Ophthalmic Surgery, Lasers and Imaging Retina

Clinical Science 

Widefield En Face Optical Coherence Tomography Imaging of Subretinal Drusenoid Deposits

Karen B. Schaal, MD; Andrew D. Legarreta, BA; Giovanni Gregori, PhD; John E. Legarreta, MD; Qianqian Cheng; Paul F. Stetson, PhD; Ming Cai, PhD; Michal Laron, PhD; Mary Durbin, PhD; Philip J. Rosenfeld, MD, PhD

Abstract

BACKGROUND AND OBJECTIVE:

To determine whether subretinal drusenoid deposits (SDD) can be detected on widefield en face slab images derived from spectral-domain (SD) and swept-source (SS) optical coherence tomography (OCT) volume scans.

PATIENTS AND METHODS:

Retrospective study of patients with dry age-related macular degeneration (AMD) enrolled prospectively in an OCT imaging study using SD-OCT (Cirrus HD-OCT; Carl Zeiss Meditec, Dublin, CA) with a central wavelength of 840 nm, and a prototype 100-kHz SS-OCT instrument (Carl Zeiss Meditec) with a central wavelength of 1,050 nm. Seven en face slabs were evaluated with thicknesses from 20 to 55 µm and positioned at distances up to 55 µm above the retinal pigment epithelium (RPE). A montage of 6 × 6 mm SD-OCT en face images of the posterior pole from each patient was compared with a 9 × 12 mm SS-OCT single en face slab image and with color, autofluorescence, and infrared reflectance images.

RESULTS:

A total of 160 patients (256 eyes) underwent scanning with both OCT instruments; 57 patients (95 eyes) also underwent multimodal fundus imaging. Of 95 eyes, 32 (34%) were diagnosed with reticular pseudodrusen (RPD) using multimodal imaging. All eyes with RPD demonstrated a pattern of SDD on widefield en face OCT similar to that observed for RPD. The en face slab image that consistently identified SDD was the 20-µm thick slab with boundaries from 35 to 55 µm above the RPE.

CONCLUSION:

Widefield en face slab imaging with SD-OCT and SS-OCT can detect SDD and could replace multimodal imaging for the diagnosis of RPD in the future.

[Ophthalmic Surg Lasers Imaging Retina. 2015;46:550–559.]

From the Bascom Palmer Eye Institute (KBS, ADL, GG, JEL, QC, PJR), University of Miami Miller School of Medicine, Miami, Florida; and the Department of Research and Development (PFS, MC, ML, MD), Carl Zeiss Meditec, Dublin, California.

Supported by a grant from Carl Zeiss Meditec, the Macula Vision Research Foundation, core grant P30EY014801 from the National Eye Institute Center, an unrestricted grant from the Research to Prevent Blindness, the Feig Family Foundation, and the Emma Clyde Hodge Memorial Foundation.

Dr. Schaal received funding from the German Research Foundation (DFG). Dr. Gregori received research support from Carl Zeiss Meditec and co-owns a patent that is licensed to Carl Zeiss Meditec. Dr. Rosenfeld received research support from Carl Zeiss Meditec, Acucela, Advanced Cell Technology, and GlaxoSmithKline and is a consultant for Acucela, Alcon, Bayer, Boehringer Ingelheim, Chengdu Kanghong Biotech, Genentech, Healios K.K., Merck, Oraya, Roche, Sanofi/Genzyme, and Xcovery Vision. Drs. Stetson, Cai, Laron, and Durbin are employees of Carl Zeiss Meditec. The remaining authors report no relevant financial disclosures.

The authors thank the patients who participated in the study, Sandra O’Mellan who acquired the optical coherence tomography scans, and the photographers who assisted in acquiring the multimodal images.

Address correspondence to Philip J. Rosenfeld, MD, PhD, Bascom Palmer Eye Institute, 900 NW 17th Street, Miami, FL 33136; email: prosenfeld@med.miami.edu.

Received: December 04, 2014
Accepted: March 13, 2015

Abstract

BACKGROUND AND OBJECTIVE:

To determine whether subretinal drusenoid deposits (SDD) can be detected on widefield en face slab images derived from spectral-domain (SD) and swept-source (SS) optical coherence tomography (OCT) volume scans.

PATIENTS AND METHODS:

Retrospective study of patients with dry age-related macular degeneration (AMD) enrolled prospectively in an OCT imaging study using SD-OCT (Cirrus HD-OCT; Carl Zeiss Meditec, Dublin, CA) with a central wavelength of 840 nm, and a prototype 100-kHz SS-OCT instrument (Carl Zeiss Meditec) with a central wavelength of 1,050 nm. Seven en face slabs were evaluated with thicknesses from 20 to 55 µm and positioned at distances up to 55 µm above the retinal pigment epithelium (RPE). A montage of 6 × 6 mm SD-OCT en face images of the posterior pole from each patient was compared with a 9 × 12 mm SS-OCT single en face slab image and with color, autofluorescence, and infrared reflectance images.

