Faculty Bibliography

OBJECTIVE: To compare ultrahigh-resolution optical coherence tomography (UHR OCT) with standard-resolution OCT for imaging macular diseases, develop baselines for interpreting OCT images, and identify situations where UHR OCT can provide additional information on disease morphology. DESIGN: Cross-sectional study. PARTICIPANTS: One thousand two eyes of 555 patients with different macular diseases including macular hole, macular edema, central serous chorioretinopathy, age-related macular degeneration (AMD), choroidal neovascularization, epiretinal membrane, retinal pigment epithelium (RPE) detachment, and retinitis pigmentosa. METHODS: A UHR ophthalmic OCT system that achieves 3-microm axial image resolution was developed for imaging in the ophthalmology clinic. Comparative studies were performed with both UHR OCT and standard 10-microm-resolution OCT. Standard scanning protocols of 6 radial 6-mm scans through the fovea were obtained with both systems. Ultrahigh-resolution OCT and standard-resolution OCT images were correlated with standard ophthalmic examination techniques (dilated ophthalmoscopy, fluorescein angiography, indocyanine green angiograms) to assess morphological information contained in the images. MAIN OUTCOME MEASURES: Ultrahigh-resolution and standard-resolution OCT images of macular pathologies. RESULTS: Correlations of UHR OCT images, standard-resolution images, fundus examination, and/or fluorescein angiography were demonstrated in full-thickness macular hole, central serous chorioretinopathy, macular edema, AMD, RPE detachment, epiretinal membrane, vitreal macular traction, and retinitis pigmentosa. Ultrahigh-resolution OCT and standard-resolution OCT exhibited comparable performance in differentiating thicker retinal layers, such as the retinal nerve fiber, inner and outer plexiform, and inner and outer nuclear. Ultrahigh-resolution OCT had improved performance differentiating finer structures or structures with lower contrast, such as the ganglion cell layer and external limiting membrane. Ultrahigh-resolution OCT confirmed the interpretation of features, such as the boundary between the photoreceptor inner and outer segments, which is also visible in standard-resolution OCT. The improved resolution of UHR OCT is especially advantageous in assessing photoreceptor morphology. CONCLUSIONS: Ultrahigh-resolution OCT enhances the visualization of intraretinal architectural morphology relative to standard-resolution OCT. Ultrahigh-resolution OCT images can provide a baseline for defining the interpretation of standard-resolution images, thus enhancing the clinical utility of standard OCT imaging. In addition, UHR OCT can provide additional information on macular disease morphology that promises to improve understanding of disease progression and management.

An upgraded optical coherence tomography system with integrated retinal tracker (TOCT) was developed. The upgraded system uses improved components to extend the tracking bandwidth, fully integrates the tracking hardware into the optical head of the clinical OCT system, and operates from a single software platform. The system was able to achieve transverse scan registration with sub-pixel accuracy (~10 microm). We demonstrate several advanced scan sequences with the TOCT, including composite scans averaged (co-added) from multiple B-scans taken consecutively and several hours apart, en face images collected by summing the A-scans of circular, line, and raster scans, and three-dimensional (3D) retinal maps of the fovea and optic disc. The new system achieves highly accurate OCT scan registration yielding composite images with significantly improved spatial resolution, increased signal-to-noise ratio, and reduced speckle while maintaining well-defined boundaries and sharp fine structure compared to single scans. Precise re-registration of multiple scans over separate imaging sessions demonstrates TOCT utility for longitudinal studies. En face images and 3D data cubes generated from these data reveal high fidelity image registration with tracking, despite scan durations of more than one minute.

PURPOSE: To develop a software algorithm to perform automated segmentation of retinal layer structures on linear macular optical coherence tomography (StratusOCT; Carl Zeiss Meditec, Inc., Dublin, CA) scan images and to test its performance in discriminating normal from glaucomatous eyes in comparison with conventional circumpapillary nerve fiber layer (cpNFL) thickness measurement. METHODS: Four layer structures within the retina were defined: the macular nerve fiber layer (mNFL), the inner retinal complex (IRC; retinal ganglion cell [RGC] layer + inner plexiform and nuclear layers), outer plexiform layer (OPL), and outer retinal complex (ORC; outer nuclear layer + photoreceptor layer). Normal and glaucomatous eyes underwent fast macular map and fast NFL OCT scans. Linear macular images were analyzed using the developed algorithm, and the results were compared with the cpNFL thickness measurement. RESULTS: Forty-seven subjects (23 normal and 24 with glaucoma) were analyzed. mNFL, cpNFL, IRC, and the total retinal thicknesses were significantly greater in normal than in glaucomatous eyes (P < or = 0.0002; Wilcoxon), whereas OPL thickness did not show a significant difference (P = 0.46). ORC thickness was significantly greater in glaucomatous than normal eyes (P = 0.035). Areas under the receiver operator characteristic curve (AROCs) for discriminating normal from glaucomatous eyes were highest with mNFL + IRC (0.97) and lowest with OPL (0.56). AROCs for OPL and ORC were significantly smaller than those for mNFL, IRC, mNFL+IRC, and cpNFL (P < or = 0.01). AROCs for IRC, mNFL + IRC, and cpNFL were significantly larger than for retinal thickness (P < or = 0.049). Among the best-performing parameters (mNFL, IRC, mNFL + IRC, and cpNFL) there was no significant difference in AROCs (P > or = 0.15). CONCLUSIONS: The newly developed macular segmentation algorithm described herein demonstrated its ability to quantify objectively the glaucomatous damage to RGCs and NFL and to discriminate between glaucomatous and normal eyes. Further algorithm refinement and improvements in resolution and image quality may yield a more powerful methodology for clinical glaucoma evaluation.

