Faculty Bibliography

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.

PURPOSE: To test the reproducibility of spectral-domain optical coherence tomography (SD-OCT) total retinal thickness (TRT) measurements in mice. METHODS: C57Bl/6 mice were anesthetized, and three repeated volumetric images were acquired in both eyes with SD-OCT (250 A-scans x 250 frames x 1024 samplings), centered on the optic nerve head (ONH). The mice were repositioned between scans. TRT was automatically measured within a sampling band of retinal thickness with radii of 55 to 70 pixels, centered on the ONH by using custom segmentation software. The first volumetric image acquired in a given eye was used to register the remaining two SD-OCT images by manually aligning the en face images with respect to rotation and linear translation. Linear mixed-effects models were fitted to global and quadrant thicknesses, taking into account the clustering between eyes, to assess imprecision (measurement reproducibility). RESULTS: Twenty-six eyes of 13 adult mice (age 13 weeks) were imaged. The mean global TRT across all eyes was 298.21 mum, with a mouse heterogeneity standard deviation (SD) of 4.88 mum (coefficient of variation [CV] = 0.016), an eye SD of 3.32 mum (CV = 0.011), and a device-related imprecision SD of 2.33 mum (CV = 0.008). The superior quadrant had the thickest mean TRT measurement (310.38 mum) and the highest (worst) imprecision SD (3.13 mum; CV = 0.010), and the inferior quadrant had the thinnest mean TRT (291.55 mum). The quadrant with the lowest (best) imprecision SD was in the nasal one (2.06 mum; CV = 0.007). CONCLUSIONS: Good reproducibility was observed for SD-OCT retinal thickness measurements in mice. SD-OCT may be useful for in vivo longitudinal studies in mice.

BACKGROUND AND OBJECTIVE: Digital pathology has thus far focused on producing digital images of glass microscope slides. Spectral domain optical coherence tomography (SD-OCT) can be used to directly scan tissue blocks to produce three-dimensional histology images, potentially bypassing glass slide workflow. MATERIALS AND METHODS: Formalin-fixed paraffin-embedded tissue blocks were scanned using SD-OCT and resulting images were compared with corresponding areas on microscope slides. RESULTS: Low-magnification features were recognizable, including tissue outlines, fat, vessels, and outlines of colonic mucosal crypts. Subtle textures that were suggestive of benign breast lobules and ovarian tumor features were also visible. Initial SD-OCT images lacked resolution and contrast relative to traditional microscopy, but the image content suggests that additional features of interest are present and may be revealed with improved SD-OCT resolution and more post-processing experience. Elucidation of three-dimensional histology and pathology are also future tasks. CONCLUSION: Eventual availability of diagnostic-quality three-dimensional histology would have a profound impact on anatomic pathology.

Three dimensional (3D) ophthalmic imaging using optical coherence tomography (OCT) has revolutionized assessment of the eye, the retina in particular. Recent technological improvements have made the acquisition of 3D-OCT datasets feasible. However, while volumetric data can improve disease diagnosis and follow-up, novel image analysis techniques are now necessary in order to process the dense 3D-OCT dataset. Fundamental software improvements include methods for correcting subject eye motion, segmenting structures or volumes of interest, extracting relevant data post hoc and signal averaging to improve delineation of retinal layers. In addition, innovative methods for image display, such as C-mode sectioning, provide a unique viewing perspective and may improve interpretation of OCT images of pathologic structures. While all of these methods are being developed, most remain in an immature state. This review describes the current status of 3D-OCT scanning and interpretation, and discusses the need for standardization of clinical protocols as well as the potential benefits of 3D-OCT scanning that could come when software methods for fully exploiting these rich datasets are available clinically. The implications of new image analysis approaches include improved reproducibility of measurements garnered from 3D-OCT, which may then help improve disease discrimination and progression detection. In addition, 3D-OCT offers the potential for preoperative surgical planning and intraoperative surgical guidance.