RESULTS:

A total of 160 patients (256 eyes) underwent scanning with both OCT instruments; 57 patients (95 eyes) also underwent multimodal fundus imaging. Of 95 eyes, 32 (34%) were diagnosed with reticular pseudodrusen (RPD) using multimodal imaging. All eyes with RPD demonstrated a pattern of SDD on widefield en face OCT similar to that observed for RPD. The en face slab image that consistently identified SDD was the 20-µm thick slab with boundaries from 35 to 55 µm above the RPE.

CONCLUSION:

Widefield en face slab imaging with SD-OCT and SS-OCT can detect SDD and could replace multimodal imaging for the diagnosis of RPD in the future.

[Ophthalmic Surg Lasers Imaging Retina. 2015;46:550–559.]

From the Bascom Palmer Eye Institute (KBS, ADL, GG, JEL, QC, PJR), University of Miami Miller School of Medicine, Miami, Florida; and the Department of Research and Development (PFS, MC, ML, MD), Carl Zeiss Meditec, Dublin, California.

Supported by a grant from Carl Zeiss Meditec, the Macula Vision Research Foundation, core grant P30EY014801 from the National Eye Institute Center, an unrestricted grant from the Research to Prevent Blindness, the Feig Family Foundation, and the Emma Clyde Hodge Memorial Foundation.

Dr. Schaal received funding from the German Research Foundation (DFG). Dr. Gregori received research support from Carl Zeiss Meditec and co-owns a patent that is licensed to Carl Zeiss Meditec. Dr. Rosenfeld received research support from Carl Zeiss Meditec, Acucela, Advanced Cell Technology, and GlaxoSmithKline and is a consultant for Acucela, Alcon, Bayer, Boehringer Ingelheim, Chengdu Kanghong Biotech, Genentech, Healios K.K., Merck, Oraya, Roche, Sanofi/Genzyme, and Xcovery Vision. Drs. Stetson, Cai, Laron, and Durbin are employees of Carl Zeiss Meditec. The remaining authors report no relevant financial disclosures.

The authors thank the patients who participated in the study, Sandra O’Mellan who acquired the optical coherence tomography scans, and the photographers who assisted in acquiring the multimodal images.

Address correspondence to Philip J. Rosenfeld, MD, PhD, Bascom Palmer Eye Institute, 900 NW 17th Street, Miami, FL 33136; email: prosenfeld@med.miami.edu.

Received: December 04, 2014
Accepted: March 13, 2015

Introduction

The presence of reticular pseudodrusen (RPD) has been associated with decreased photoreceptor sensitivity1 and the onset of late age-related macular degeneration (AMD),2–12 as well as an increased risk of AMD progression in the fellow eye.4,13 RPD are considered the clinical manifestation of subretinal drusenoid deposits (SDD),8,14 which have been identified histopathologically,8,15 and can be identified by spectral-domain optical coherence tomography (SD-OCT).12,15–18 SDD are considered to be dynamic structures10,17 and are classified by an OCT staging system that depends on their size and impact on the overlying photoreceptors.15,17 RPD and SDD have been associated with a thin choroid,19–22 and the disappearance of RPD and regression of SDD have been associated with outer retinal atrophy in the absence of typical late AMD findings such as geographic atrophy (GA), which suggests that this might represent a distinct form of late AMD.23

Multimodal imaging can be used to classify RPD and SDD based on their appearance using fundus autofluorescence (FAF), infrared reflectance (IR), color fundus, and SD-OCT imaging.3,9,15,18,24,25 Given the importance of cross-sectional anatomy26 in diagnosing SDD, SD-OCT imaging has become the preferred strategy for their diagnosis.27 Historically, the diagnosis of RPD has required camera-based multispectral imaging, but more recently, multispectral confocal scanning laser ophthalmoscopy (cSLO) en face imaging has gained prominence.16,28 The advantage of multispectral en face fundus imaging is its ability to capture a widefield image of the fundus to visualize RPD. However, the disadvantages of widefield multispectral en face fundus imaging include time-consuming examinations and the bright flashes, which are uncomfortable for patients. In addition, cSLO systems are expensive, and the bright blue (488 nm) excitation light for acquisition of the FAF image is particularly uncomfortable for patients. Moreover, the presence of a cataract, which occurs frequently in elderly AMD patients, limits the acquisition of good quality autofluorescence images, which can interfere with the detection of RPD.1,2,6,7,9–11,15,23,24,26,29–33

Although OCT provides the best imaging strategy to identify SDD, the technique has been used primarily to scan the central macula and requires operator expertise to redirect the scans to where RPD are often located, such as above the superior and inferior arcades, and nasal to the optic nerve. However, widefield en face OCT imaging provides a useful strategy for visualizing SDD and should provide advantages over typical multimodal imaging, including rapid acquisition of both en face and cross-sectional images from a single volume scan through an undilated pupil as well as better imaging through cataracts. The purpose of this study was to demonstrate the ability to detect SDD using widefield en face SD-OCT and swept-source OCT (SS-OCT) imaging of patients with RPD. The pattern of SDD visualized with en face OCT imaging was compared with the distribution of RPD identified using traditional color, IR, and FAF imaging.

