composite CFP drusen map (C, L, O) in black, superimposed with color markings representing all areas of the specified disagreement type (see Table 3): (A–C) type IA, undermarking of drusen borders by CFP; (D–F) type IB, undermarking of drusen borders by SD-OCT; (G–I) type II, hypopigmentation with appearance of drusen without a corresponding OCT finding; (J–L) type III, pigmentary migration with obscuration of underlying drusen; and (M–O) type IV, OCT deflection without corresponding CFP pigmentary change. (Not pictured: type IC, nonspecific disagreement at drusen borders.)

Figure 10.

Disagreement types IA and IB, represented as a percentage of the total area of interest, are plotted against total drusen area (average of SD-OCT- and CFP-based measurements) for each of 12 subjects (see also Fig. 9, Table 3).

Figure 11.

The lines on the CFP (A) highlight an area marked as drusen by all three CFP graders, just outside the central macular area of interest. The corresponding SD-OCT B-scan (B) did not reveal drusen at this location, highlighted with brackets.