Faculty Bibliography

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 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.

PURPOSE: To visualize, quantitatively assess, and interpret outer retinal morphology by using high-speed, ultrahigh-resolution (UHR) OCT. METHODS: Retinal imaging was performed in the ophthalmic clinic in a cross-section of 43 normal subjects with a 3.5-microm, axial-resolution, high-speed, UHR OCT prototype instrument, using a radial scan pattern (24 images, 1500 axial scans). Outer retinal layers were automatically segmented and measured. High-definition imaging was performed with a 2.8-microm axial-resolution, high-speed, UHR OCT research prototype instrument, to visualize the finer features in the outer retina. RESULTS: Quantitative maps of outer retinal layers showed clear differences between the cone-dominated fovea and the rod-dominated parafovea and perifovea, indicating that photoreceptor morphology can explain the appearance of the outer retina in high-speed, UHR OCT images. Finer, scattering bands were visualized in the outer retina using high-definition imaging and were interpreted by comparison to known anatomy. CONCLUSIONS: High-speed UHR OCT enables quantification of scattering layers in the outer retina. An interpretation of these features is presented and supported by quantitative measurements in normal subjects and comparison with known anatomy. The thick scattering region of the outer retina previously attributed to the retinal pigment epithelium (RPE) is shown to consist of distinct scattering bands corresponding to the photoreceptor outer segment tips, RPE, and Bruch's membrane. These results may advance understanding of the outer retinal appearance in OCT images. The normative measurements may also aid in future investigations of outer retinal changes in age-related macular degeneration and other diseases.

Excessive retinal vascular permeability contributes to the pathogenesis of proliferative diabetic retinopathy and diabetic macular edema, leading causes of vision loss in working-age adults. Using mass spectroscopy-based proteomics, we detected 117 proteins in human vitreous and elevated levels of extracellular carbonic anhydrase-I (CA-I) in vitreous from individuals with diabetic retinopathy, suggesting that retinal hemorrhage and erythrocyte lysis contribute to the diabetic vitreous proteome. Intravitreous injection of CA-I in rats increased retinal vessel leakage and caused intraretinal edema. CA-I-induced alkalinization of vitreous increased kallikrein activity and its generation of factor XIIa, revealing a new pathway for contact system activation. CA-I-induced retinal edema was decreased by complement 1 inhibitor, neutralizing antibody to prekallikrein and bradykinin receptor antagonism. Subdural infusion of CA-I in rats induced cerebral vascular permeability, suggesting that extracellular CA-I could have broad relevance to neurovascular edema. Inhibition of extracellular CA-I and kallikrein-mediated innate inflammation could provide new therapeutic opportunities for the treatment of hemorrhage-induced retinal and cerebral edema.

We present a computationally efficient, semiautomated method for analysis of posterior retinal layers in three-dimensional (3-D) images obtained by spectral optical coherence tomography (SOCT). The method consists of two steps: segmentation of posterior retinal layers and analysis of their thickness and distance from an outer retinal contour (ORC), which is introduced to approximate the normal position of external interface of the healthy retinal pigment epithelium (RPE). The algorithm is shown to effectively segment posterior retina by classifying every pixel in the SOCT tomogram using the similarity of its surroundings to a reference set of model pixels from user-selected area(s). Operator intervention is required to assess the quality of segmentation. Thickness and distance maps from the segmented layers and their analysis are presented for healthy and pathological retinas.

A 42-year-old man with Hunter syndrome developed bilateral visual field loss. Visual field testing demon-strated bilateral ring scotomata that corresponded to areas of thinning seen on standard resolution optical coherence tomography. High-speed, ultrahigh resolution optical coherence tomography, capable of 3.5-micron axial resolution, showed a loss of photoreceptors outside the fovea and cystoid spaces within the inner nuclear, ganglion cell, and outer nuclear layers. These results were consistent with histopathologic features that have been reported previously in patients with Hunter syndrome. Optical coherence tomography could be used as a diagnostic modality to monitor patients with Hunter syndrome and to detect subclinical forms of disease.

OBJECTIVE: To introduce new corneal high-speed, ultra-high-resolution optical coherence tomography (hsUHR-OCT) technology that improves the evaluation of complicated and uncomplicated cataract, corneal, and refractive surgical procedures. DESIGN: This case series included a control subject and 9 eyes of 8 patients who had undergone phacoemulsification, Descemet membrane stripping endokeratoplasty, corneal implantation for keratoconus, and complicated and uncomplicated laser in situ keratomileusis. These eyes underwent imaging using a prototype ophthalmic hsUHR-OCT system. All the scans were compared with conventional slitlamp biomicroscopy. RESULTS: Cross-sectional hsUHR-OCT imaging allowed in vivo differentiation of corneal layers and existing pathologic abnormalities at ultrahigh axial image resolution. These images illustrate the various incisional and refractive interfaces created with corneal procedures. CONCLUSIONS: The magnified view of the cornea using hsUHR-OCT is helpful in conceptualizing and understanding basic and complicated clinical pathologic features; hsUHR-OCT has the potential to become a powerful, noninvasive clinical corneal imaging modality that can enhance surgical management. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00343473.