Faculty Bibliography

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 the cutoffs for the interocular difference in retinal nerve fiber layer (RNFL) thickness measured with Cirrus HD-OCT (Carl Zeiss Meditec, Inc) in normal eyes. DESIGN: Observational, clinical study. METHODS: Scans were acquired at 7 academic glaucoma clinics from both eyes of 284 normal subjects using the Optic Disc Cube 200 x 200 protocol. The interocular differences in RNFL thickness were calculated, and normal ranges of interocular differences were determined as the 2.5th and 97.5th percentiles. RESULTS: The average RNFL in the right eye was 0.52 mum thicker than in the left eye; the difference was marginally significant (P = .049). The temporal, nasal, and inferior quadrants had significantly thicker RNFL in the right eye, whereas the left eye showed thicker RNFL in the superior quadrant. The 2.5th and 97.5th percentile interocular difference tolerance limits for average RNFL thickness were -7.9 mum and 8.8 mum, respectively. Although the difference in average RNFL thickness correlated with differences in axial length, disc area, cup-to-disc ratio, and vertical cup-to-disc ratio, only differences in axial length (beta = -0.21; P < .001) and disc area (beta = 0.17; P < .001) were associated with an interocular difference of average RNFL thickness after adjustment for each other. The interocular difference remained stable despite significant decrease in RNFL thickness with aging. CONCLUSIONS: An interocular difference in average RNFL thickness exceeding 9 mum when measured with the Cirrus HD-OCT in normal eyes may be considered statistically significant asymmetry and may be indicative of early glaucomatous damage.

PURPOSE: To determine the ability of optic nerve head (ONH) parameters measured with spectral domain Cirrus HD-OCT (Carl Zeiss Meditec, Inc., Dublin, CA) to discriminate between normal and glaucomatous eyes and to compare them with the discriminating ability of peripapillary retinal nerve fiber layer (RNFL) thickness measurements performed with Cirrus HD-OCT. DESIGN: Evaluation of diagnostic test or technology. PARTICIPANTS: Seventy-three subjects with glaucoma and 146 age-matched normal subjects. METHODS: Peripapillary ONH parameters and RNFL thickness were measured in 1 randomly selected eye of each participant within a 200 x 200 pixel A-scan acquired with Cirrus HD-OCT centered on the ONH. MAIN OUTCOME MEASURES: Optic nerve head topographic parameters, peripapillary RNFL thickness, and area under receiver operating characteristic curves (AUCs). RESULTS: To distinguish normal from glaucomatous eyes, regardless of disease stage, the 6 best parameters (expressed as AUC) were vertical rim thickness (VRT, 0.963), rim area (0.962), RNFL thickness at clock-hour 7 (0.957), RNFL thickness of the inferior quadrant (0.953), vertical cup-to-disc ratio (VCDR, 0.951), and average RNFL thickness (0.950). The AUC for distinguishing between normal eyes and eyes with mild glaucoma was greatest for RNFL thickness of clock-hour 7 (0.918), VRT (0.914), rim area (0.912), RNFL thickness of inferior quadrant (0.895), average RNFL thickness (0.893), and VCDR (0.890). There were no statistically significant differences between AUCs for the best ONH parameters and RNFL thickness measurements (P > 0.05). CONCLUSIONS: Cirrus HD-OCT ONH parameters are able to discriminate between normal eyes and eyes with glaucoma or even mild glaucoma. There is no difference in the ability of ONH parameters and RNFL thickness measurement, as measured with Cirrus OCT, to distinguish between normal and glaucomatous eyes.

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.

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 develop a fully automated algorithm (AP) to perform a volumetric measure of the optic disc using conventional stereoscopic optic nerve head (ONH) photographs, and to compare algorithm-produced parameters with manual photogrammetry (MP), scanning laser ophthalmoscope (SLO) and optical coherence tomography (OCT) measurements. METHODS: One hundred twenty-two stereoscopic optic disc photographs (61 subjects) were analyzed. Disc area, rim area, cup area, cup/disc area ratio, vertical cup/disc ratio, rim volume and cup volume were automatically computed by the algorithm. Latent variable measurement error models were used to assess measurement reproducibility for the four techniques. RESULTS: AP had better reproducibility for disc area and cup volume and worse reproducibility for cup/disc area ratio and vertical cup/disc ratio, when the measurements were compared to the MP, SLO and OCT methods. CONCLUSION: AP provides a useful technique for an objective quantitative assessment of 3D ONH structures.