Faculty Bibliography

PURPOSE: To validate velocity measurements produced by spectral domain optical coherence tomography (SD-OCT) in an in vitro laminar flow model. METHODS: A 30-mL syringe filled with skim milk was inserted into a syringe pump. Intravenous (i.v.) tubing connected the syringe within the pump to a glass capillary tube (internal diameter, 0.579 mm) shallowly embedded in agarose gel, then to a collection reservoir. SD-OCT imaging was performed with an anterior segment eye scanner and optics engine coupled with a 100-nm bandwidth broadband superluminescent diode. Scan density of 128 x 128 A-scans was spread over a 4 x 4 mm area, and each A-scan was 2 mm in length. Fifteen sequential stationary A-scans were obtained at each 128 x 128 position, and Doppler shifts were calculated from temporal changes in phase. The beam-to-flow vector Doppler angle was determined from three-dimensional scans. RESULTS: In all reflectance and Doppler images, a clear laminar flow pattern was observed, with v(max) appearing in the center of the flow column. Phase wrapping was observed at all measured flow velocities, and fringe washout progressively shattered reflectance and phase signals beyond the Nyquist limit. The observed percentages of the velocity profile at or below Nyquist frequency was highly correlated with the predicted percentages (R(2)=0.934; P=0.007). CONCLUSIONS: SD-OCT provides objective Doppler measurements of laminar fluid flow in an in vitro flow system in a range up to the Nyquist limit.

AIMS: The purpose of this study was to compare the day-to-day reproducibility of optical coherence tomography (OCT; StratusOCT, Carl Zeiss Meditec, Dublin, CA) measurements of retinal nerve-fibre layer (RNFL) measurements at time points 1 year apart. METHODS: One eye in each of 11 healthy subjects was examined using the StratusOCT fast RNFL scan protocol. Three fast RNFL scans with signal strength > or =7 were obtained on each of 3 days within a month. This protocol was repeated after 12 months. A linear mixed effects model fitted to the nested data was used to compute the variance components. RESULTS: The square root of the variance component that was attributed to the differences between subjects was 7.17 microm in 2005 and 7.28 microm in 2006. The square roots of the variance component due to differences between days within a single subject were 1.95 microm and 1.50 microm, respectively, and for within day within a single subject were 2.51 microm and 2.55 microm, respectively. There were no statistically significant differences for any variance component between the two testing occasions. CONCLUSIONS: Measurement error variance remains similar from year to year. Day and scan variance component values obtained in a cohort study may be safely applied for prediction of long-term reproducibility.

AIMS: To assess performance of classifiers trained on Heidelberg Retina Tomograph 3 (HRT3) parameters for discriminating between healthy and glaucomatous eyes. METHODS: Classifiers were trained using HRT3 parameters from 60 healthy subjects and 140 glaucomatous subjects. The classifiers were trained on all 95 variables and smaller sets created with backward elimination. Seven types of classifiers, including Support Vector Machines with radial basis (SVM-radial), and Recursive Partitioning and Regression Trees (RPART), were trained on the parameters. The area under the ROC curve (AUC) was calculated for classifiers, individual parameters and HRT3 glaucoma probability scores (GPS). Classifier AUCs and leave-one-out accuracy were compared with the highest individual parameter and GPS AUCs and accuracies. RESULTS: The highest AUC and accuracy for an individual parameter were 0.848 and 0.79, for vertical cup/disc ratio (vC/D). For GPS, global GPS performed best with AUC 0.829 and accuracy 0.78. SVM-radial with all parameters showed significant improvement over global GPS and vC/D with AUC 0.916 and accuracy 0.85. RPART with all parameters provided significant improvement over global GPS with AUC 0.899 and significant improvement over global GPS and vC/D with accuracy 0.875. CONCLUSIONS: Machine learning classifiers of HRT3 data provide significant enhancement over current methods for detection of glaucoma.

MRI has long been applied to clinical medical and neurological cases for the structural assessment of tissues as well as their physiological and functional needs and processes. These uses are at a variety of developmental stages in ophthalmology, from common use of clinical structural assessment for neuro-ophthalmology and evaluation of space-occupying lesions to the beginning stages of experimentally measuring functional activation of specific layers within the retina and measurement of physiological oxygen responses. New MRI methodologies, such as the use of orbital coils and Gd-DTPA image enhancement, have been researched, developed, and validated in the eye, opening new possibilities for this technology to enter the clinic. This review aims to summarize the clinical ophthalmological uses of MRI, focusing on the current use of the technology and future applications.

PURPOSE: To determine the relationship between central corneal thickness (CCT) and retinal nerve fiber layer (RNFL) thickness obtained by scanning laser polarimetry (GDx-VCC; Carl Zeiss Meditec, Dublin, California, USA), confocal scanning laser ophthalmoscopy (HRT II; Heidelberg Engineering, Heidelberg, Germany), and optical coherence tomography (Stratus OCT; Carl Zeiss Meditec). DESIGN: Multicenter clinical trial, retrospective cross-sectional study. METHODS: One hundred and nine healthy subjects from the Advanced Imaging in Glaucoma Study were enrolled in this study. All subjects had a standard clinical examination, including visual field (VF) and good-quality scans from all three imaging devices. CCT was measured using an ultrasonic pachymeter. A linear mixed-effects model was used to assess the relationship between RNFL thickness and CCT, accounting for clustering of eyes within subjects, testing site, ethnicity, family history of glaucoma, axial length intraocular pressure, and VF global indices. RESULTS: For OCT and GDx, there was a slight nonstatistically significant positive relationship between CCT and RNFL thickness. For HRT, there was a slight nonstatistically significant negative relationship between CCT and RNFL thickness. Relationships for each device were found to differ between sites. CONCLUSIONS: CCT was not statistically significantly related to RNFL thickness in healthy eyes.

