Faculty Bibliography

We have developed a new image-based guidance system for microsurgery using optical coherence tomography (OCT), which presents a virtual image in its correct location inside the scanned tissue. Applications include surgery of the cornea, skin, and other surfaces below which shallow targets may advantageously be displayed for the naked eye or low-power magnification by a surgical microscope or loupes (magnifying eyewear). OCT provides real-time high-resolution (3 micron) images at video rates within a two or more millimeter axial range in soft tissue, and is therefore suitable for guidance to various shallow targets such as Schlemm's canal in the eye (for treating Glaucoma) or skin tumors. A series of prototypes of the "OCT penlight" have produced virtual images with sufficient resolution and intensity to be useful under magnification, while the geometrical arrangement between the OCT scanner and display optics (including a half-silvered mirror) permits sufficient surgical access. The two prototypes constructed thus far have used, respectively, a miniature organic light emitting diode (OLED) display and a reflective liquid crystal on silicon (LCoS) display. The OLED has the advantage of relative simplicity, satisfactory resolution (15 micron), and color capability, whereas the LCoS can produce an image with much higher intensity and superior resolution (12 micron), although it is monochromatic and more complicated optically. Intensity is a crucial limiting factor, since light flux is greatly diminished with increasing magnification, thus favoring the LCoS as the more practical system.

PURPOSE: To map ganglion cell complex (GCC) thickness with high-speed Fourier-domain optical coherence tomography (FD-OCT) and compute novel macular parameters for glaucoma diagnosis. DESIGN: Observational, cross-sectional study. PARTICIPANTS: One hundred seventy-eight participants in the Advanced Imaging for Glaucoma Study, divided into 3 groups: 65 persons in the normal group, 78 in the perimetric glaucoma group (PG), and 52 in the preperimetric glaucoma group (PPG). METHODS: The RTVue FD-OCT system was used to map the macula over a 7 x 6 mm region. The macular OCT images were exported for automatic segmentation using software we developed. The program measured macular retinal (MR) thickness and GCC thickness. The GCC was defined as the combination of nerve fiber, ganglion cell, and inner plexiform layers. Pattern analysis was applied to the GCC map and the diagnostic powers of pattern-based diagnostic parameters were investigated. Results were compared with time-domain (TD) Stratus OCT measurements of MR and circumpapillary nerve fiber layer (NFL) thickness. MAIN OUTCOME MEASURES: Repeatability was assessed by intraclass correlation, pooled standard deviation, and coefficient of variation. Diagnostic power was assessed by the area under the receiver operator characteristic (AROC) curve. Measurements in the PG group were the primary measures of performance. RESULTS: The FD-OCT measurements of MR and GCC averages had significantly better repeatability than TD-OCT measurements of MR and NFL averages. The FD-OCT GCC average had significantly (P = 0.02) higher diagnostic power (AROC = 0.90) than MR (AROC = 0.85 for both FD-OCT and TD-OCT) in differentiating between PG and normal. One GCC pattern parameter, global loss volume, had significantly higher AROC (0.92) than the overall average (P = 0.01). The diagnostic powers of the best GCC parameters were statistically equal to TD-OCT NFL average. CONCLUSIONS: The higher speed and resolution of FD-OCT improved the repeatability of macular imaging compared with standard TD-OCT. Ganglion cell mapping and pattern analysis improved diagnostic power. The improved diagnostic power of macular GCC imaging is on par with, and complementary to, peripapillary NFL imaging. Macular imaging with FD-OCT is a useful method for glaucoma diagnosis and has potential for tracking glaucoma progression.

AIM: To evaluate, within ocular imaging scans of acceptable quality as determined by manufacturers' guidelines, the effects of image quality on glaucoma discrimination capabilities. METHODS: One hundred and four healthy and 75 glaucomatous eyes from the Advanced Imaging in Glaucoma Study (AIGS) were imaged with GDx-VCC, HRT II and StratusOCT. Quality score (QS>/=8), pixel standard deviation (SD/=5) were used as quality parameter cut-offs, respectively. GDx nerve fibre indicator (NFI) and HRT Moorfields regression analysis (MRA) classifications and OCT mean retinal nerve fibre layer (RNFL) thickness were used as the discriminatory parameters. Logistic regression models were used to model the dichotomous clinical classification (healthy vs glaucoma) as a function of image-quality parameters and discriminatory parameters. RESULTS: Quality parameter covariates were statistically non-significant for GDx and HRT but had an inverse effect on OCT in predicting disease (a higher SS had a lower probability of glaucoma). Age was a significant covariate for GDx and HRT, but not OCT, while ethnicity and interaction between the image quality and the institute where scans were acquired were significant covariates in the OCT models. CONCLUSION: Scan quality within the range recommended as acceptable by the manufacturer of each imaging device does not affect the glaucoma discriminating ability of GDx or HRT but does affect Stratus OCT glaucoma discrimination.

BACKGROUND/AIMS: To investigate retinal nerve fibre layer (RNFL) thickness measurement reproducibility using conventional time-domain optical coherence tomography (TD-OCT) and spectral-domain OCT (SD-OCT), and to evaluate two methods defining the optic nerve head (ONH) centring: Centred Each Time (CET) vs Centred Once (CO), in terms of RNFL thickness measurement variability on SD-OCT. METHODS: Twenty-seven eyes (14 healthy subjects) had three circumpapillary scans with TD-OCT and three raster scans (three-dimensional or 3D image data) around ONH with SD-OCT. SD-OCT images were analysed in two ways: (1) CET: ONH centre was defined on each image separately and (2) CO: ONH centre was defined on one image and exported to other images after scan registration. After defining the ONH centre, a 3.4 mm diameter virtual circular OCT was resampled on SD-OCT images to mimic the conventional circumpapillary RNFL thickness measurements taken with TD-OCT. RESULTS: CET and CO showed statistically significantly better reproducibility than TD-OCT except for 11:00 with CET. CET and CO methods showed similar reproducibility. CONCLUSIONS: SD-OCT 3D cube data generally showed better RNFL measurement reproducibility than TD-OCT. The choice of ONH centring methods did not affect RNFL measurement reproducibility.

