Faculty Bibliography

PURPOSE: To describe the features of intraretinal retinal pigment epithelium (RPE) migration documented on a prototype spectral-domain, high-speed, ultrahigh-resolution optical coherence tomography (OCT) device in a group of patients with early to intermediate dry age-related macular degeneration (AMD) and to correlate intraretinal RPE migration on OCT to RPE pigment clumping on fundus photographs. DESIGN: Retrospective, noncomparative, noninterventional case series. PARTICIPANTS: Fifty-five eyes of 44 patients seen at the New England Eye Center between December 2007 and June 2008 with early to intermediate dry AMD. METHODS: Three-dimensional OCT scan sets from all patients were analyzed for the presence of intraretinal RPE migration, defined as small discreet hyperreflective and highly backscattering lesions within the neurosensory retina. Fundus photographs also were analyzed to determine the presence of RPE pigment clumping, defined as black, often spiculated, areas of pigment clumping within the macula. The en face OCT images were correlated with fundus photographs to demonstrate correspondence of intraretinal RPE migration on OCT and RPE clumping on fundus photography. MAIN OUTCOME MEASURES: Drusen, dry AMD, intraretinal RPE migration, and RPE pigment clumping. RESULTS: On OCT scans, 54.5% of eyes (61.4% of patients) demonstrated intraretinal RPE migration. Of the fundus photographs, 56.4% demonstrated RPE pigment clumping. All eyes with intraretinal RPE migration on OCT had corresponding RPE pigment clumping on fundus photographs. The RPE pigment migrated most frequently into the outer nuclear layer (66.7% of eyes) and less frequently into more anterior retinal layers. Intraretinal RPE migration mainly occurred above areas of drusen (73.3% of eyes). CONCLUSIONS: The appearance of intraretinal RPE migration on OCT is a common occurrence in early to intermediate dry AMD, occurring in 54.5% of eyes, or 61.4% of patients. The area of intraretinal RPE migration on OCT always correlated to areas of pigment clumping on fundus photography. Conversely, all but 1 eye with RPE pigment clumping on fundus photography also had areas of intraretinal RPE migration on OCT. The high incidence of intraretinal RPE migration observed above areas of drusen suggests that drusen may play physical and catalytic roles in facilitating intraretinal RPE migration in dry AMD patients.

PURPOSE: To develop an automated method to identify the normal macula and three macular pathologies (macular hole [MH], macular edema [ME], and age-related macular degeneration [AMD]) from the fovea-centered cross sections in three-dimensional (3D) spectral-domain optical coherence tomography (SD-OCT) images. METHODS: A sample of SD-OCT macular scans (macular cube 200 x 200 or 512 x 128 scan protocol; Cirrus HD-OCT; Carl Zeiss Meditec, Inc., Dublin, CA) was obtained from healthy subjects and subjects with MH, ME, and/or AMD (dataset for development: 326 scans from 136 subjects [193 eyes], and dataset for testing: 131 scans from 37 subjects [58 eyes]). A fovea-centered cross-sectional slice for each of the SD-OCT images was encoded using spatially distributed multiscale texture and shape features. Three ophthalmologists labeled each fovea-centered slice independently, and the majority opinion for each pathology was used as the ground truth. Machine learning algorithms were used to identify the discriminative features automatically. Two-class support vector machine classifiers were trained to identify the presence of normal macula and each of the three pathologies separately. The area under the receiver operating characteristic curve (AUC) was calculated to assess the performance. RESULTS: The cross-validation AUC result on the development dataset was 0.976, 0.931, 0939, and 0.938, and the AUC result on the holdout testing set was 0.978, 0.969, 0.941, and 0.975, for identifying normal macula, MH, ME, and AMD, respectively. CONCLUSIONS: The proposed automated data-driven method successfully identified various macular pathologies (all AUC > 0.94). This method may effectively identify the discriminative features without relying on a potentially error-prone segmentation module.

