Young H Kwon

University of Iowa, Iowa City, IA, United States

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Publications (73)258.87 Total impact

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    ABSTRACT: Patients with a congenital optic nerve disease, cavitary optic disc anomaly (CODA), are born with profound excavation of the optic nerve resembling glaucoma. We previously mapped the gene that causes autosomal dominant CODA in a large pedigree to a chromosome 12q locus. Using comparative genomic hybridization and quantitative PCR analysis of this pedigree, we report identifying a 6Kbp heterozygous triplication upstream of the matrix metalloproteinase 19 (MMP19) gene, present in all 17 affected family members and no normal members. Moreover, the triplication was not detected in 78 control subjects or in the Database of Genomic Variants. We further detected the same 6Kbp triplication in 1 of 24 unrelated CODA patients and in none of 172 glaucoma patients. Analysis with a luciferase assay showed that the 6Kbp sequence has transcription enhancer activity. A 773bp fragment of the 6Kbp DNA segment increased downstream gene expression 8-fold, suggesting that triplication of this sequence may lead to dysregulation of the downstream gene, MMP19, in CODA patients. Lastly, immunohistochemical analysis of human donor eyes revealed strong expression of MMP19 in optic nerve head. These data strongly suggest that triplication of an enhancer may lead to overexpression of MMP19 in the optic nerve which causes CODA.This article is protected by copyright. All rights reserved
    Human Mutation 01/2015; · 5.05 Impact Factor
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    ABSTRACT: Purpose: To determine relationships between SD-OCT derived regional damage to the retinal ganglion cell-axonal complex (RGC-AC) and visual thresholds for each location of the Humphrey 24-2 visual field, in all stages of open-angle glaucoma. Methods: Patients with early, moderate and advanced glaucoma were recruited from a tertiary glaucoma clinic. Humphrey 24-2 and 9-field Spectralis SD-OCT were acquired for each subject. Individual OCT volumes were aligned, nerve fiber (NFL), ganglion cell and inner plexiform layers (GCL+IPL) co-segmented. These layers were then partitioned into 54 sectors corresponding to the 24-2 grid. A Support Vector Machine was trained independently for each sector to predict the sector threshold, using these structural properties. Results: 122 consecutive subjects, 43 early, 39 moderate, and 40 advanced, glaucoma were included (122 eyes). Average correlation coefficient (R) was 0.68 (0.47 - 0.82), and average root mean squared error (RMSE) was 6.92dB (3.93 - 8.68dB). Prediction performance averaged over the entire field, superior hemifield and inferior hemifield had R (RMSE) values of 0.77 (3.76), 0.80 (5.05), and 0.84 (3.80) dB, respectively. Conclusions: Predicting individual 24-2 visual field thresholds from structural information derived from 9-field SD-OCT local NFL and GCL+IPL thicknesses using the RGC-AC concept is feasible, showing the potential for the predictive ability of SD-OCT structural information for visual function. Ultimately, it may be feasible to complement and reduce the burden of subjective visual field testing in glaucoma patients with predicted function derived objectively from OCT. Copyright © 2014 by Association for Research in Vision and Ophthalmology.
    Investigative Ophthalmology &amp Visual Science 12/2014; · 3.66 Impact Factor
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    ABSTRACT: The need to segment multiple interacting surfaces is a common problem in medical imaging and it is often assumed that such surfaces are continuous within the confines of the region of interest. However, in some application areas, the surfaces of interest may contain a shared hole in which the surfaces no longer exist and the exact location of the hole boundary is not known a priori. The boundary of the neural canal opening seen in spectral-domain optical coherence tomography volumes is an example of a "hole" embedded with multiple surrounding surfaces. Segmentation approaches that rely on finding the surfaces alone are prone to failures as deeper structures within the hole can "attract" the surfaces and pull them away from their correct location at the hole boundary. With this application area in mind, we present a graph-theoretic approach for segmenting multiple surfaces with a shared hole. The overall cost function that is optimized consists of both the costs of the surfaces outside the hole and the cost of boundary of the hole itself. The constraints utilized were appropriately adapted in order to ensure the smoothness of the hole boundary in addition to ensuring the smoothness of the non-overlapping surfaces. By using this approach, a significant improvement was observed over a more traditional two-pass approach in which the surfaces are segmented first (assuming the presence of no hole) followed by segmenting the neural canal opening.