Patients and Methods

Patients were recruited from the outpatient clinic at the Bascom Palmer Eye Institute. Approval for the collection and analysis of SD-OCT images was obtained from the institutional review board at the University of Miami Miller School of Medicine, and all of the participants signed informed research consent forms. The study was performed in accordance with Health Insurance Portability and Accountability Act of 1996 regulations.

Between August 2013 and August 2014, patients with the diagnosis of nonexudative (dry) AMD were included in this retrospective study; the imaging data were collected prospectively as part of the approved ongoing study. Patients had to meet the criteria of same-day imaging with an SD-OCT instrument (Cirrus HD-OCT; Carl Zeiss Meditec, Dublin, CA), having a central wavelength of 840 nm, and a prototype Zeiss 100-kHz SS-OCT instrument (Carl Zeiss Meditec), having a central wavelength of 1050 ± 50 nm. In a subset of patients, multimodal imaging, including color, IR reflectance, and FAF imaging, was performed. Color fundus imaging was obtained using a fundus camera-based flash system (TRC-50DX; Topcon Medical Systems, Oakland, NJ), infrared reflectance imaging was acquired with a cSLO system (Spectralis; Heidelberg Engineering, Heidelberg, Germany; IR λ: 820 nm), and FAF imaging was acquired with either the Spectralis cSLO system (excitation λ: 488 nm; detection λ: > 500 nm) or a Topcon system (excitation λ: 535 to 585 nm; detection λ: 605 to 715 nm). Patients with RPD then were identified based on color, IR, and FAF imaging. Two of the authors (KBS and PJR) reviewed the images and reached a consensus diagnosis of RPD prior to the review of any OCT images.

SD-OCT Scanning Protocol and Data Processing

The SD-OCT images were acquired by scanning each eye six times in a single session to obtain six different overlapping retinal locations centered on the fovea, the superior and inferior arcade in the central macula, the region just temporal to the fovea, the optic disc, and the area just nasal to the optic disc. Each scan covered a retinal area of 6 × 6 mm. A raster scan protocol (200 × 200 A-scans) was used and resulted in the acquisition of an SD-OCT dataset at a scanning rate of 27,000 A-scans per second consisting of 40,000 uniformly spaced A-scans, with each raster array organized as 200 horizontal B-scans, and each B-scan consisting of 200 A-scans.

For each of the six SD-OCT volume scans, seven different slabs were generated manually using the commercially available review software by adjusting the inner and outer boundaries of a slab as described previously.34 The slab followed the segmentation of the retinal pigment epithelium (RPE). The inner and outer distances of the boundaries above the RPE are given by the first and second values, with the thickness of the slab represented by the difference between the two values. The following slabs were investigated: 0 to 40, 10 to 40, 0 to 55, 10 to 55, 20 to 40, 20 to 55, and 35 to 55 µm. The seven en face slab composite images were generated from the six volume scans obtained at each of the different retinal positions by generating the appropriate slabs from each volume scan and then overlapping and aligning the slabs by using the retinal vasculature as landmarks to create a composite image (Figures 2, 5, and 8).

Spectral-domain OCT en face composite images of a normal right eye in a 57-year-old man. The en face images correspond to the slabs shown in Figure 1. (A) Composite full-thickness OCT fundus images. (B) Composite of 40 µm thick slabs, located 0 to 40 µm above the retinal pigment epithelium (RPE). (C) Composite of 55 µm thick slabs, located 0 to 55 µm above the RPE. (D) Composite of 30 µm thick slabs, located 10 to 40 µm above the RPE. (E) Composite of 45 µm thick slabs, located 10 to 55 µm above the RPE. (F) Composite of 20 µm thick slabs, located 20 to 40 µm above the RPE. (G) Composite of 35 µm thick slabs, located 20 to 55 µm above the RPE. (H) Composite of 20 µm thick slabs, located 35 to 55 µm above the RPE.

Figure 2.