Current standard quantitative 3D spectral-domain optical coherence tomography (SD-OCT) analyses of various ocular diseases is limited in detecting structural damage at early pathologic stages. This is mostly because only a small fraction of the 3D data is used in the current method of quantifying the structure of interest. This paper presents a novel SD-OCT data analysis technique, taking full advantage of the 3D dataset. The proposed algorithm uses machine classifier to analyze SD-OCT images after grouping adjacent pixels into super pixel in order to detect glaucomatous damage. A 3D SD-OCT image is first converted into a 2D feature map and partitioned into over a hundred super pixels. Machine classifier analysis using boosting algorithm is performed on super pixel features. One hundred and ninety-two 3D OCT images of the optic nerve head region were tested. Area under the receiver operating characteristic (AUC) was computed to evaluate the glaucoma discrimination performance of the algorithm and compare it to the commercial software output. The AUC of normal vs glaucoma suspect eyes using the proposed method was statistically significantly higher than the current method (0.855 and 0.707, respectively, p=0.031). This new method has the potential to improve early detection of glaucomatous structural damages.

PURPOSE: To determine whether there are regional differences in the age-related changes in peripapillary retinal nerve fiber layer (RNFL) thickness as measured by time-domain optical coherence tomography (OCT). METHODS: Fast peripapillary RNFL scans obtained with the Stratus time-domain OCT with nominal diameter of 3.46-mm centered on the optic disc were carried out on 425 normal participants over a wide age range. One eye was randomly selected for scanning or analysis. Average RNFL-, clock hour-, and quadrant-specific rates of RNFL thickness change were calculated and compared. RESULTS: The 425 study participants ranged in age from 18 to 85 years with mean (+/-SD) of 46 (+/-15) years. The mean (+/-SD) average measured RNFL thickness was 104.7 (+/-10.8) micrometers (mum). The decline in the average RNFL thickness was 2.4 mum per decade of age. Changes in RNFL thickness per decade of age ranged from -5.4 (P<0.001) at clock hour 1 to -0.9 (P=0.28) at clock hour 6. Similarly, the rate of thickness change per decade of age in the superior quadrant was -4.3 (P<0.001) versus -1.5 (P=0.006) in the inferior quadrant. The slopes of thinning superiorly and inferiorly were highly significantly different (P=0.001). CONCLUSIONS: The age-related decline in normal RNFL measurements does not occur at equal rates around the disc and occurs mainly superiorly.

Detection of disease progression is an important and challenging component of glaucoma management. Optical coherence tomography (OCT) has proved to be valuable in the detection of glaucomatous damage. With its high resolution and proven measurement reproducibility, OCT has the potential to become an important tool for glaucoma progression detection. This manuscript presents the capabilities of the OCT technology pertinent for detection of progressive glaucomatous damage and provides a review of the current knowledge on the device's clinical performance.

Aqueous humor (AH) exiting the eye via the trabecular meshwork and Schlemm's canal (SC) passes through the deep and intrascleral venous plexus (ISVP) or directly through aqueous veins. The purpose of this study was to visualize the human AH outflow system 360 degrees in three dimensions (3D) during active AH outflow in a virtual casting. The conventional AH outflow pathways of 7 donor eyes were imaged with a modified Bioptigen spectral-domain optical coherence tomography system (Bioptigen Inc, USA; SuperLum LTD, Ireland) at a perfusion pressure of 20 mmHg (N = 3), and 10 mmHg (N = 4). In all eyes, 36 scans (3 equally distributed in each clock hour), each covering a 2 x 3 x 2 mm volume (512 frames, each 512 x 1024 pixels), were obtained. All image data were black/white inverted, and the background subtracted (ImageJ 1.40 g, http://rsb.info.nih.gov/ij/). Contrast was adjusted to isolate the ISVP. SC, collector channels, the deep and ISVP, and episcleral veins were observed throughout the limbus. Aqueous veins could be observed extending into the episcleral veins. Individual scan ISVP castings were rendered and assembled in 3D space in Amira 4.1 (Visage Imaging Inc. USA). A 360-degree casting of the ISVP was obtained in all perfused eyes. The ISVP tended to be dense and overlapping in the superior and inferior quadrants, and thinner in the lateral quadrants. The human AH outflow pathway can be imaged using SD-OCT. The more superficial structures of the AH outflow pathway present with sufficient contrast as to be optically isolated and cast in-situ 360 degrees in cadaver eye perfusion models. This approach may be useful as a model in future studies of human AH outflow.