    Medical Image Computing and Computer-Assisted Intervention – MICCAI 2014; 09/2014
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    ABSTRACT: The aim of this study was to assess and compare the association of glaucoma therapy with graft survival after performing penetrating keratoplasty (PKP) and Descemet stripping automated endothelial keratoplasty (DSAEK).
    Cornea 06/2014; · 1.75 Impact Factor
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    ABSTRACT: Purpose: To compare the reproducibility of SD-OCT-based ganglion-cell-layer-plus-inner-plexiform-layer (GCL+IPL) thickness measurements for glaucoma patients obtained using both a publicly available and a commercially available algorithm. Methods: Macula SD-OCT volumes (Cirrus, Carl Zeiss Meditec, Inc., Dublin, CA, 200 x 200 x 1024 voxels, 6 x 6 x 2 mm(3)) were obtained prospectively in both eyes of patients with open-angle glaucoma or glaucoma suspicion on two separate visits within four months. The combined GCL+IPL thickness was computed for each SD-OCT volume within an elliptical annulus centered at the fovea based on two algorithms: (1) a previously published graph-theoretic layer segmentation approach developed at The University of Iowa and (2) the Ganglion Cell Analysis module of version 6 of the Zeiss Cirrus software. The mean overall thickness in the elliptical annulus was computed as well as the thickness within six sectors. For statistical analyses, eyes with an SD-OCT volume with a low signal strength (< 6), image acquisition errors, or errors in performing the commercial GCL+IPL analysis in at least one of the repeat acquisitions were excluded. Results: Using 104 eyes (from 56 patients) with repeated measurements, the intraclass correlation coefficient for the overall elliptical annular GCL+IPL thickness was 0.98 (95% CI: 0.97-0.99) using the Iowa algorithm and 0.95 (95% CI: 0.93-0.97) using the Cirrus algorithm; the intervisit standard deviation was 1.55 µm (Iowa) and 2.45 µm (Cirrus); and the coefficient of variation was 2.2% (Iowa) and 3.5% (Cirrus), p < 0.0001. Conclusions: SD-OCT-based GCL+IPL thickness measurements in early glaucoma patients are highly reproducible.
    Investigative ophthalmology & visual science 09/2013; · 3.43 Impact Factor
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    ABSTRACT: To report an automated method for adjustment of the retinal angle in spectral-domain optical coherence tomography (SD-OCT) and compare its intervisit reproducibility of the peripapillary retinal nerve fiber layer (RNFL) thicknesses of glaucomatous eyes to that obtained by the Cirrus algorithm. Methods: Fifty-six glaucoma and glaucoma suspect subjects were repeatedly imaged, and optic nerve head (ONH)-centered OCT image volumes (200 × 200 × 1024 voxels, 6 × 6 × 2 mm3, CirrusTM HD-OCT machine (Carl Zeiss Meditec, Inc., Dublin, CA)) were acquired within a 4-month period from one eye of the 56 patients. Retinal angle correction in B-scans was accomplished by adjusting the angle using the voxel aspect ratio of the SD-OCT followed by straightening of rotated A-scans. The RNFL layer was automatically segmented using the Iowa Reference Algorithm. Reproducibility of the peripapillary RNFL thicknesses was determined by intraclass correlation coefficient (ICC), coefficient of variation (CV), repeatability coefficient (RC), and 95% tolerance limit (TL) for the Iowa Reference Algorithm without and with the retinal angle correction and for the Cirrus algorithm (Cirrus version Results: The angle corrected Iowa Reference Algorithm (ICC: 0.990, 95% confidence interval (CI): 0.983 - 0.994) for peripapillary RNFL thicknesses showed significantly better reproducibility than the non-angle corrected algorithm (ICC: 0.964, 95% CI: 0.940 - 0.979) and the Cirrus algorithm (ICC: 0.960, 95% CI: 0.933 - 0.976) based on the 95% CIs for the ICCs. Conclusions: Angle correction leads to more consistent peripapillary RNFL thicknesses. This may lead to improved management of patients with glaucoma.
