Drusen ultrastructure imaging with spectral domain optical coherence tomography in age-related macular degeneration

Abstract

Purpose: To categorize drusen ultrastructure in age-related macular degeneration (AMD) using spectral domain optical coherence tomography (SDOCT) and correlate the tomographic and photographic drusen appearances.

Design: Prospective case series.

Participants: Thirty-one eyes of 31 patients with non-neovascular AMD.

Methods: Subjects with drusen and a clinical diagnosis of AMD were enrolled in an SDOCT imaging study from August of 2005 to May of 2007. Foveal linear scans were acquired, and the image data were processed for analysis. Drusen were scored by 4 morphologic categories: shape, predominant internal reflectivity, homogeneity, and presence of overlying hyper-reflective foci. The prevalences of each morphologic pattern and combinations of morphologic patterns observed were calculated. The photographic appearance of each druse was compared with the tomographic classification. Interobserver and intraobserver agreement analysis was performed.

Main outcome measures: Prevalence of morphologic parameters using SDOCT.

Results: Twenty-one eyes of 21 patients had SDOCT B-scans of adequate quality for analysis. On the basis of the above morphologic categories, 17 different drusen patterns were found in 120 total drusen. The most common was convex, homogeneous, with medium internal reflectivity, and without overlying hyper-reflective foci, present in 17 of 21 eyes (81%). Of the 16 eyes (76%) with nonhomogeneous drusen, 5 had a distinct hyper-reflective core. Hyper-reflective foci overlying drusen were in 7 eyes (33%). Although half of the photographically soft-indistinct drusen were convex with medium internal reflectivity and homogeneous without overlying hyper-reflective foci, the other half had significant variability in their tomographic appearance. Both interobserver and intraobserver agreement in drusen grading were high. Readers agreed the most when grading drusen shape and reflectivity, whereas the least agreement was for drusen homogeneity.

Conclusions: Drusen ultrastructure can be imaged with SDOCT and characterized with a simple grading system. Photographic appearance may predict some but not all tomographic appearances. Trained observers have a high level of agreement with this grading system. These in vivo morphologic characteristics imaged with SDOCT may be distinct subclasses of drusen types, may relate closely to ultrastructural drusen elements identified in cadaveric eyes, and may be useful imaging biomarkers for disease severity or risk of progression. This will require validation from further studies.

Figure 1

Two unprocessed (non-summed) scans and a registered, summed scan produced from the processed stack are compared. (A, B) Two raw linear SDOCT B-scans before summing and registration. (C) A registered and summed linear SDOCT B-scan. Considerable variability in drusen morphology in a single linear scan is demonstrated. (D) Color fundus photograph corresponding to above SDOCT scans. Line shows location of SDOCT scans. Observed drusen are numbered.

Figure 2

The 17 combined morphologic drusen patterns observed: (A) Pattern 1: concave, low reflectivity, nonhomogeneous without core, no overlying foci. (B) Pattern 2: concave, low reflectivity, nonhomogeneous with core, overlying foci. (C) Pattern 3: concave, medium reflectivity, homogeneous, no overlying foci. (D) Pattern 4 (marked with *): concave, medium reflectivity, nonhomogeneous without core, no overlying foci. (E) Pattern 5 (marked with *): concave, medium reflectivity, nonhomogeneous without core, overlying foci. (F) Pattern 6 (marked with *): concave, high reflectivity, homogeneous, no overlying foci. (G) Pattern 7: convex, low reflectivity, nonhomogeneous with core, overlying foci. (H) Pattern 8: convex, medium reflectivity, homogeneous, no overlying foci. (I) Pattern 9: convex, medium reflectivity, homogeneous, overlying foci. (J) Pattern 10: convex, medium reflectivity, nonhomogeneous without core, no overlying foci. (K) Pattern 11: convex, medium reflectivity, nonhomogeneous with core, no overlying foci. (L) Pattern 12: convex, medium reflectivity, nonhomogeneous without core, overlying foci. (M) Pattern 13: convex, medium reflectivity, nonhomogeneous with core, overlying foci. (N) Pattern 14 (marked with *): convex, high reflectivity, homogeneous, no overlying foci. (O) Pattern 15 (marked with *): convex, high reflectivity, nonhomogeneous without core, no overlying foci. (P) Pattern 16 (marked with *): convex, high reflectivity, nonhomogeneous without core, overlying foci. (Q) Pattern 17: saw-tooth, no overlying foci.

Figure 3

(A) Linear SDOCT scan to correlate soft-indistinct drusen with the tomographic appearance on SDOCT. Druse 4 has a spot of increased pigmentation that may be represented by the hyper-reflective foci seen in (B). Druse 5 from the SDOCT B-scan is not visualized on the color photograph. (B) Corresponding linear SDOCT B-scan. Although all the visualized drusen in the photograph are soft-indistinct, there is considerable variability in shape, predominant internal reflectivity, homogeneity, and the presence of hyper-reflective foci.

Figure 4

(A) Linear scan through fovea superimposed on color photograph to correlate soft-indistinct drusen type with tomographic appearance. (B) Corresponding linear SDOCT B-scan.

Figure 5

(A) Linear scan through fovea superimposed on color photograph to correlate a calcific druse (5) type with tomographic appearance. (B) Corresponding linear SDOCT B-scan.