Spectral-domain OCT en face composite images of a normal right eye in a 57-year-old man. The en face images correspond to the slabs shown in Figure 1. (A) Composite full-thickness OCT fundus images. (B) Composite of 40 µm thick slabs, located 0 to 40 µm above the retinal pigment epithelium (RPE). (C) Composite of 55 µm thick slabs, located 0 to 55 µm above the RPE. (D) Composite of 30 µm thick slabs, located 10 to 40 µm above the RPE. (E) Composite of 45 µm thick slabs, located 10 to 55 µm above the RPE. (F) Composite of 20 µm thick slabs, located 20 to 40 µm above the RPE. (G) Composite of 35 µm thick slabs, located 20 to 55 µm above the RPE. (H) Composite of 20 µm thick slabs, located 35 to 55 µm above the RPE.

Spectral-domain OCT composites of the posterior pole of the right eye in a 70-year-old woman with reticular pseudodrusen (RPD), showing different en face slabs, which show a varying RPD pattern depending on the intraretinal location of the slab. (A) Composite (full-thickness) OCT fundus images. (B) Composite of 40-µm thick slabs, located 0 to 40 µm above the retinal pigment epithelium (RPE). (C) Composite of 55-µm thick slabs, located 0 to 55 µm above the RPE. (D) Composite of 30-µm thick slabs, located 10 to 40 µm above the RPE. (E) Composite of 45-µm thick slabs, located 10 to 55 µm above the RPE. (F) Composite of 20-µm thick slabs, located 20 to 40 µm above the RPE. (G) Composite of 35-µm thick slabs, located 20 to 55 µm above the RPE. (H) Composite of 20-µm thick slabs, located 35 to 55 µm above the RPE, which shows the RPD pattern most apparently.

Figure 5.

Spectral-domain OCT composites of the posterior pole of the right eye in a 70-year-old woman with reticular pseudodrusen (RPD), showing different en face slabs, which show a varying RPD pattern depending on the intraretinal location of the slab. (A) Composite (full-thickness) OCT fundus images. (B) Composite of 40-µm thick slabs, located 0 to 40 µm above the retinal pigment epithelium (RPE). (C) Composite of 55-µm thick slabs, located 0 to 55 µm above the RPE. (D) Composite of 30-µm thick slabs, located 10 to 40 µm above the RPE. (E) Composite of 45-µm thick slabs, located 10 to 55 µm above the RPE. (F) Composite of 20-µm thick slabs, located 20 to 40 µm above the RPE. (G) Composite of 35-µm thick slabs, located 20 to 55 µm above the RPE. (H) Composite of 20-µm thick slabs, located 35 to 55 µm above the RPE, which shows the RPD pattern most apparently.

Spectral-domain OCT en face composite slabs of the right eye in a 75-year-old man with a dense cataract and reticular pseudodrusen (RPD) showing varying pseudodrusen patterns depending on the intraretinal location of the slab. Image quality is not limited despite the presence of a dense cataract. (A) Composite of (full-thickness) OCT fundus images. (B) Composite of 40 µm thick slabs, located 0 to 40 µm above the retinal pigment epithelium (RPE). (C) Composite of 55 µm thick slabs, located 0 to 55 µm above the RPE. (D) Composite of 30 µm thick slabs, located 10 to 40 µm above the RPE. (E) Composite of 45 µm thick slabs, located 10 to 55 µm above the RPE. (F) Composite of 20 µm thick slabs, located 20 to 40 µm above the RPE. (G) Composite of 35 µm thick slabs, located 20 to 55 µm above the RPE. (H) Composite of 20 µm thick slabs located 35 to 55 µm above the RPE, corresponding well to the RPD pattern seen on multimodal imaging.

Figure 8.

Spectral-domain OCT en face composite slabs of the right eye in a 75-year-old man with a dense cataract and reticular pseudodrusen (RPD) showing varying pseudodrusen patterns depending on the intraretinal location of the slab. Image quality is not limited despite the presence of a dense cataract. (A) Composite of (full-thickness) OCT fundus images. (B) Composite of 40 µm thick slabs, located 0 to 40 µm above the retinal pigment epithelium (RPE). (C) Composite of 55 µm thick slabs, located 0 to 55 µm above the RPE. (D) Composite of 30 µm thick slabs, located 10 to 40 µm above the RPE. (E) Composite of 45 µm thick slabs, located 10 to 55 µm above the RPE. (F) Composite of 20 µm thick slabs, located 20 to 40 µm above the RPE. (G) Composite of 35 µm thick slabs, located 20 to 55 µm above the RPE. (H) Composite of 20 µm thick slabs located 35 to 55 µm above the RPE, corresponding well to the RPD pattern seen on multimodal imaging.

