Imaging of the retinal pigment epithelium in age-related macular degeneration using polarization-sensitive optical coherence tomography

Abstract

Purpose. Spectral-domain optical coherence tomography (SD-OCT) provides new insights into the understanding of age-related macular degeneration (AMD) but limited information on the nature of hyperreflective tissue at the level of the retinal pigment epithelium. Therefore, polarization-sensitive (PS) SD-OCT was used to identify and characterize typical RPE findings in AMD. Methods. Forty-four eyes of 44 patients with AMD were included in this prospective case series representing the entire AMD spectrum from drusen (n = 11), geographic atrophy (GA; n = 11), neovascular AMD (nAMD; n = 11) to fibrotic scars (n = 11). Imaging systems were used for comparative imaging. A PS-SD-OCT instrument was developed that was capable of recording intensity and polarization parameters simultaneously during a single scan. Results. In drusen, PS-SD-OCT identified a continuous RPE layer with focal elevations. Discrete RPE atrophy (RA) could be observed in two patients. In GA, the extension of the RA was significantly larger. Residual RPE islands could be detected within the atrophic zone. PS-SD-OCT identified multiple foci of RPE loss in patients with nAMD and allowed recognition of advanced RPE disease associated with choroidal neovascularization. Wide areas of RA containing residual spots of intact retinal pigment epithelium could be identified in fibrotic scars. Conclusions. PS-SD-OCT provided precise identification of retinal pigment epithelium in AMD. Recognition of these disease-specific RA patterns in dry and wet forms of AMD is of particular relevance to identify the status and progression of RPE disease and may help to better estimate the functional prognosis of AMD.

Figure 1

This figure show how the following notations were generated in a patient with drusen and used to visualize intensity-based information in combination with polarization-scrambling properties of the RPE. The “intensity” image (A) shows the typical elevations of the retinal pigment epithelium well known from standard OCT technology, whereas the “retardation” image (B) shows a greenish band that is caused by the random retardation values from speckle to speckle. This information can clearly be associated with the retinal pigment epithelium (the color scale contains values between blue [0° retardation] and red [90° retardation]). The calculated DOPU image (C) shows an even better contrast of the retinal pigment epithelium in comparison with other structures of the retina (red, DOPU = 1; black, DOPU = 0). A composite image can be generated (D) showing the segmented retinal pigment epithelium (red line) projected on a normal intensity image. This approach demonstrates the performance of the automated segmentation algorithm using the DOPU information in comparison with the RPE appearance in the intensity image.

Figure 2

Comparison of different OCT devices in drusen. Current SD-OCT instruments (C–K) are clearly superior to conventional time-domain OCT (A, B). Although the segmentation algorithms provided by OCT systems detect elevations of the retinal pigment epithelium correctly (E, H), they fail to detect FSLs of the retinal pigment epithelium, suggesting a continuous RPE pattern in this patient. The Spectralis OCT shows brilliant B-scan quality (I) but fails to segment the retinal pigment epithelium reliably (J). The autofluorescence image does not show a significant defect of the retinal pigment epithelium (K). PS-SD-OCT identifies the retinal pigment epithelium precisely (L) and visualizes small FSLs in the retinal pigment epithelium in the retinal thickness map (M) and in the RPE map (N). FSLs are indicated by arrows in (N) and are displayed in gray in the PS-SD-OCT–derived retinal thickness (M) and RPE elevation (N) maps.

Figure 3

Representative B-scan (same eye as in Fig. 2) with drusen showing a small FSL within the retinal pigment epithelium. Although the retinal pigment epithelium appears as a continuous layer in the intensity channel of a PS-SD-OCT data set (A), the DOPU image (B) clearly visualizes a small FSL (circle). The composite image (C) demonstrates the performance of the automated segmentation algorithm. Two of 11 patients with drusen had discrete FSL.

Figure 4

Comparative imaging was performed in a patient with GA (A, D, G, J). Performance of the automatic segmentation in current SD-OCT devices (A, Spectralis; D, G, Cirrus) did not delineate RPE atrophy. RPE maps derived from conventional SD-OCT data failed to identify the atrophic zones (F), which clearly conflicts with the autofluorescence image (C). Like SD–OCT, PS-SD-OCT is able to visualize the well-known morphologic features of the atrophic zone in the intensity image (J), whereas the DOPU image correctly identifies residual RPE tissue and bridges of surviving retinal pigment epithelium (L) between the atrophic lesions. The composite image (K) shows the excellent performance of the automated segmentation algorithm. To allow a comparison with the commercially available instruments (B, E), (M) shows a “conventional” PS-SD-OCT thickness map defined as distance between ILM and outer retinal border. A different form of retinal thickness maps generated from PS-SD-OCT data (N) is capable of visualizing atrophic zones (shown in gray) in a retinal thickness map. Please note the correspondence of this map (N) to the SLO (I) and the autofluorescence image (C). Intensity-based “summation maps” (H) derived from summing up reflectivity data (G) are not able to delineate the contour of the RPE reliably in this patient.

Figure 5

Typical appearance of neovascular AMD in time-domain OCT (A–C) and SD-OCT (D–F, Cirrus; G–I, Spectralis; J–L, 3D-OCT 1000). Significant differences can be found in the retinal thickness reports (C, F, I, L). These differences are often caused by segmentation errors that can be observed in representative OCT B-scans (A, D, G, J).

Figure 6

PS-OCT in nAMD (same eye as in Fig. 5). The intensity image (A) corresponds well to conventional OCT (Fig. 5). However, the DOPU image (B) clearly identifies the retinal pigment epithelium and shows circumscribed focal atrophies (white arrow) and an irregular RPE pattern. The automatic RPE segmentation algorithm follows the outline of the retinal pigment epithelium (composite image, C). The retinal thickness map shows multiple focal RPE lesions in this treatment-naive patient (D, E) in close relation to the PED. Zones of RPE atrophy are displayed as gray pixels in these two maps.

Figure 7

Characteristics of pigment epithelial lesions in nAMD. Analysis shows that 10 of 11 patients with treatment-naive nAMD had significant FSLs within the retinal pigment epithelium within the 10 central B-scans obtained by PS-SD-OCT. Seventy-three percent showed medium RPE defects (diameter, 0.2– 0.5 mm), and 18% showed large RPE defects (diameter, >0.5 mm). Most patients showed FSLs at the margins of the lesion and presented with multiple FSLs. Small peripheral RPE lesions (located outside the central 3 mm) were also present in most patients with nAMD.

Figure 8

Chorioretinal scar caused by nAMD. Residual retinal pigment epithelium cannot be differentiated from scarred structures because both appear as hyperreflective tissues in intensity-based OCT B-scans (A). PS-OCT reveals residual depolarizing tissue within the hyperreflective scar tissue complex and an irregular pattern of focal agglomerations of depolarizing structures within the scarred area that can be observed in the DOPU and the composite images (B, C). Retinal thickness maps (D, with RPE lesions in gray; E, with continuous retinal pigment epithelium and slightly differing color scale) demonstrate scattered areas of RPE atrophy (in light gray; areas with low signal intensity are displayed in dark gray). The RPE elevation map (F) reveals both RPE atrophy and focal RPE elevations.