Faculty Bibliography

OBJECTIVE: To determine the correspondence between optic disc margins evaluated using disc photography (DP) and optical coherence tomography (OCT). METHODS: From May 1, 2005, through November 10, 2005, 17 healthy volunteers (17 eyes) had raster scans (180 frames, 501 samplings per frame) centered on the optic disc taken with stereo-optic DP and high-speed ultrahigh-resolution OCT (hsUHR-OCT). Two image outputs were derived from the hsUHR-OCT data set: an en face hsUHR-OCT fundus image and a set of 180 frames of cross-sectional images. Three ophthalmologists independently and in a masked, randomized fashion marked the disc margin on the DP, hsUHR-OCT fundus, and cross-sectional images using custom software. Disc size (area and horizontal and vertical diameters) and location of the geometric disc center were compared among the 3 types of images. RESULTS: The hsUHR-OCT fundus image definition showed a significantly smaller disc size than the DP definition (P <.001, mixed-effects analysis). The hsUHR-OCT cross-sectional image definition showed a significantly larger disc size than the DP definition (P <.001). The geometric disc center location was similar among the 3 types of images except for the y-coordinate, which was significantly smaller in the hsUHR-OCT fundus images than in the DP images. CONCLUSION: The optic disc margin as defined by hsUHR-OCT was significantly different than the margin defined by DP.

A scanning laser ophthalmoscopy (SLO) image, taken from optical coherence tomography (OCT), usually has lower global/local contrast and more noise compared to the traditional retinal photograph, which makes the vessel segmentation challenging work. A hybrid algorithm is proposed to efficiently solve these problems by fusing several designed methods, taking the advantages of each method and reducing the error measurements. The algorithm has several steps consisting of image preprocessing, thresholding probe and weighted fusing. Four different methods are first designed to transform the SLO image into feature response images by taking different combinations of matched filter, contrast enhancement and mathematical morphology operators. A thresholding probe algorithm is then applied on those response images to obtain four vessel maps. Weighted majority opinion is used to fuse these vessel maps and generate a final vessel map. The experimental results showed that the proposed hybrid algorithm could successfully segment the blood vessels on SLO images, by detecting the major and small vessels and suppressing the noises. The algorithm showed substantial potential in various clinical applications. The use of this method can be also extended to medical image registration based on blood vessel location.

PURPOSE: To demonstrate a new imaging method for high resolution spectral domain optical coherence tomography (SD-OCT) for small animal developmental imaging. METHODS: Wildtype zebrafish that were 24, 48, 72, and 120 h post fertilization (hpf) and nok gene mutant (48 hpf) embryos were imaged in vivo. Three additional embryos were imaged twice, once at 72 hpf and again at 120 hpf. Images of the developing eye, brain, heart, whole body, proximal yolk sac, distal yolk sac, and tail were acquired. Three-dimensional OCT data sets (501 x 180 axial scans) were obtained as well as oversampled frames (8,100 axial scans) and repeated line scans (180 repeated frames). Scan volumes ranged from 750 x 750 microm to 3 x 3 mm, each 1.8 mm thick. Three-dimensional data sets allowed construction of C-mode slabs of the embryo. RESULTS: SD-OCT provided ultra-high resolution visualization of the eye, brain, heart, ear, and spine of the developing embryo as early as 24 hpf, and allowed development to be documented in each of these organ systems in consecutive sessions. Repeated line scanning with averaging optimized the visualization of static and dynamic structures contained in SD-OCT images. Structural defects caused by a mutation in the nok gene were readily observed as impeded ocular development, and enlarged pericardial cavities. CONCLUSIONS: SD-OCT allowed noninvasive, in vivo, ultra-high resolution, high-speed imaging of zebrafish embryos in their native state. The ability to measure structural and functional features repeatedly on the same specimen, without the need to sacrifice, promises to be a powerful tool in small animal developmental imaging.