We address a novel problem domain in the analysis of optical coherence tomography (OCT) images: the diagnosis of multiple macular pathologies in retinal OCT images. The goal is to identify the presence of normal macula and each of three types of macular pathologies, namely, macular edema, macular hole, and age-related macular degeneration, in the OCT slice centered at the fovea. We use a machine learning approach based on global image descriptors formed from a multi-scale spatial pyramid. Our local features are dimension-reduced local binary pattern histograms, which are capable of encoding texture and shape information in retinal OCT images and their edge maps, respectively. Our representation operates at multiple spatial scales and granularities, leading to robust performance. We use 2-class support vector machine classifiers to identify the presence of normal macula and each of the three pathologies. To further discriminate sub-types within a pathology, we also build a classifier to differentiate full-thickness holes from pseudo-holes within the macular hole category. We conduct extensive experiments on a large dataset of 326 OCT scans from 136 subjects. The results show that the proposed method is very effective (all AUC>0.93).

Optical coherence tomography (OCT) techniques have been applied to develop a new generation of the technology, called spectral domain (SD) or Fourier domain (FD) OCT. The commercially available SD-OCT technology offers benefits over the conventional time domain (TD) OCT such as a scanning speed up to 200 times faster and higher axial resolution (3 to 6 mum). Overall, SD-OCT offers improved performance in terms of reproducibility. SD-OCT has a level of discriminating capability, between healthy and perimetric glaucoma eyes similar to that obtained with TD-OCT. Furthermore, the capabilities and features of SD-OCT are rapidly evolving, mainly due to three-dimensional imaging and image rendering. More sophisticated approaches for macular and optic disc assessment are expected to be employed in clinical practice. Analysis software should be further refined for interpretation of SD-OCT images in order to enhance the sensitivity and specificity of glaucoma diagnostics. Most importantly for SD-OCT is determination of its ability to diagnostic structural glaucomatous progression. Considering the recent launch time of the commercially available SD-OCT and slow progressing characteristic of glaucoma, we must wait for longitudinal SD-OCT data, with a long enough follow-up, to become available.

Optical coherence tomography (OCT) imaging has become widespread in ophthalmology over the past 15 years, because of its ability to visualize ocular structures at high resolution. This article reviews the history of OCT imaging of the eye, its current status, and the laboratory work that is driving the future of the technology.

PURPOSE: To investigate the longitudinal effect of optic nerve crush injury in mice by measuring retinal thickness with spectral-domain optical coherence tomography (SD-OCT). METHODS: Optic nerves of one eye from each C57Bl/6 mouse were crushed under direct visualization for 3 seconds, 1 mm posterior to the globe. The optic nerve head (ONH) was imaged with SD-OCT (1.5 x 1.5 x 2.0 mm scan) before the surgical intervention and repeated subsequently for up to 32 days postinjury. A cohort of mice not exposed to the nerve crush procedure served as control. En face SD-OCT images were used to manually align subsequent scans to the baseline en face image. Total retinal thickness (TRT) (along a sampling band with radii 0.33-0.42 mm centered on the ONH) from each follow-up day was automatically quantified for global and sectoral measurements using custom software. Linear mixed-effects models with quadratic terms were fitted to compare TRT of nerve-crushed and control eyes over time. RESULTS: Eleven eyes from 11 nerve crush mice (baseline age 76 +/- 11.8 days) and eight eyes from four healthy mice (baseline age 64 +/- 0 days) were included. The control eyes showed a small, gradual, and consistent TRT increase throughout follow-up. Nerve-crushed eyes showed an initial period of thickening, followed by thinning and slight rebound after day 21. The decrease in thickness observed after the early thickening resolved was statistically significantly different from the control eyes (P < 0.05 for global and sectoral measurements). CONCLUSIONS: SD-OCT can be used to quantitatively monitor changes in retinal thickness in mice over time.