    Investigative ophthalmology & visual science 06/2013; · 3.43 Impact Factor
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    ABSTRACT: Glaucoma is one of the major causes of blindness worldwide. One important structural parameter for the diagnosis and management of glaucoma is the cup-to-disc ratio (CDR), which tends to become larger as glaucoma progresses. While approaches exist for segmenting the optic disc and cup within fundus photographs, and more recently, within spectral-domain optical coherence tomography (SD-OCT) volumes, no approaches have been reported for the simultaneous segmentation of these structures within both modalities combined. In this work, a multimodal pixel-classification approach for the segmentation of the optic disc and cup within fundus photographs and SD-OCT volumes is presented. In particular, after segmentation of other important structures (such as the retinal layers and retinal blood vessels) and fundus-to-SD-OCT image registration, features are extracted from both modalities and a k-nearest-neighbor classification approach is used to classify each pixel as cup, rim, or background. The approach is evaluated on 70 multimodal image pairs from 35 subjects in a leave-10%-out fashion (by subject). A significant improvement in classification accuracy is obtained using the multimodal approach over that obtained from the corresponding unimodal approach (97.8% versus 95.2%; p < 0:05; paired t-test).
    Proc SPIE 03/2013;
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    ABSTRACT: Abstract Purpose: Copy number variations (duplications) of TANK binding kinase 1 (TBK1) have been associated with normal tension glaucoma (NTG), a common cause of blindness worldwide. Mutations in other genes involved in autophagy (TLR4 and OPTN) have been associated with NTG. Here we report searching for additional proteins involved in autophagy that may also have roles in NTG. Materials and methods: HEK-293T cells were transfected to produce synthetic TBK1 protein with FLAG and S tags. Proteins that associate with TBK1 were isolated from HEK-293T lysates using tandem affinity purification (TAP) and polyacrylamide gel electrophoresis (PAGE). Isolated proteins were identified with mass spectrometry. A cohort of 148 NTG patients and 77 controls from Iowa were tested for glaucoma-causing mutations in genes that encode identified proteins that interact with TBK1 using high resolution melt (HRM) analysis and DNA sequencing. Results: TAP studies show that three proteins expressed in HEK-293T cells (NAP1, TANK and TBKBP1) interact with TBK1. Testing cohorts of NTG and normal controls for disease-causing mutations in TANK, identified a total of nine unique variants including three non-synonymous changes, one synonymous changes and five intronic changes. When analyzed alone or as a group, the non-synonymous TBK1 coding sequence changes were not associated with either NTG or primary open angle glaucoma. Conclusion: TAP showed that NAP1, TANK and TBKBP1 interact with TBK1 and are good candidates for contributing to NTG. A mutation screen of TANK detected three non-synonymous variants. Although, it remains possible that one or more of these TANK mutations may have a role in NTG, the data in this report do not provide statistical support for an association between TANK variants and NTG.
    Current eye research 01/2013; · 1.51 Impact Factor
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    ABSTRACT: Optical coherence tomography is routinely used clinically for the detection and management of ocular diseases as well as in research where the studies may involve animals. This routine use requires that the developed automated segmentation methods not only be accurate and reliable, but also be adaptable to meet new requirements. We have previously proposed the use of a graph-theoretic approach for the automated 3-D segmentation of multiple retinal surfaces in volumetric human SD-OCT scans. The method ensures the global optimality of the set of surfaces with respect to a cost function. Cost functions have thus far been typically designed by hand by domain experts. This difficult and time-consuming task significantly impacts the adaptability of these methods to new models. Here, we describe a framework for the automated machine-learning based design of the cost function utilized by this graph-theoretic method. The impact of the learned components on the final segmentation accuracy are statistically assessed in order to tailor the method to specific applications. This adaptability is demonstrated by utilizing the method to segment seven, ten and five retinal surfaces from SD-OCT scans obtained from humans, mice and canines, respectively. The overall unsigned border position errors observed when using the recommended configuration of the graph-theoretic method was 6.45 ± 1.87 μm, 3.35 ± 0.62 μm and 9.75 ± 3.18 μm for the human, mouse and canine set of images, respectively.
