Faculty Bibliography

PURPOSE: To determine the reproducibility of automated segmentation of the three-dimensional (3D) lamina cribrosa (LC) microarchitecture scanned in-vivo using optical coherence tomography (OCT). METHODS: Thirty-nine eyes (8 healthy, 19 glaucoma suspects and 12 glaucoma) from 49 subjects were scanned twice using swept-source (SS-) OCT in a 3.5x3.5x3.64 mm (400x400x896 pixels) volume centered on the optic nerve head, with the focus readjusted after each scan. The LC was automatically segmented and analyzed for microarchitectural parameters, including pore diameter, pore diameter standard deviation (SD), pore aspect ratio, pore area, beam thickness, beam thickness SD, and beam thickness to pore diameter ratio. Reproducibility of the parameters was assessed by computing the imprecision of the parameters between the scans. RESULTS: The automated segmentation demonstrated excellent reproducibility. All LC microarchitecture parameters had an imprecision of less or equal to 4.2%. There was little variability in imprecision with respect to diagnostic category, although the method tends to show higher imprecision amongst healthy subjects. CONCLUSION: The proposed automated segmentation of the LC demonstrated high reproducibility for 3D LC parameters. This segmentation analysis tool will be useful for in-vivo studies of the LC.

PURPOSE: To investigate gold nanorods (GNRs) as a contrast agent to enhance Doppler optical coherence tomography (OCT) imaging of the intrascleral aqueous humor outflow. METHODS: A serial dilution of GNRs was scanned with a spectral-domain OCT device (Bioptigen, Durham, NC) to visualize Doppler signal. Doppler measurements using GNRs were validated using a controlled flow system. To demonstrate an application of GNR enhanced Doppler, porcine eyes were perfused at constant pressure with mock aqueous alone or 1.0x10(12) GNR/mL mixed with mock aqueous. Twelve Doppler and volumetric SD-OCT scans were obtained from the limbus in a radial fashion incremented by 30 degrees , forming a circular scan pattern. Volumetric flow was computed by integrating flow inside non-connected vessels throughout all 12 scans around the limbus. RESULTS: At the GNR concentration of 0.7x10(12) GNRs/mL, Doppler signal was present through the entire depth of the testing tube without substantial attenuation. A well-defined laminar flow profile was observed for Doppler images of GNRs flowing through the glass capillary tube. The Doppler OCT measured flow profile was not statistically different from the expected flow profile based upon an autoregressive moving average model, with an error of -0.025 to 0.037 mm/s (p = 0.6435). Cross-sectional slices demonstrated the ability to view anterior chamber outflow ex-vivo using GNR-enhanced Doppler OCT. Doppler volumetric flow measurements were comparable to flow recorded by the perfusion system. CONCLUSIONS: GNRs created a measureable Doppler signal within otherwise silent flow fields in OCT Doppler scans. Practical application of this technique was confirmed in a constant pressure ex-vivo aqueous humor outflow model in porcine eyes.

PURPOSE: The lamina cribrosa (LC) is a prime location of glaucomatous damage. The purpose of this study was to compare LC 3-dimensional micro-architecture between healthy and glaucomatous eyes in vivo by using optical coherence tomography (OCT). METHODS: Sixty-eight eyes (19 healthy and 49 glaucomatous) from 47 subjects were scanned in a 3.5 x 3.5 x 3.64-mm volume (400 x 400 x 896 pixels) at the optic nerve head by using swept-source OCT. The LC micro-architecture parameters were measured on the visible LC by an automated segmentation algorithm. The LC parameters were compared to diagnosis and visual field mean deviation (VF MD) by using a linear mixed effects model accounting for age. RESULTS: The average VF MD for the healthy and glaucomatous eyes was -0.50 +/- 0.80 dB and -7.84 +/- 8.75 dB, respectively. Beam thickness to pore diameter ratio (P = 0.04) and pore diameter standard deviation (P < 0.01) were increased in glaucomatous eyes. With worse MD, beam thickness to pore diameter ratio (P < 0.01), pore diameter standard deviation (P = 0.05), and beam thickness (P < 0.01) showed a statistically significant increase while pore diameter (P = 0.02) showed a significant decrease. There were no significant interactions between any of the parameters and age (all P > 0.05). CONCLUSIONS: Glaucomatous micro-architecture changes in the LC, detected by OCT analysis, reflect beams remodeling and axonal loss leading to reduction in pore size and increased pore size variability.