OBJECTIVES: To longitudinally evaluate optical coherence tomography (OCT) peripapillary retinal nerve fiber layer thickness measurements and to compare these measurements across time with clinical status and automated perimetry. METHODS: Retrospective evaluation of 64 eyes (37 patients) of glaucoma suspects or patients with glaucoma participating in a prospective longitudinal study. All participants underwent comprehensive clinical assessment, visual field (VF) testing, and OCT every 6 months. Field progression was defined as a reproducible decline of at least 2 dB in VF mean deviation from baseline. Progression of OCT was defined as reproducible mean retinal nerve fiber layer thinning of at least 20 mum. RESULTS: Each patient had a median of 5 usable OCT scans at median follow-up of 4.7 years. The difference in the linear regression slopes of retinal nerve fiber layer thickness between glaucoma suspects and patients with glaucoma was nonsignificant for all variables; however, Kaplan-Meier survival curve analysis demonstrated a higher progression rate by OCT vs VF. Sixty-six percent of eyes were stable throughout follow-up, whereas 22% progressed by OCT alone, 9% by VF mean deviation alone, and 3% by VF and OCT. CONCLUSIONS: A greater likelihood of glaucomatous progression was identified by OCT vs automated perimetry. This might reflect OCT hypersensitivity or true damage identified by OCT before detection by conventional methods.

An active, hardware-based retinal tracker is integrated with a clinical optical coherence tomography (OCT) system to investigate the effects of stabilization on acquisition of high-resolution retinal sections. The prototype retinal tracker locks onto common fundus features, detects transverse eye motion via changes in feature reflectance, and positions the OCT diagnostic beam to fixed coordinates on the retina with mirrors driven by a feedback control loop. The system is tested in a full clinical protocol on subjects with normal and glaucomatous eyes. Experimental analysis software is developed to coalign and coadd multiple fundus and OCT images and to extract quantitative information on the location of structures in the images. Tracking is highly accurate and reproducible on all but one subject, resulting in the ability to scan the same retinal location continually over long periods of time. The results show qualitative improvement in 97% of coadded OCT scans and a reduction in the variance of the position of the optic disc cup edge to less than 1 pixel (< 60 microm). The tracking system can be easily configured for use in research on ultra-high-resolution OCT systems for advanced image modalities. For example, tracking will enable very high density 3-D scans of the retina, which are susceptible to eye motion artifacts even for new high-speed systems.

OBJECTIVE: Optical coherence tomography (OCT) has been shown to be a valuable tool in glaucoma assessment. We investigated a new ultrahigh-resolution OCT (UHR-OCT) imaging system in glaucoma patients and compared the findings with those obtained by conventional-resolution OCT. DESIGN: Retrospective comparative case series. PARTICIPANTS: A normal subject and 4 glaucoma patients representing various stages of glaucomatous damage. TESTING: All participants were scanned with StratusOCT (axial resolution of approximately 10 mum) and UHR-OCT (axial resolution of approximately 3 microm) at the same visit. MAIN OUTCOME MEASURE: Comparison of OCT findings detected with StratusOCT and UHR-OCT. RESULTS: Ultrahigh-resolution OCT provides a detailed cross-sectional view of the scanned retinal area that allows differentiation between retinal layers. These UHR images were markedly better than those obtained by the conventional-resolution OCT. CONCLUSIONS: Ultrahigh-resolution OCT provides high-resolution images of the ocular posterior segment, which improves the ability to detect retinal abnormalities due to glaucoma.

PURPOSE: Several cross-sectional studies have demonstrated the capability of optical coherence tomography (OCT) to detect glaucomatous changes. OCT enables posterior pole scanning of three regions: macula, peripapillary, and optic nerve head (ONH). This study compared the ability of each region to detect glaucomatous damage. DESIGN: Retrospective observational cross-sectional study. METHODS: The study included 37 normal (37 subjects) and 37 glaucomatous eyes (26 subjects) that had comprehensive ocular examination, reliable and reproducible Swedish interactive thresholding algorithm standard 24-2 perimetry, and Stratus OCT scanning of macula, peripapillary, and ONH regions on the same visit. Optical nerve head (ONH) appearance did not form part of the inclusion criteria. The main outcome measure, was area under receiver operating characteristic curves (AROCs) that was calculated for each scanning region for distinguishing between normal and glaucomatous eyes. RESULTS: The highest AROCs for distinguishing between groups were for ONH parameters (rim area = 0.97, horizontal integrated rim width = 0.96, vertical integrated rim area = 0.95) and peripapillary nerve fiber layer (NFL) thickness (0.94) followed by macular volume and thickness (both 0.80). A statistically significant difference existed in ONH and NFL AROCs when compared with macular AROCs (P < or = .007, for both) CONCLUSIONS: OCT ONH and NFL parameters provided similar discrimination capabilities between healthy eyes and those of glaucoma patients and superior discrimination capabilities when compared with macular parameters.