Prototype SS-OCT Widefield Scanning Protocol and Data Processing

The SS-OCT widefield images were acquired using a modified Cirrus device with a swept-source laser prototype with a central wavelength of 1,050 nm (1,000 to 1,100 nm full width) and a scanning speed of 100,000 A-scans per second (100 kHz). This device has a lateral resolution of 20 µm and an axial resolution of 5 µm. A raster scan protocol (512 × 512 macular cube) consisted of 512 A-scans per B-scan and 512 B-scans per volume over an area of 9 × 12 mm. The raw datasets were exported and sent to Zeiss for further processing. A prototype segmentation algorithm was applied to identify the RPE, and the same seven slab configurations were generated (0 to 40, 10 to 40, 0 to 55, 10 to 55, 20 to 40, 20 to 55, and 35 to 55 µm above the RPE segmentation surface). En face images then were generated from these slabs.

Results

Figure 1 shows SD-OCT B-scans from a normal control eye with the boundaries for all seven slabs superimposed on the B-scans. The slabs differ based on their location above the RPE and their thickness. In each image, the slab position and thickness is shown in the lower right corner of the panel. The first number represents the position of the outer slab boundary in relation to the RPE, and the second number represents the position of the inner slab boundary in its relation to the RPE. The difference between the two numbers represents the thickness of the slab. Figure 2 shows the en face SD-OCT composites, which were assembled from the slabs derived from the boundary positions shown in Figure 1. Figure 3 demonstrates the same seven en face slab images from the same normal control eye, but these images were extracted from the widefield SS-OCT volume scans. The different en face slab images show no obvious pathology. Of note, the en face slab images with an inner border of 55 µm above the RPE appear to have a darker appearance. Figures 2A and 3A represent full-thickness en face fundus images using the SD-OCT and SS-OCT volume scans, respectively.

Spectral-domain OCT B-scans through the foveal center of a normal retina in the right eye of a 57-year-old man. The blue lines indicate the position of the intraretinal slabs, superimposed on a B-scan. (A) B-scan with no overlay to demonstrate the retinal layers. (B) B-scan showing a 40-µm thick slab overlay located 0 to 40 µm above the retinal pigment epithelium (RPE). (C) B-scan showing a 55-µm thick slab overlay located 0 to 55 µm above the RPE. (D) B-scan showing a 30-µm thick slab overlay located 10 to 40 µm above the RPE. (E) B-scan showing a 45-µm thick slab overlay located 10 to 55 µm above the RPE. (F) B-scan showing a 20-µm thick slab overlay located 20 to 40 µm above the RPE. (G) B-scan showing a 35-µm thick slab overlay located 20 to 55 µm above the RPE. (H) B-scan showing a 20-µm thick slab overlay located 35 to 55 µm above the RPE.

Figure 1.

Spectral-domain OCT B-scans through the foveal center of a normal retina in the right eye of a 57-year-old man. The blue lines indicate the position of the intraretinal slabs, superimposed on a B-scan. (A) B-scan with no overlay to demonstrate the retinal layers. (B) B-scan showing a 40-µm thick slab overlay located 0 to 40 µm above the retinal pigment epithelium (RPE). (C) B-scan showing a 55-µm thick slab overlay located 0 to 55 µm above the RPE. (D) B-scan showing a 30-µm thick slab overlay located 10 to 40 µm above the RPE. (E) B-scan showing a 45-µm thick slab overlay located 10 to 55 µm above the RPE. (F) B-scan showing a 20-µm thick slab overlay located 20 to 40 µm above the RPE. (G) B-scan showing a 35-µm thick slab overlay located 20 to 55 µm above the RPE. (H) B-scan showing a 20-µm thick slab overlay located 35 to 55 µm above the RPE.

Swept-source OCT widefield en face images (9 × 12 mm) showing different intraretinal slabs of a normal right eye in a 57-year-old man. The en face images correspond to the slabs shown in Figures 1 and 2. (A) Full-thickness OCT fundus images. (B) Widefield en face image of a 40-µm thick slab, located 0 to 40 µm above the retinal pigment epithelium (RPE). (C) Widefield en face image of a 55 µm thick slab, located 0 to 55 µm above the RPE. (D) Widefield en face image of a 30 µm thick slab, located 10 to 40 µm above the RPE. (E) Widefield en face image of a 45 µm thick slab, located 10 to 55 µm above the RPE. (F) Widefield en face image of a 20 µm thick slab, located 20 to 40 µm above the RPE. (G) Widefield en face of a 35 µm thick slab, located 20 to 55 µm above the RPE. (H) Widefield en face image of a 20 µm thick slab, located 35 to 55 µm above the RPE.

Figure 3.

Swept-source OCT widefield en face images (9 × 12 mm) showing different intraretinal slabs of a normal right eye in a 57-year-old man. The en face images correspond to the slabs shown in Figures 1 and 2. (A) Full-thickness OCT fundus images. (B) Widefield en face image of a 40-µm thick slab, located 0 to 40 µm above the retinal pigment epithelium (RPE). (C) Widefield en face image of a 55 µm thick slab, located 0 to 55 µm above the RPE. (D) Widefield en face image of a 30 µm thick slab, located 10 to 40 µm above the RPE. (E) Widefield en face image of a 45 µm thick slab, located 10 to 55 µm above the RPE. (F) Widefield en face image of a 20 µm thick slab, located 20 to 40 µm above the RPE. (G) Widefield en face of a 35 µm thick slab, located 20 to 55 µm above the RPE. (H) Widefield en face image of a 20 µm thick slab, located 35 to 55 µm above the RPE.