    Biomedical Optics Express 01/2013; 4(12):2712-28. · 3.50 Impact Factor
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    ABSTRACT: OBJECTIVES To test the hypothesis that the amount and distribution of glaucomatous damage along the entire retinal ganglion cell-axonal complex (RGC-AC) can be quantified and to map the RGC-AC connectivity in early glaucoma using automated image analysis of standard spectral-domain optical coherence tomography. METHODS Spectral-domain optical coherence tomography volumes were obtained from 116 eyes in 58 consecutive patients with glaucoma or suspected glaucoma. Layer and optic nerve head (ONH) analysis was performed; the mean regional retinal ganglion cell layer thickness (68 regions), nerve fiber layer (NFL) thickness (120 regions), and ONH rim area (12 wedge-shaped regions) were determined. Maps of RGC-AC connectivity were created using maximum correlation between regions' ganglion cell layer thickness, NFL thickness, and ONH rim area; for retinal nerve fiber bundle regions, the maximum "thickness correlation paths" were determined. RESULTS The mean (SD) NFL thickness and ganglion cell layer thickness across all macular regions were 22.5 (7.5) μm and 33.9 (8.4) μm, respectively. The mean (SD) rim area across all ONH wedge regions was 0.038 (0.004) mm2. Connectivity maps were obtained successfully and showed typical nerve fiber bundle connectivity of the RGC-AC cell body segment to the initial NFL axonal segment, of the initial to the final RGC-AC NFL axonal segments, of the final RGC-AC NFL axonal to the ONH axonal segment, and of the RGC-AC cell body segment to the ONH axonal segment. CONCLUSIONS In early glaucoma, the amount and distribution of glaucomatous damage along the entire RGC-AC can be quantified and mapped using automated image analysis of standard spectral-domain optical coherence tomography. Our findings should contribute to better detection and improved management of glaucoma.
    Archives of ophthalmology 09/2012; 130(9):1118-26. · 3.86 Impact Factor
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    ABSTRACT: Glaucoma is a common cause of visual disability and affects ∼1.6% of individuals over 40 years of age ( 1). Non-synonymous coding sequence variations in the ankyrin repeat and SOCS box containing gene 10 (ASB10) were recently associated with 6.0% of cases of primary open angle glaucoma (POAG) in patients from Oregon and Germany. We tested a cohort of POAG patients (n= 158) and normal control subjects (n= 82), both from Iowa, for ASB10 mutations. Our study had 80% power to detect a 4.9% mutation frequency in POAG patients. A total of 11 non-synonymous coding sequence mutations were detected in the cohort, but no association with POAG was detected when analyzed individually or as a group (P > 0.05). Furthermore, a survey of the National Heart, Lung, and Blood Institute's (NHLBI's) Exome Sequencing Project revealed that non-synonymous ASB10 mutations are present in the general population at a far higher frequency than the prevalence of POAG. These data suggest that non-synonymous mutations in ASB10 do not cause Mendelian forms of POAG.