PURPOSE: To test the effect of a novel signal normalization method for reducing systematic optical coherence tomography (OCT) measurement differences among multiple spectral-domain (SD) OCT devices. METHODS: A total of 109 eyes from 59 subjects were scanned with two SD-OCT devices (Cirrus and RTVue) at the same visit. Optical coherence tomography image data were normalized to match their signal characteristics between the devices. To compensate signal strength differences, custom high dynamic range (HDR) processing was also applied only to images with substantially lower signal strength. Global mean peripapillary retinal nerve fiber layer (RNFL) thicknesses were then measured automatically from all images using custom segmentation software and were compared to the original device outputs. Structural equation models were used to analyze the absolute RNFL thickness difference between original device outputs and our software outputs after signal normalization. RESULTS: The device-measured RNFL thickness showed a statistically significant difference between the two devices (mean absolute difference 10.58 mum, P < 0.05), while there was no significant difference after normalization on eyes with 62.4-mum or thicker RNFL (mean absolute difference 2.95 mum, P < 0.05). CONCLUSIONS: The signal normalization method successfully reduces the systematic difference in RNFL thickness measurements between two SD-OCT devices. Enabling direct comparison of RNFL thickness obtained from multiple devices would broaden the use of OCT technology in both clinical and research applications.

PURPOSE: We developed a method to normalize optical coherence tomography (OCT) signal profiles from two spectral-domain (SD) OCT devices so that the comparability between devices increases. METHODS: We scanned 21 eyes from 14 healthy and 7 glaucoma subjects with two SD-OCT devices on the same day, with equivalent cube scan patterns centered on the fovea (Cirrus HD-OCT and RTVue). Foveola positions were selected manually and used as the center for registration of the corresponding images. A-scan signals were sampled 1.8 mm from the foveola in the temporal, superior, nasal, and inferior quadrants. After oversampling and rescaling RTVue data along the Z-axis to match the corresponding Cirrus data format, speckle noise reduction and amplitude normalization were applied. For comparison between normalized A-scan profiles, mean absolute difference in amplitude in percentage was measured at each sampling point. As a reference, the mean absolute difference between two Cirrus scans on the same eye also was measured. RESULTS: The mean residual of the A-scan profile amplitude was reduced significantly after signal normalization (12.7% vs. 6.2%, P < 0.0001, paired t-test). All four quadrants also showed statistically significant reduction (all P < 0.0001). Mean absolute difference after normalization was smaller than the one between two Cirrus scans. No performance difference was detected between health and glaucomatous eyes. CONCLUSIONS: The reported signal normalization method successfully reduced the A-scan profile differences between two SD-OCT devices. This signal normalization processing may improve the direct comparability of OCT image analysis and measurement on various devices.

PURPOSE: Ocular imaging devices provide quantitative structural information that might improve glaucoma progression detection. This study examined scanning laser polarimetry (SLP) population-derived versus individual-derived cut-off criteria for detecting progression. METHODS: Forty-eight healthy, glaucoma suspect and glaucoma subjects, providing 76 eyes were used. All subjects had reliable visual field (VF) and SLP scans acquired at the same visits from >/=4 visits. VF progression was defined by guided progression analysis (GPA) and by the VF index. SLP measurements were analysed by fast mode (FM) GPA, compared with the population rate of progression, and extended mode (EM) GPA, compared with the individual variability. The agreement between progression detection methods was measured. RESULTS: Poor agreement was observed between progression defined by VF and FM and EM. The difference in temporal-superior-nasal-inferior-temporal (TSNIT) average rate of change between VF defined progressors and non-progressors for both FM (p=0.010) and EM (p=0.015) was statistically significant. CONCLUSIONS: There is poor agreement between VF and SLP progression regardless of the use of population derived or individual variability criteria. The best SLP progression detection method could not be ascertained, therefore, acquiring three SLP scans per visit is recommended.