A total of 160 patients (256 eyes) were scanned with both OCT instruments, and 57 patients (95 eyes) also underwent multimodal fundus imaging. Of the 95 eyes, 32 (34%) were diagnosed with RPD using multimodal imaging, and all of these eyes demonstrated a characteristic SDD pattern on widefield en face OCT. After comparing the different slabs with the multimodal images (color, FAF, and IR images), we found the SDD pattern on the widefield 35 to 55 µm slab en face image was reproducibly characteristic of the RPD pattern seen on multimodal imaging. As an example, Figure 4 demonstrates multimodal images and the SD-OCT cross-sectional B-scan of a patient with SDD. Figures 5 and 6 show the seven different widefield en face SD-OCT and SS-OCT slabs, which reveal the characteristic SDD pattern in all of the slabs, but the pattern is most apparent on the 35 to 55 µm slab.

Images of the right eye in a 70-year-old woman with reticular pseudodrusen (RPD), discrete areas of perifoveal focal scarring, and a few typical drusen (OD). (A) Color fundus image of the posterior pole showing the pattern of RPD located superotemporal and superior to the fovea. (B) Topcon fundus auto-fluorescence (FAF) image showing the pattern of RPD. (C) Infrared reflectance (IR) and confocal scanning laser ophthalmoscopic image (cSLO) of the posterior pole, showing the RPD pattern in the macular region. The horizontal green line indicates the position of the corresponding spectral-domain OCT B-scan. (D) Spectral-domain OCT B-scan through the macula demonstrating typical drusen (central part of the scan), as well as multiple accumulations of subretinal drusenoid deposits (SDD), leading to an undulating appearance of the overlaying inner segment/outer segment band (SDD stage 2).

Figure 4.

Images of the right eye in a 70-year-old woman with reticular pseudodrusen (RPD), discrete areas of perifoveal focal scarring, and a few typical drusen (OD). (A) Color fundus image of the posterior pole showing the pattern of RPD located superotemporal and superior to the fovea. (B) Topcon fundus auto-fluorescence (FAF) image showing the pattern of RPD. (C) Infrared reflectance (IR) and confocal scanning laser ophthalmoscopic image (cSLO) of the posterior pole, showing the RPD pattern in the macular region. The horizontal green line indicates the position of the corresponding spectral-domain OCT B-scan. (D) Spectral-domain OCT B-scan through the macula demonstrating typical drusen (central part of the scan), as well as multiple accumulations of subretinal drusenoid deposits (SDD), leading to an undulating appearance of the overlaying inner segment/outer segment band (SDD stage 2).

Swept-source SS-OCT widefield en face images (9 × 12 mm) showing different intraretinal slabs of the right eye in a 70-year-old woman with reticular pseudodrusen (RPD). The RPD patterns vary depending on the intraretinal location of the slab. (A) Full-thickness OCT fundus images. (B) Widefield en face image of a 40 µm thick slab, located 0 to 40 µm above the retinal pigment epithelium (RPE). (C) Widefield en face image of a 55 µm thick slab, located 0 to 55 µm above the RPE. (D) Widefield en face image of a 30 µm thick slab, located 10 to 40 µm above the RPE. (E) Widefield en face image of a 45 µm thick slab, located 10 to 55 µm above the RPE. (F) Widefield en face image of a 20 µm thick slab, located 20 to 40 µm above the RPE. (G) Widefield en face image of a 35 µm thick slab, located 20 to 55 µm above the RPE. (H) Widefield en face image of a 20 µm thick slab, located 35 to 55 µm above the RPE, corresponding well to the RPD pattern seen on multimodal imaging.

Figure 6.

Swept-source SS-OCT widefield en face images (9 × 12 mm) showing different intraretinal slabs of the right eye in a 70-year-old woman with reticular pseudodrusen (RPD). The RPD patterns vary depending on the intraretinal location of the slab. (A) Full-thickness OCT fundus images. (B) Widefield en face image of a 40 µm thick slab, located 0 to 40 µm above the retinal pigment epithelium (RPE). (C) Widefield en face image of a 55 µm thick slab, located 0 to 55 µm above the RPE. (D) Widefield en face image of a 30 µm thick slab, located 10 to 40 µm above the RPE. (E) Widefield en face image of a 45 µm thick slab, located 10 to 55 µm above the RPE. (F) Widefield en face image of a 20 µm thick slab, located 20 to 40 µm above the RPE. (G) Widefield en face image of a 35 µm thick slab, located 20 to 55 µm above the RPE. (H) Widefield en face image of a 20 µm thick slab, located 35 to 55 µm above the RPE, corresponding well to the RPD pattern seen on multimodal imaging.