    Human Molecular Genetics 07/2012; 21(20):4543-8. · 6.68 Impact Factor
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    ABSTRACT: PURPOSE:: We identified a pattern of concentric circular transillumination defects (TIDs) in a few patients with exfoliation syndrome (XFS) using an infrared detection system. This pattern of iris abnormality has also been observed in a mouse model of XFS. The objective of the current study is to determine whether concentric iris TIDs are specific to XFS and may have some diagnostic utility for identifying early cases of disease. MATERIALS AND METHODS:: A total of 68 volunteers from the University of Iowa Glaucoma Clinic with normal eyes (n=21) or diagnoses of either XFS (n=12), pigment dispersion syndrome (PDS) (n=8), or primary open-angle glaucoma (POAG) (n=27) were enrolled in the study. The irides of these subjects were each examined by 4 ophthalmologists masked to their diagnosis, using infrared videography. The presence of concentric, circular TIDs on the videos was graded as none (grade 0), possible (grade 1), definite (grade 2), or prominent (grade 3) by 4 examiners. We searched for an association between the presence of concentric bands of transillumination and the diagnosis of XFS after removing the effect of different raters was evaluated using the Cochran-Mentel-Haenszel test. We performed the same analysis for PDS and for POAG. RESULTS:: The presence of any concentric, circular iris TIDs (grades 1 to 3) was detected in a mean of 38% normal subjects, 35% POAG patients, 53% PDS patients, and 77% of XFS patients. When the frequency of concentric, circular iris transillumination (grades 1 to 3 pooled) was compared between each of the patient groups and normal controls, a significant difference was detected between XFS patients and controls (P=0.000019). No significant difference was detected between POAG and controls (P=0.64) or between PDS and controls (P=0.20). Furthermore, prominent concentric, circular iris transillumination (grade 3) was only observed in XFS. CONCLUSIONS:: Detection of concentric, circular iris TIDs with an infrared system is easy, inexpensive, rapid, and relatively specific in XFS. Future larger studies will be needed to confirm the findings of this small pilot study. Furthermore, this examination technique has the potential to help physicians to make earlier diagnoses of XFS and to better plan for future surgeries to minimize risk of complication.
    Journal of glaucoma 04/2012; · 1.74 Impact Factor
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    ABSTRACT: The purpose of this study was to determine and compare the prevalence of glaucoma therapy escalation (GTE) after penetrating keratoplasty (PKP) and Descemet's stripping automated endothelial keratoplasty (DSAEK) in eyes with a surgical indication of pseudophakic corneal edema. A retrospective review was conducted of the medical records of all patients who underwent PKP or DSAEK to treat pseudophakic corneal edema at a tertiary eye care center from January 1 2003 to December 31, 2006. Eyes that were treated with PKP from January 1, 2003 to December 31, 2004 and with DSAEK from January 1, 2005 to December 31, 2006 were included in the statistical analysis. Inclusion criteria included satisfactory preoperative control of intraocular pressure (IOP) and follow-up of at least 12 months. The main outcome measure was GTE, which was defined as a sustained requirement for escalation of topical medical therapy or the need to provide surgical intervention to maintain a satisfactory postoperative IOP. Among 54 eyes that met the inclusion criteria, GTE occurred in 7 (35.0%) of 20 eyes after PKP and in 14 (41.2%) of 34 eyes after DSAEK (P = 0.78) during a mean follow-up period of 27.6 and 28.6 months, respectively. Surgical escalation occurred in 2 (10.0%) eyes after PKP and 2 (5.9%) eyes after DSAEK (P = 0.62), and was associated with late-onset endothelial graft failure in all four eyes. Glaucoma therapy escalation is relatively common and occurs with comparable frequency in eyes with pseudophakic corneal edema after PKP and DSAEK.
    International Ophthalmology 02/2012; 32(1):9-14.
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    ABSTRACT: To correlate the thicknesses of focal regions of the macular ganglion cell layer with those of the peripapillary nerve fiber layer using spectral-domain optical coherence tomography (SD-OCT) in glaucoma subjects. Macula and optic nerve head SD-OCT volumes were obtained in 57 eyes of 57 subjects with open-angle glaucoma or glaucoma suspicion. Using a custom automated computer algorithm, the thickness of 66 macular ganglion cell layer regions and the thickness of 12 peripapillary nerve fiber layer regions were measured from registered SD-OCT volumes. The mean thickness of each ganglion cell layer region was correlated to the mean thickness of each peripapillary nerve fiber layer region across subjects. Each ganglion cell layer region was labeled with the peripapillary nerve fiber layer region with the highest correlation using a color-coded map. The resulting color-coded correlation map closely resembled the nerve fiber bundle (NFB) pattern of retinal ganglion cells. The mean r(2) value across all local macular-peripapillary correlations was 0.49 (± 0.11). When separately analyzing the 30 glaucoma subjects from the 27 glaucoma-suspect subjects, the mean r(2) value across all local macular-peripapillary correlations was significantly larger in the glaucoma group (0.56 ± 0.13 vs. 0.37 ± 0.11; P < 0.001). A two-dimensional (2-D) spatial NFB map of the retina can be developed using structure-structure relationships from SD-OCT. Such SD-OCT-based NFB maps may enhance glaucoma detection and contribute to monitoring change in the future.