We demonstrate ultrahigh speed swept source/Fourier domain ophthalmic OCT imaging using a short cavity swept laser at 100,000 - 400,000 axial scan rates. Several design configurations illustrate tradeoffs in imaging speed, sensitivity, axial resolution, and imaging depth. Variable rate A/D optical clocking is used to acquire linear-in-k OCT fringe data at 100 kHz axial scan rate with 5.3 um axial resolution in tissue. Fixed rate sampling at 1 GSPS achieves a 7.5mm imaging range in tissue with 6.0 um axial resolution at 100 kHz axial scan rate. A 200 kHz axial scan rate with 5.3 um axial resolution over 4mm imaging range is achieved by buffering the laser sweep. Dual spot OCT using two parallel interferometers achieves 400 kHz axial scan rate, almost 2X faster than previous 1050 nm ophthalmic results and 20X faster than current commercial instruments. Superior sensitivity roll-off performance is shown. Imaging is demonstrated in the human retina and anterior segment. Wide field 12x12 mm data sets include the macula and optic nerve head. Small area, high density imaging shows individual cone photoreceptors. The 7.5 mm imaging range configuration can show the cornea, iris, and anterior lens in a single image. These improvements in imaging speed and depth range provide important advantages for ophthalmic imaging. The ability to rapidly acquire 3D-OCT data over a wide field of view promises to simplify examination protocols. The ability to image fine structures can provide detailed information on focal pathologies. The large imaging range and improved image penetration at 1050 m wavelengths promises to improve performance for instrumentation which images both the retina and anterior eye. These advantages suggest that swept source OCT at 1050 nm wavelengths will play an important role in future ophthalmic instrumentation.

PURPOSE: Measurements of human Schlemm's canal (SC) have been limited to histologic sections. The purpose of this study was to demonstrate noninvasive measurements of aqueous outflow (AO) structures in the human eye, examining regional variation in cross-sectional SC areas (on/off collector channel [CC] ostia [SC/CC] and nasal/temporal) in the eyes of living humans. METHODS: SC was imaged by spectral-domain optical coherence tomography with a 200-nm bandwidth light source. Both eyes of 21 healthy subjects and one glaucomatous eye of three subjects were imaged nasally and temporally. Contrast and magnification were adjusted to maximize visualization. Cross-sectional SC on and off SC/CC was traced three times by two independent masked observers using ImageJ (ImageJ 1.40g, http://rsb.info.nih.gov/ij/ Wayne Rasband, developer, National Institutes of Health, Bethesda, MD). The mean SC area was recorded. A linear mixed-effects model was used to analyze eye, nasal/temporal laterality, and SC area on or off SC/CC. RESULTS: SC area was significantly larger on SC/CCs than off (12,890 vs. 7,391 micorm(2), P < 0.0001) and was significantly larger on the nasal side than on the temporal (10,983 vs. 8,308 micorm(2), P = 0.009). SC areas were significantly smaller in glaucoma patients than in normal subjects, whether pooled (P = 0.0073) or grouped by on (P = 0.0215) or off (P = 0.0114) SC/CC. CONCLUSIONS: Aqueous outflow structures, including SC and CCs, can be noninvasively assessed in the human eye. These measurements will be useful in physiological studies of AO and will be clinically useful in the determination of the impact of glaucoma therapies on IOP as well as presurgical planning.

PURPOSE. To investigate the characteristics of a spectral-domain optical coherence tomography (SD-OCT) image phenomenon known as the mirror artifact, calculate its prevalence, analyze potential risk factors, measure severity, and correlate it to spherical equivalent and central visual acuity (VA). METHODS. OCT macular cube 512 x 128 scans taken between January 2008 and February 2009 at the New England Eye Center were analyzed for the presence of mirror artifacts. Artifact severity was determined by the degree of segmentation breakdown that it caused on the macular map. A retrospective review was conducted of the medical records of patients with artifacts and of a random control group without artifacts. RESULTS. Of 1592 patients, 9.3% (148 patients, 200 eyes) had scans that contained mirror artifacts. A significantly more myopic spherical equivalent (P < 0.001), worse VA (P < 0.001), longer axial lengths (P = 0.004), and higher proportions of moderate to high myopia (P < 0.001) were found in patients with mirror artifacts than in patients without artifacts. Worse VA was associated with increased artifact severity (P = 0.04). CONCLUSIONS. In all scans analyzed, a high prevalence of mirror artifacts was found. This image artifact was often associated with patients with moderate to high myopia. Improvements in instrumentation may be necessary to resolve this problem in moderately and highly myopic eyes. Operators should be advised to properly position the retina when scanning eyes. In cases in which peripheral abnormalities in topographic measurements of retinal thickness are found, corresponding OCT scans should be examined for the presence of mirror artifacts.