PURPOSE: To develop and test a novel signal enhancement method for optical coherence tomography (OCT) images based on the high dynamic range (HDR) imaging concept. METHODS: Three virtual channels, which represent low, medium, and high signal components, were produced for each OCT signal dataset. The dynamic range of each signal component was normalized to the full gray scale range. Finally, the three components were recombined into one image using various weights. Fourteen eyes of 14 healthy volunteers were scanned multiple times using time-domain (TD)-OCT before and while preventing blinking in order to produce a wide variety of signal strength (SS) images on the same eye scanned on the same day. For each eye, a pair of scans with the highest and lowest SS with successful retinal nerve fiber layer (RNFL) segmentation was selected to test the signal enhancement effect. In addition, spectral-domain (SD)-OCT images with poor signal qualities were also processed. RESULTS: Mean SS of good and poor quality scans were 9.0 +/- 1.1 and 4.4 +/- 0.9, respectively. TD-OCT RNFL thickness showed significant differences between good and poor quality scans on the same eye (mean difference 11.9 +/- 6.0 mum, P < 0.0001, paired t-test), while there was no significant difference after signal enhancement (1.7 +/- 6.2 mum, P = 0.33). However, HDR had weaker RNFL compensation effect on images with SS less than or equal to 4, while it maintained good compensation effect on images with SS greater than 4. Successful signal enhancement was also confirmed subjectively on SD-OCT images. CONCLUSION: The HDR imaging successfully restored OCT signal and image quality and reduced RNFL thickness differences due to variable signal level to the level within the expected measurement variability. This technique can be applied to both TD- and SD-OCT images.

We propose a 2D continuous-time Hidden Markov Model (2D CT-HMM) for glaucoma progression modeling given longitudinal structural and functional measurements. CT-HMM is suitable for modeling longitudinal medical data consisting of visits at arbitrary times, and 2D state structure is more appropriate for glaucoma since the time courses of functional and structural degeneration are usually different. The learned model not only corroborates the clinical findings that structural degeneration is more evident than functional degeneration in early glaucoma and the opposite is observed in more advanced stages, but also reveals the exact stages where the trend reverses. A method to detect time segments of fast progression is also proposed. Our results show that this detector can effectively identify patients with rapid degeneration. The model and the derived detector can be of clinical value for glaucoma monitoring.

We demonstrate an automated segmentation method for in-vivo 3D optical coherence tomography (OCT) imaging of the lamina cribrosa (LC). Manual segmentations of coronal slices of the LC were used as a gold standard in parameter selection and evaluation of the automated technique. The method was validated using two prototype OCT devices; each had a subject cohort including both healthy and glaucomatous eyes. Automated segmentation of in-vivo 3D LC OCT microstructure performed comparably to manual segmentation and is useful for investigative research and in clinical quantification of the LC.

PURPOSE: To develop a new three-dimensional (3D) spectral-domain optical coherence tomography (SD-OCT) data analysis method using a machine learning technique based on variable-size super pixel segmentation that efficiently utilizes full 3D dataset to improve the discrimination between early glaucomatous and healthy eyes. METHODS: 192 eyes of 96 subjects (44 healthy, 59 glaucoma suspect and 89 glaucomatous eyes) were scanned with SD-OCT. Each SD-OCT cube dataset was first converted into 2D feature map based on retinal nerve fiber layer (RNFL) segmentation and then divided into various number of super pixels. Unlike the conventional super pixel having a fixed number of points, this newly developed variable-size super pixel is defined as a cluster of homogeneous adjacent pixels with variable size, shape and number. Features of super pixel map were extracted and used as inputs to machine classifier (LogitBoost adaptive boosting) to automatically identify diseased eyes. For discriminating performance assessment, area under the curve (AUC) of the receiver operating characteristics of the machine classifier outputs were compared with the conventional circumpapillary RNFL (cpRNFL) thickness measurements. RESULTS: The super pixel analysis showed statistically significantly higher AUC than the cpRNFL (0.855 vs. 0.707, respectively, p = 0.031, Jackknife test) when glaucoma suspects were discriminated from healthy, while no significant difference was found when confirmed glaucoma eyes were discriminated from healthy eyes. CONCLUSIONS: A novel 3D OCT analysis technique performed at least as well as the cpRNFL in glaucoma discrimination and even better at glaucoma suspect discrimination. This new method has the potential to improve early detection of glaucomatous damage.