    Investigative ophthalmology & visual science 01/2012; 53(1):483-9. · 3.43 Impact Factor
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    ABSTRACT: While efficient graph-theoretic approaches exist for the optimal (with respect to a cost function) and simultaneous segmentation of multiple surfaces within volumetric medical images, the appropriate design of cost functions remains an important challenge. Previously proposed methods have used simple cost functions or optimized a combination of the same, but little has been done to design cost functions using learned features from a training set, in a less biased fashion. Here, we present a method to design cost functions for the simultaneous segmentation of multiple surfaces using the graph-theoretic approach. Classified texture features were used to create probability maps, which were incorporated into the graph-search approach. The efficiency of such an approach was tested on 10 optic nerve head centered optical coherence tomography (OCT) volumes obtained from 10 subjects that presented with glaucoma. The mean unsigned border position error was computed with respect to the average of manual tracings from two independent observers and compared to our previously reported results. A significant improvement was noted in the overall means which reduced from 9.25 +/- 4.03μm to 6.73 +/- 2.45μm (p < 0.01) and is also comparable with the inter-observer variability of 8.85 +/- 3.85μm.
    Proceedings of SPIE Medical Imaging 2012: Image ProcessingProceedings of SPIE Medical Imaging 2012: Image Processing; 01/2012
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    ABSTRACT: Analysis of mutant mouse strains and linkage analysis with human families have both demonstrated that mutations influencing the podosomal adaptor protein SH3 and PX domains 2B (SH3PXD2B) can result in a congenital form of glaucoma. Here, we use immunohistochemistry to describe localization of the SH3PXD2B protein throughout the adult human eye and test whether sequence variants in SH3PXD2B occur in multiple other forms of glaucoma. In immunohistochemical experiments, cryosections of human donor eyes were evaluated for SH3PXD2B immunoreactivity with a polyclonal antibody. In genetic experiments, exon sequences of SH3PXD2B from patients with primary congenital glaucoma (n=21), Axenfeld-Rieger syndrome (n=30), and primary open angle glaucoma (n=127) were compared to control subjects (n=89). The frequency of non-synonymous SH3PXD2B coding sequence variants were compared between patient cohorts and controls using Fisher's exact test. Varying intensities of SH3PXD2B immunoreactivity were detected in almost all ocular tissues. Among tissues important to glaucoma, immunoreactivity was detected in the drainage structures of the iridocorneal angle, ciliary body, and retinal ganglion cells. Intense immunoreactivity was present in photoreceptor inner segments. From DNA analysis, a total of 11 non-synonymous variants were detected. By Fisher's Exact test, there was not a significant skew in the overall frequency of these changes in any patient cohort versus controls (p-value >0.05). Each cohort contained unique variants not detected in other cohorts or patients. SH3PXD2B is widely distributed in the adult human eye, including several tissues important to glaucoma pathogenesis. Analysis of DNA variants in three forms of glaucoma detected multiple variants unique to each patient cohort. While statistical analysis failed to support a pathogenic role for these variants, some of them may be rare disease-causing variants whose biologic significance warrants investigation in follow up replication studies and functional assays.