Study of the structure of the lamina cribrosa is critical in glaucoma research. The purpose of this study is to determine the optimal spectral domain optical coherence tomography imaging protocol for the digital isolation and display of the lamina cribrosa. Three-dimensional datasets centered on the lamina cribrosa were obtained with 200 X 200 to 512 X 512 A-scan densities. The effect of scan density and c-mode slab thickness was subjectively compared. Increasing slab thickness reduced the sharpness of visible prelamina and lamina cribrosa structures. In retrolamina structures, thin slabs provided good visualization, but increased slab size increased the visibility of deeper structures. Scan times as short as 2.3 seconds (256 X 256 A-scans) degraded visualization of the shape of the optic nerve head. The optical scan protocol for lamina cribrosa imaging appears to be a 3 x 3 mm 200 X 200 A-scan volume with the lamina cribrosa positioned near direct current.

PURPOSE: To investigate the effect on optical coherence tomography (OCT) retinal nerve fiber layer (RNFL) thickness measurements of varying the standard 3.4-mm-diameter circle location. METHODS: The optic nerve head (ONH) region of 17 eyes of 17 healthy subjects was imaged with high-speed, ultrahigh-resolution OCT (hsUHR-OCT; 501 x 180 axial scans covering a 6 x 6-mm area; scan time, 3.84 seconds) for a comprehensive sampling. This method allows for systematic simulation of the variable circle placement effect. RNFL thickness was measured on this three-dimensional dataset by using a custom-designed software program. RNFL thickness was resampled along a 3.4-mm-diameter circle centered on the ONH, then along 3.4-mm circles shifted horizontally (x-shift), vertically (y-shift) and diagonally up to +/-500 microm (at 100-microm intervals). Linear mixed-effects models were used to determine RNFL thickness as a function of the scan circle shift. A model for the distance between the two thickest measurements along the RNFL thickness circular profile (peak distance) was also calculated. RESULTS: RNFL thickness tended to decrease with both positive and negative x- and y-shifts. The range of shifts that caused a decrease greater than the variability inherent to the commercial device was greater in both nasal and temporal quadrants than in the superior and inferior ones. The model for peak distance demonstrated that as the scan moves nasally, the RNFL peak distance increases, and as the circle moves temporally, the distance decreases. Vertical shifts had a minimal effect on peak distance. CONCLUSIONS: The location of the OCT scan circle affects RNFL thickness measurements. Accurate registration of OCT scans is essential for measurement reproducibility and longitudinal examination (ClinicalTrials.gov number, NCT00286637).

PURPOSE: To develop automated software for optic nerve head (ONH) quantitative assessment from stereoscopic disc photographs and to evaluate its performance in comparison with human expert assessment. METHODS: A fully automated system, including three-dimensional ONH modeling, disc margin detection, cup margin detection, and calculation of stereometric ONH parameters, was developed and tested. One eye each from 54 subjects (23 healthy, 17 suspected glaucoma, and 14 glaucoma) was enrolled. The majority opinion of three experts defined disc and cup margins on the disc photographs was used for comparison. Seven ONH parameters, disc area, rim area, rim volume, cup area, cup volume, cup-to-disc (C/D) area ratio, and vertical C/D ratio, were computed based on both machine- and expert-defined margins and compared between the methods. RESULTS: All automated ONH measurements showed good correlation with the expert defined margins (Pearson r = 0.90, disc area; 0.56, rim area; 0.78, rim volume; 0.88, cup area; 0.93, cup volume; 0.69, C/D area ratio; and 0.67, vertical C/D ratio; all P or= 0.21). The mean or median of automatically defined disc and cup areas was significantly higher than the subjective assessment (disc area P = 0.0001, t-test; cup area P = 0.036, Wilcoxon signed ranks test), although they had high correlation coefficients. The software failed to detect the disc margin for all the disc photographs with peripapillary atrophy. CONCLUSIONS: The automated ONH analysis method provides an objective and quantitative ONH evaluation using widely available stereo disc photographs.

PURPOSE: To test if improving optical coherence tomography (OCT) resolution and scanning speed improves the visualization of glaucomatous structural changes as compared with conventional OCT. DESIGN: Prospective observational case series. PARTICIPANTS: Healthy and glaucomatous subjects in various stages of disease. METHODS: Subjects were scanned at a single visit with commercially available OCT (StratusOCT) and high-speed ultrahigh-resolution (hsUHR) OCT. The prototype hsUHR OCT had an axial resolution of 3.4 mum (3 times higher than StratusOCT), with an A-scan rate of 24 000 hertz (60 times faster than StratusOCT). The fast scanning rate allowed the acquisition of novel scanning patterns such as raster scanning, which provided dense coverage of the retina and optic nerve head. MAIN OUTCOME MEASURES: Discrimination of retinal tissue layers and detailed visualization of retinal structures. RESULTS: High-speed UHR OCT provided a marked improvement in tissue visualization as compared with StratusOCT. This allowed the identification of numerous retinal layers, including the ganglion cell layer, which is specifically prone to glaucomatous damage. Fast scanning and the enhanced A-scan registration properties of hsUHR OCT provided maps of the macula and optic nerve head with unprecedented detail, including en face OCT fundus images and retinal nerve fiber layer thickness maps. CONCLUSION: High-speed UHR OCT improves visualization of the tissues relevant to the detection and management of glaucoma.