To demonstrate the improved imaging of OCT through cataract compared with multimodal imaging, we examined a patient with poor multimodal imaging (Figure 7) who underwent SD-OCT imaging. This patient was not in the main dataset because he was scanned with the SD-OCT device before the prototype SS-OCT was available at our center. The compromised image quality due to the media opacity is evident, which impeded the diagnosis of SDD. Figure 8 shows the en face SD-OCT composite slabs from the patient with the cataract, and due to the longer wavelength used with the SD-OCT technique (840 nm), the cataract had little if any impact on image quality, and the SDD were easily identified.

Images of the right eye in a 75-year-old man with reticular pseudodrusen (RPD), typical drusen, and a dense cataract, which accounts for the limited multimodal image quality. (A) Color fundus image of the posterior pole showing multiple circumscribed drusen in the macular region. An RPD pattern cannot be seen due to the poor image quality caused by cataract. (B) Fundus autofluorescence (FAF) image (Heidelberg Engineering) showing the RPD pattern in the macular region. (C) Infrared reflectance (IR) confocal scanning laser ophthalmoscopy image showing the RPD pattern, as well as a central hyperreflective pattern, corresponding to conventional drusen. The horizontal green line indicates the position of the corresponding cross-sectional spectral-domain OCT B-scan (D). (D) Cross-sectional SD-OCT B-scan through the macula demonstrating multiple accumulations of subretinal drusenoid deposits (SDD), which have a spike-like appearance (SDD stage 3) and disrupt the inner segment/outer segment band.

Figure 7.

Images of the right eye in a 75-year-old man with reticular pseudodrusen (RPD), typical drusen, and a dense cataract, which accounts for the limited multimodal image quality. (A) Color fundus image of the posterior pole showing multiple circumscribed drusen in the macular region. An RPD pattern cannot be seen due to the poor image quality caused by cataract. (B) Fundus autofluorescence (FAF) image (Heidelberg Engineering) showing the RPD pattern in the macular region. (C) Infrared reflectance (IR) confocal scanning laser ophthalmoscopy image showing the RPD pattern, as well as a central hyperreflective pattern, corresponding to conventional drusen. The horizontal green line indicates the position of the corresponding cross-sectional spectral-domain OCT B-scan (D). (D) Cross-sectional SD-OCT B-scan through the macula demonstrating multiple accumulations of subretinal drusenoid deposits (SDD), which have a spike-like appearance (SDD stage 3) and disrupt the inner segment/outer segment band.

Discussion

SD-OCT and SS-OCT widefield en face slab images identified the location of SDD and demonstrated the utility of widefield OCT imaging for the detection of RPD. The patterns of RPD and SDD were detected reproducibly with an en face slab located 35 to 55 µm above the RPE. The advantages of using the OCT devices are that the imaging times are shorter and the wavelength used for scanning (840 nm for SD-OCT and 1050 nm for SS-OCT) is more comfortable than the shorter wavelengths and bright flashes needed for FAF, IR, and color imaging.5,13,14,18,26,27,35,36 In addition, OCT imaging of SDD can be performed through an undilated pupil, and good quality SD-OCT images can be obtained even in the presence of cataract (Figure 8). Moreover, the longer wavelength of SS-OCT imaging compared with SD-OCT imaging should be affected even less by the presence of a cataract.

Although composite images using multiple overlapping SD-OCT volume scans can be constructed to provide widefield images, this strategy requires significant patient cooperation, an experienced imaging technician, and postprocessing time to generate the composite. A clear advantage of the SS-OCT device is the short image acquisition time (less than 4 seconds) and the creation of a widefield 9 × 12 mm en face image from a single volume scan (Figures 3 and 6).

The selection of the seven slabs used in this comparative study were chosen empirically based on knowing the location of SDD in the subretinal space internal to the RPE.8,15,28,33,37 For this reason, we chose slabs spanning the distance from the RPE to 55 µm above the RPE. Due to the hyper-reflective bands generated by the RPE and the interdigitation between the RPE and the photoreceptor outer segment tips, we found that the SDD pattern could not be clearly seen using the 0 to 40 µm slab (Figures 5B, 6B, and 8B). Therefore, the outer slab boundary was moved from 0 µm (RPE level) to 10 µm above the RPE with the assumption that the SDD could still be visualized without the interference from bands three and four. An upper slab boundary of 40 µm was selected because a previous study by Nunes et al34 demonstrated that the 20 to 40 µm slab showed whether the inner segment/outer segment (IS/OS) band was intact and whether changes in this slab correlated with the progression of geographic atrophy in some AMD patients. However, the 20 to 40 µm slab did not appear to be the best at visualizing the SDD. By moving the outer slab boundary further away from the hyperreflective signal associated with the RPE, we were able to incorporate the more hyporeflective signal from the outer nuclear layer, which darkened the overall en face image (Figures 5H, 6H, and 8H). When put to the test and the seven different slabs were compared, we found that the 35 to 55 µm slab showed the SDD pattern most unambiguously. In 2011, Switzer et al38 demonstrated a similar pattern to our findings when manually segmenting SD-OCT C-scans, but the exact location and thickness of the slabs were not mentioned. In a more recent study, limited en face imaging was used to show that RPD and SDD colocalize and most likely represent the same structures.39