    Molecular vision 01/2012; 18:705-13. · 2.25 Impact Factor
  • IEEE Transactions on Pattern Analysis and Machine Intelligence 11/2011; 33(11):2245-2258. · 5.69 Impact Factor
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    ABSTRACT: The 3-D spectral-domain optical coherence tomography (SD-OCT) images of the retina often do not reflect the true shape of the retina and are distorted differently along the x and y axes. In this paper, we propose a novel technique that uses thin-plate splines in two stages to estimate and correct the distinct axial artifacts in SD-OCT images. The method was quantitatively validated using nine pairs of OCT scans obtained with orthogonal fast-scanning axes, where a segmented surface was compared after both datasets had been corrected. The mean unsigned difference computed between the locations of this artifact-corrected surface after the single-spline and dual-spline correction was 23.36 ± 4.04 μm and 5.94 ± 1.09 μm, respectively, and showed a significant difference (p < 0.001 from two-tailed paired t-test). The method was also validated using depth maps constructed from stereo fundus photographs of the optic nerve head, which were compared to the flattened top surface from the OCT datasets. Significant differences (p < 0.001) were noted between the artifact-corrected datasets and the original datasets, where the mean unsigned differences computed over 30 optic-nerve-head-centered scans (in normalized units) were 0.134 ± 0.035 and 0.302 ± 0.134, respectively.
    Biomedical Optics Express 08/2011; 2(8):2403-16. · 3.50 Impact Factor
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    ABSTRACT: A robust multiscale stereo matching algorithm is proposed to find reliable correspondences between low contrast and weakly textured retinal image pairs with radiometric differences. Existing algorithms designed to deal with piecewise planar surfaces with distinct features and Lambertian reflectance do not apply in applications such as 3D reconstruction of medical images including stereo retinal images. In this paper, robust pixel feature vectors are formulated to extract discriminative features in the presence of noise in scale space, through which the response of low-frequency mechanisms alter and interact with the response of high-frequency mechanisms. The deep structures of the scene are represented with the evolution of disparity estimates in scale space, which distributes the matching ambiguity along the scale dimension to obtain globally coherent reconstructions. The performance is verified both qualitatively by face validity and quantitatively on our collection of stereo fundus image sets with ground truth, which have been made publicly available as an extension of standard test images for performance evaluation.
    IEEE Transactions on Software Engineering 03/2011; 33(11):2245-58. · 2.29 Impact Factor
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    ABSTRACT: We report identification of a novel genetic locus (GLC1P) for normal tension glaucoma (NTG) on chromosome 12q14 using linkage studies of an African-American pedigree (maximum non-parametric linkage score = 19.7, max LOD score = 2.7). Subsequent comparative genomic hybridization and quantitative polymerase chain reaction (PCR) experiments identified a 780 kbp duplication within the GLC1P locus that is co-inherited with NTG in the pedigree. Real-time PCR studies showed that the genes within this duplication [TBK1 (TANK-binding kinase 1), XPOT, RASSF3 and GNS] are all expressed in the human retina. Cohorts of 478 glaucoma patients (including 152 NTG patients), 100 normal control subjects and 400 age-related macular degeneration patients were subsequently tested for copy number variation in GLC1P. Overlapping duplications were detected in 2 (1.3%) of the 152 NTG subjects, one of which had a strong family history of glaucoma. These duplications defined a 300 kbp critical region of GLC1P that spans two genes (TBK1 and XPOT). Microarray expression experiments and northern blot analysis using RNA obtained from human skin fibroblast cells showed that duplication of chromosome 12q14 results in increased TBK1 and GNS transcription. Finally, immunohistochemistry studies showed that TBK1 is expressed in the ganglion cells, nerve fiber layer and microvasculature of the human retina. Together, these data link the duplication of genes on chromosome 12q14 with familial NTG and suggest that an extra copy of the encompassed TBK1 gene is likely responsible for these cases of glaucoma. However, animal studies will be necessary to rule out a role for the other duplicated or neighboring genes.
    Human Molecular Genetics 03/2011; 20(12):2482-94. · 6.68 Impact Factor

Publication Stats

2k Citations
258.87 Total Impact Points


  • 2000–2013
    • University of Iowa
      • Department of Ophthalmology and Visual Sciences
      Iowa City, IA, United States
  • 2011
    • University of Illinois at Chicago
      • Department of Psychiatry (Chicago)
      Chicago, IL, United States
  • 2002–2010
    • Iowa State University
      • • Department of Veterinary Clinical Sciences
      • • Department of Genetics, Development and Cell Biology
      • • Department of Biomedical Sciences
      Ames, IA, United States
  • 2003
    • Howard Hughes Medical Institute
      Ashburn, Virginia, United States