PURPOSE: Optical coherence tomography (OCT) is a rapidly evolving, robust technology that has profoundly changed the practice of ophthalmology. Spectral domain OCT (SD-OCT) increases axial resolution 2- to 3-fold and scan speed 60- to 110-fold vs time domain OCT (TD-OCT). SD-OCT enables novel scanning, denser sampling, and 3-dimensional imaging. This thesis tests my hypothesis that SD-OCT improves reproducibility, sensitivity, and specificity for glaucoma detection. METHODS: OCT progress is reviewed from invention onward, and future development is discussed. To test the hypothesis, TD-OCT and SD-OCT reproducibility and glaucoma discrimination are evaluated. Forty-one eyes of 21 subjects (SD-OCT) and 21 eyes of 21 subjects (TD-OCT) are studied to test retinal nerve fiber layer (RNFL) thickness measurement reproducibility. Forty eyes of 20 subjects (SD-OCT) and 21 eyes of 21 subjects (TD-OCT) are investigated to test macular parameter reproducibility. For both TD-OCT and SD-OCT, 83 eyes of 83 subjects are assessed to evaluate RNFL thickness and 74 eyes of 74 subjects to evaluate macular glaucoma discrimination. RESULTS: Compared to conventional TD-OCT, SD-OCT had statistically significantly better reproducibility in most sectoral macular thickness and peripapillary RNFL sectoral measurements. There was no statistically significant difference in overall mean macular or RNFL reproducibility, or between TD-OCT and SD-OCT glaucoma discrimination. Surprisingly, TD-OCT macular RNFL thickness showed glaucoma discrimination superior to SD-OCT. CONCLUSIONS: At its current development state, SD-OCT shows better reproducibility than TD-OCT, but glaucoma discrimination is similar for TD-OCT and SD-OCT. Technological improvements are likely to enhance SD-OCT reproducibility, sensitivity, specificity, and utility, but these will require additional development.

PURPOSE: To determine the effects of age, optic disc area, ethnicity, eye, gender, and axial length on the retinal nerve fiber layer (RNFL) in the normal human eye as measured by Stratus OCT (optical coherence tomography). DESIGN: Cross-sectional observational study. PARTICIPANTS: Three hundred twenty-eight normal subjects 18 to 85 years old. METHODS: Peripapillary Fast RNFL scans performed by Stratus OCT with a nominal diameter of 3.46 mm centered on the optic disc were performed on one randomly selected eye of each subject. MAIN OUTCOME MEASURES: Linear regression analysis of the effects of age, ethnicity, gender, eye, axial length, and optic disc area on peripapillary RNFL thickness. RESULTS: The mean RNFL thickness for the entire population was 100.1 microm (standard deviation, 11.6). Thinner RNFL measurements were associated with older age (P<0.001); being Caucasian, versus being either Hispanic or Asian (P = 0.006); greater axial length (P<0.001); or smaller optic disc area (P = 0.010). For every decade of increased age, mean RNFL thickness measured thinner by approximately 2.0 microm (95% confidence interval [CI], 1.2-2.8). For every 1-mm-greater axial length, mean RNFL thickness measured thinner by approximately 2.2 microm (95% CI, 1.1-3.4). For every increase in square millimeter of optic disc area, mean RNFL thickness increased by approximately 3.3 microm (95% CI, 0.6-5.6). Comparisons between ethnic groups revealed that Caucasians had mean RNFL values (98.1+/-10.9 microm) slightly thinner than those of Hispanics (103.7+/-11.6 microm; P = 0.022) or Asians (105.8+/-9.2 microm; P = 0.043). There was no relationship between RNFL thickness and eye or gender. CONCLUSIONS: Retinal nerve fiber layer thickness, as measured by Stratus OCT, varies significantly with age, ethnicity, axial length, and optic disc area. These variables may need to be taken into account when evaluating patients for diagnosis and follow-up of glaucoma, particularly at the lower boundary of the normal range. Due to the relatively small numbers of subjects of Asian and African descent in the normative database, conclusions regarding the effect of ethnicity should be interpreted with caution.

OBJECTIVE: To evaluate the current published literature on the use of optic nerve head (ONH) and retinal nerve fiber layer (RNFL) measurement devices in diagnosing open-angle glaucoma and detecting progression. METHODS: A search of peer-reviewed literature was conducted on February 15, 2006 in PubMed and the Cochrane Library for the period January 2003 to February 2006. The search was limited to studies of adults in English-language journals and yielded 442 citations. The panel reviewed the abstracts of these articles and selected 159 articles of possible clinical relevance for review. Of these 159 full-text articles, 82 were determined to be relevant for the first author and methodologist to review and rate according to the quality of evidence. RESULTS: There were no studies classified as having the highest level of evidence (level I). The ONH and RNFL imaging instruments reviewed in this assessment were determined to be highly effective in distinguishing eyes with glaucomatous visual field (VF) loss from normal eyes without VF loss, based on level II evidence. In addition, some studies demonstrated that parameters from ONH or RNFL imaging predicted the development of VF defects among glaucoma suspects. Studies on detecting glaucoma progression showed that although there was often agreement on progression between the structural and functional (VF) tests, a significant proportion of glaucoma patients progressed by either the structural or the functional test alone. CONCLUSIONS: The ONH and RNFL imaging devices provide quantitative information for the clinician. Based on studies that have compared the various available technologies directly, there is no single imaging device that outperforms the others in distinguishing patients with glaucoma from controls. Ongoing advances in imaging and related software, as well as the impracticalities associated with obtaining and assessing optic nerve stereophotographs, have made imaging increasingly important in many practice settings. The information obtained from imaging devices is useful in clinical practice when analyzed in conjunction with other relevant parameters that define glaucoma diagnosis and progression.

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.