PURPOSE: To determine the effects of age on global and sectoral peripapillary retinal nerve fiber layer (RNFL), macular thicknesses, and optic nerve head (ONH) parameters in healthy subjects using optical coherence tomography (OCT). DESIGN: Retrospective, cross-sectional observational study. PARTICIPANTS: A total of 226 eyes from 124 healthy subjects were included. METHODS: Healthy subjects were scanned using the Fast RNFL, Fast Macula, and Fast ONH scan patterns on a Stratus OCT (Carl Zeiss Meditec, Dublin, CA). All global and sectoral RNFL and macular parameters and global ONH parameters were modeled in terms of age using linear mixed effects models. Normalized slopes were also calculated by dividing the slopes by the mean value of the OCT parameter for interparameter comparison. MAIN OUTCOME MEASURES: Slope of each OCT parameter across age. RESULTS: All global and sectoral RNFL thickness parameters statistically significantly decreased with increasing age, except for the temporal quadrant and clock hours 8 to 10, which were not statistically different from a slope of zero. Highest absolute slopes were in the inferior and superior quadrant RNFL and clock hour 1 (superior nasal). Normalized slopes showed a similar rate in all sectors except for the temporal clock hours (8-10). All macular thickness parameters statistically significantly decreased with increasing age, except for the central fovea sector, which had a slight positive slope that was not statistically significant. The nasal outer sector had the greatest absolute slope. Normalized macular slope in the outer ring was similar to the normalized slopes in the RNFL. Normalized inner ring had shallower slope than the outer ring with a similar rate in all quadrants. Disc area remained nearly constant across the ages, but cup area increased and rim area decreased with age, both of which were statistically significant. CONCLUSIONS: Global and regional changes caused by the effects of age on RNFL, macula, and ONH OCT measurements should be considered when assessing eyes over time. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Optical coherence tomography has allowed unprecedented visualization of ocular structures, but the identity of some visible objects within slices remains unknown. This study reconstructs a number of those objects in 3D space, allowing their identification by observation of their 3D morphology. In the case mottling deep within image slices through the optic disc, C-mode imaging provided visualization of the appearance and distribution of laminar pores. In the case of white spots and streaks sometimes observed in image slices through the cornea, C-mode imaging contoured to the path of those white spots allowed their visual identification as nerves extending radially into the cornea from the limbus. White spots observed in ultra-high resolution retinal image slices were identified as blood within retinal capillaries. C-mode contour-corrected imaging of three dimensional structures provided the identification of previously unidentified structures visible in cross-sectional image slices.

PURPOSE: To develop a semiautomated method to visualize structures of interest (SoIs) along their contour within three-dimensional, spectral domain optical coherence tomography (3D SD-OCT) data, without the need for segmentation. METHODS: With the use of two SD-OCT devices, the authors obtained 3D SD-OCT data within 6 x 6 x 1.4-mm and 6 x 6 x 2-mm volumes, respectively, centered on the fovea in healthy eyes and in eyes with retinal pathology. C-mode images were generated by sampling a variable thickness plane semiautomatically modeled to fit the contour of the SoI. Unlike published and commercialized methods, this method did not require retinal layer segmentation, which is known to fail frequently in the presence of retinal pathology. Four SoIs were visualized for healthy eyes: striation of retinal nerve fiber (RNF), retinal capillary network (RCN), choroidal capillary network (CCN), and major choroidal vasculature (CV). Various SoIs were visualized for eyes with retinal pathology. RESULTS: Seven healthy eyes and seven eyes with retinal pathology (cystoid macular edema, central serous retinopathy, vitreoretinal traction, and age-related macular degeneration) were imaged. CCN and CV were successfully visualized in all eyes, whereas RNF and RCN were visualized in all healthy eyes and in 42.8% of eyes with pathologies. Various SoIs were successfully visualized in all eyes with retinal pathology. CONCLUSIONS: The proposed C-mode contour modeling may provide clinically useful images of SoIs even in eyes with severe pathologic changes in which segmentation algorithms fail.

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.

BACKGROUND: Glaucoma is a group of diseases characterised by retinal ganglion cell dysfunction and death. Detection of glaucoma and its progression are based on identification of abnormalities or changes in the optic nerve head (ONH) or the retinal nerve fibre layer (RNFL), either functional or structural. This review will focus on the identification of structural abnormalities in the RNFL associated with glaucoma. DISCUSSION: A variety of new techniques have been created and developed to move beyond photography, which generally requires subjective interpretation, to quantitative retinal imaging to measure RNFL loss. Scanning laser polarimetry uses polarised light to measure the RNFL birefringence to estimate tissue thickness. Optical coherence tomography (OCT) uses low-coherence light to create high-resolution tomographic images of the retina from backscattered light in order to measure the tissue thickness of the retinal layers and intraretinal structures. Segmentation algorithms are used to measure the thickness of the retinal nerve fibre layer directly from the OCT images. In addition to these clinically available technologies, new techniques are in the research stages. Polarisation-sensitive OCT has been developed that combines the strengths of scanning laser polarimetry with those of OCT. Ultra-fast techniques for OCT have been created for research devices. The continued utilisation of imaging devices into the clinic is refining glaucoma assessment. In the past 20 years glaucoma has gone from a disease diagnosed and followed using highly subjective techniques to one measured quantitatively and increasingly objectively.