Faculty Bibliography

AIMS: To assess performance of classifiers trained on Heidelberg Retina Tomograph 3 (HRT3) parameters for discriminating between healthy and glaucomatous eyes. METHODS: Classifiers were trained using HRT3 parameters from 60 healthy subjects and 140 glaucomatous subjects. The classifiers were trained on all 95 variables and smaller sets created with backward elimination. Seven types of classifiers, including Support Vector Machines with radial basis (SVM-radial), and Recursive Partitioning and Regression Trees (RPART), were trained on the parameters. The area under the ROC curve (AUC) was calculated for classifiers, individual parameters and HRT3 glaucoma probability scores (GPS). Classifier AUCs and leave-one-out accuracy were compared with the highest individual parameter and GPS AUCs and accuracies. RESULTS: The highest AUC and accuracy for an individual parameter were 0.848 and 0.79, for vertical cup/disc ratio (vC/D). For GPS, global GPS performed best with AUC 0.829 and accuracy 0.78. SVM-radial with all parameters showed significant improvement over global GPS and vC/D with AUC 0.916 and accuracy 0.85. RPART with all parameters provided significant improvement over global GPS with AUC 0.899 and significant improvement over global GPS and vC/D with accuracy 0.875. CONCLUSIONS: Machine learning classifiers of HRT3 data provide significant enhancement over current methods for detection of glaucoma.

Intravitreal triamcinolone acetonide is effective in treating various ocular disorders associated with inflammation and swelling of the retina. Unfortunately, the use of intraocular steroids is also associated with several side effects, including increased intraocular pressure and the development of cataracts. This article describes a case of intravitreal steroid injection resulting in filtering bleb rupture due to an acute rise of intraocular pressure, expands on the mechanism, and provides possible ways to avoid such an occurrence in thin, cystic filtering blebs.

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.

PURPOSE: To compare stereometric parameters and classification results from the Heidelberg Retina Tomograph version 2 (HRT2); HRT3; and HRT3 Glaucoma Probability Score (GPS), an automated method of obtaining optic nerve head analysis without the need for manual definition of disc margin. DESIGN: Retrospective cross-sectional study. PARTICIPANTS: Five hundred four eyes from 281 consecutive subjects (glaucoma, glaucoma suspect, and healthy) evaluated in a glaucoma clinic. METHODS: All participants had HRT2 scanning of the optic nerve head. Inclusion criteria were scans with good centration and focus, even illumination, an overall quality score by HRT3 of acceptable or better, and standard deviation < 50 mum. A Bland-Altman analysis was used for the comparison of HRT2 and HRT3. From these results, calibration equations were determined to permit conversion of the measurements between devices. The agreement between HRT2 and HRT3 Moorfields regression analysis (MRA) and HRT3 GPS classification methods was measured using kappa statistics. MAIN OUTCOME MEASURES: Heidelberg Retina Tomograph version 2 and HRT3 stereometric parameters, MRA, and global GPS. RESULTS: There was a statistically significant difference between HRT2 and HRT3 global disc area, rim area, cup area, rim volume, cup volume, height variation contour, and retinal nerve fiber layer cross-sectional area stereometric parameters. All of those parameters were smaller using HRT3, due to a manufacturer-reported horizontal scaling error of 4% in HRT2 that was corrected in HRT3. kappas for agreement were 0.60 between classifications (within normal limits, borderline, and outside normal limits) of MRA by HRT2 and HRT3 and 0.47 between HRT3 MRA and GPS. CONCLUSIONS: The HRT3 generally provided smaller stereometric disc measurements than HRT2. There was no clear conversion between HRT3 and GPS parameters, as the 2 methods for measuring the stereometric parameters differ.

Two patients who underwent trabeculectomy and postoperatively manifested axially shallow anterior chamber associated with hypotony but without choroidal effusion are described. The first patient was treated conservatively with topical cycloplegics. The second patient was treated with pars plana anterior vitrectomy. The interventions resulted in deepening of the anterior chamber and posterior rotation of the ciliary body to a natural position as observed by ultrasound biomicroscopy. Intraocular pressure remained low in both cases. These cases demonstrate that hypotony and axial shallowing of the anterior chamber after trabeculectomy can result in a malignant glaucoma-like appearance.

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.