En face SD-OCT imaging has been used in other retinal diseases such as multiple evanescent white dot syndrome and macular telangiectasia type 2,40–42 whereas en face SS-OCT imaging has been used in eyes with a branch retinal vein occlusion to demonstrate thinning of inner retinal layers as an indicator of capillary nonperfusion.43 In addition, an SS-OCT prototype (Topcon) was used for imaging the macular choroidal thickness and volume in patients with reticular pseudodrusen,22 but this strategy was not used to image the SDD pattern.

Why SDD leads to a certain pattern on multimodal imaging has been a question of great interest,18,24,28 and depending on their appearance and height on SD-OCT, SDD can be classified into different stages.15,17 A central target appearance (central hyperreflectivity surrounded by a hyporeflective ring) often is seen with cSLO imaging.18 Based on a theory by Querques et al,18 the target appearance can be recognized after the SDD has reached a certain height and has broken through the IS/OS boundary. Alten et al28 hypothesized that the hyporeflective annulus might consist of deflected photoreceptors, whereas the isoreflective center consists of unphagocytosed photoreceptor outer segments. Using adaptive optics imaging, Mrejen et al44 showed reduced visibility of cones overlying SDD, which could result from a change in their orientation, an alteration of their cellular architecture, or the absence of the cones themselves. A distinct en face annular structure of stage 3 SDD also was revealed in an adaptive optics scanning laser ophthalmoscopy study37,45 in which stage 3 SDD appeared as a distinct hyporeflective annulus surrounding a reflective core, which was thought to consist of SDD material itself and not the photoreceptors.37

Figure 7D shows stage 3 SDD according to the classification system introduced by Zweifel et al15 and the corresponding 35 to 55 µm en face OCT image (Figure 8H) shows hyperreflective dots, whereas Figure 4D shows stage 2 SDD and the corresponding 35 to 55 µm en face OCT images (Figures 5H and 6H) show a more interlaced hyperreflective pattern. In the latter case, we hypothesized that the hyperreflective IS/OS band is “elevated” by early stage SDD into the 35 to 55 µm slab, and the hyperreflective pattern (Figures 5H and 6H) is not caused by the SDD themselves, but by portions of the IS/OS band overlying the SDD being elevated by the SDD into the slab. The hyperreflective dots in Figure 8H could be caused by the SDD themselves, reaching into the hyporeflective outer nuclear layer and having broken through the IS/OS band, as seen on the cross-sectional SD-OCT B-scan in Figure 7D. Although histopathological studies have identified refractile material on the upper surface of the deposits,15 their impact on OCT visualization has yet to be determined.

Limitations of this study include the recruitment of only stage 2 and 3 SDD cases in our clinic population. We have not identified patients with early SDD (stage 1) and may have failed to identify late SDD (stage 4) in which the SDD have regressed leaving outer retinal atrophy. It will be of interest to follow these cases and assess the progression of SDD using widefield en face OCT imaging. Furthermore, although we reviewed the color, FAF, and IR images in a masked fashion to diagnose RPD without knowing the OCT outcomes, we have not yet reviewed all of the widefield OCT images in a masked fashion to determine the sensitivity and specificity of OCT imaging for identifying all cases of RPD. This study is ongoing.

In conclusion, we demonstrated the utility of widefield en face SD-OCT and SS-OCT imaging to detect SDD with a pattern corresponding to RPD seen on multispectral multimodal imaging. We found that the 35 to 55 µm slab was best at showing the characteristic RPD pattern. Although multimodal imaging is the gold standard, OCT imaging is faster, more comfortable for the patient, and more cost effective. The question of SD-OCT or SS-OCT imaging alone being equal to or superior to multimodal imaging in diagnosing RPD needs to be addressed in future studies and was not the purpose of the current study. This study is the first report of using a single, fast, and cost-effective imaging modality for the detection of RPD. Although there are certain advantages of using widefield en face SD-OCT and SS-OCT imaging, future studies will determine whether this strategy alone can unambiguously diagnose the pattern of SDD in eyes with RPD.

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