Faculty Bibliography

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.

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.

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.

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.

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 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.

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.