-
[show abstract]
[hide abstract]
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
-
[show abstract]
[hide abstract]
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
-
[show abstract]
[hide abstract]
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. · 7.64 Impact Factor
-
[show abstract]
[hide abstract]
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
-
[show abstract]
[hide abstract]
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.
-
Mao Mao,
Frances Solivan-Timpe,
Ben R Roos,
Robert F Mullins,
Thomas A Oetting, Young H Kwon,
Peter M Brzeskiewicz,
Edwin M Stone,
Wallace L M Alward,
Michael G Anderson,
John H Fingert
[show abstract]
[hide abstract]
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. · 2.20 Impact Factor
-
Proceedings of SPIE Medical Imaging 2012: Image ProcessingProceedings of SPIE Medical Imaging 2012: Image Processing; 01/2012
-
[show abstract]
[hide abstract]
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
-
[show abstract]
[hide abstract]
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. · 2.33 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Unilateral optic nerve aplasia is a rare, nonhereditary defect associated with anterior chamber malformations and other ocular malformations. We report the case of an 8½-week-old boy with unilateral optic nerve aplasia who was diagnosed with glaucoma on presentation with corneal edema and an intraocular pressure of 36 mm Hg. The cornea edema cleared after a trabeculotomy, and subsequent fundus examination revealed optic nerve aplasia that was confirmed with magnetic resonance imaging. Intraocular pressure remained well-controlled with 7½ months of follow-up. To our knowledge, this is the first documented case of optic nerve aplasia associated with glaucoma at presentation.
Journal of AAPOS: the official publication of the American Association for Pediatric Ophthalmology and Strabismus / American Association for Pediatric Ophthalmology and Strabismus 04/2011; 15(2):200-2. · 1.07 Impact Factor
-
[show abstract]
[hide abstract]
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. · 1.98 Impact Factor
-
John H Fingert,
Alan L Robin,
Jennifer L Stone,
Ben R Roos,
Lea K Davis,
Todd E Scheetz,
Steve R Bennett,
Thomas H Wassink, Young H Kwon,
Wallace L M Alward,
Robert F Mullins,
Val C Sheffield,
Edwin M Stone
[show abstract]
[hide abstract]
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. · 7.64 Impact Factor
-
Lea K Davis,
Kacie J Meyer,
Emily I Schindler,
John S Beck,
Danielle S Rudd,
A Jason Grundstad,
Todd E Scheetz,
Terry A Braun,
John H Fingert,
Wallace L M Alward, Young H Kwon,
James C Folk,
Stephen R Russell,
Thomas H Wassink,
Val C Sheffield,
Edwin M Stone
[show abstract]
[hide abstract]
ABSTRACT: This study sought to investigate the role of rare copy number variation (CNV) in age-related disorders of blindness, with a focus on primary open-angle glaucoma (POAG). Data are reported from a whole-genome copy number screen in a large cohort of 400 individuals with POAG and 500 age-matched glaucoma-free subjects.
DNA samples from patients and controls were tested for CNVs using a combination of two microarray platforms. The signal intensity data generated from these arrays were then analyzed with multiple CNV detection programs including CNAG version 2.0, PennCNV, and dChip.
A total of 11 validated CNVs were identified as recurrent in the POAG set and absent in the age-matched control set. This set included CNVs on 5q23.1 (DMXL1, DTWD2), 20p12 (PAK7), 12q14 (C12orf56, XPOT, TBK1, and RASSF3), 12p13.33 (TULP3), and 10q34.21 (PAX2), among others. The CNVs presented here are exceedingly rare and are not found in the Database of Genomic Variants. Moreover, expression data from ocular tissue support the role of these CNV-implicated genes in vision-related processes. In addition, CNV locations of DMXL1 and PAK7 overlap previously identified linkage signals for glaucoma on 5p23.1 and 20p12, respectively.
The data are consistent with the hypothesis that rare CNV plays a role in the development of POAG.
Investigative ophthalmology & visual science 02/2011; 52(10):7122-33. · 3.43 Impact Factor
-
IEEE Trans. Pattern Anal. Mach. Intell. 01/2011; 33:2245-2258.
-
Medical Image Analysis. 01/2011; 15:35-44.
-
[show abstract]
[hide abstract]
ABSTRACT: To determine the role of the recently discovered primary open angle glaucoma (POAG) risk factor mapped to chromosome 7q31 in glaucoma patients from Iowa and to determine the expression pattern of genes in the locus in human eyes.
A cohort of 545 POAG patients and 297 control subjects from Iowa were genotyped with a single nucleotide polymorphism (SNP; rs4236601) in the chromosome 7q31 locus using a quantitative polymerase chain reaction (PCR) assay. The expression of genes within the 7q31 locus, caveolin-1 (CAV1) and caveolin-2 (CAV2) in human eyes was investigated with immunohistochemistry.
The minor allele frequency (MAF) of rs4236601 was 27% in control subjects and 29% in POAG patients. We detected no statistical difference when we compared the allele frequencies of rs4236601 between POAG patients and control subjects (p=0.5). Similarly, we detected no statistical difference in the frequency of the three possible rs4236601 genotypes between patients and controls (p=0.22). Immunohistochemistry showed caveolin expression in human retina, ciliary muscle, trabecular meshwork, and Schlemm's canal. In our small cohort of donor eyes, the genotype of rs4236601 did not obviously influence labeling intensity or distribution of CAV1 and CAV2 in the retina.
A genome-wide association study of subjects from Iceland mapped the first common genetic risk factor for POAG to a small region of the genome on chromosome 7q31 that contains the caveolin genes CAV1 and CAV2. We were unable to detect this association in our patients from Iowa, suggesting that this risk factor may not have a strong effect in all populations.
Molecular vision 01/2011; 17:430-5. · 2.20 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To develop an automated approach for segmenting the neural canal opening (NCO) and cup at the level of the retinal pigment epithelium (RPE)/Bruch's membrane (BM) complex in spectral-domain optical coherence tomography (SD-OCT) volumes. To investigate the correspondence and discrepancy between the NCO-based metrics and the clinical disc margin on fundus photographs of glaucoma subjects.
SD-OCT scans and corresponding stereo fundus photographs of the optic nerve head were obtained from 68 eyes of 34 patients with glaucoma or glaucoma suspicion. Manual planimetry was performed by three glaucoma experts to delineate a reference standard (RS) for cup and disc margins from the images. An automated graph-theoretic approach was used to identify the NCO and cup. NCO-based metrics were compared with the RS.
Compared with the RS disc margin, the authors found mean unsigned and signed border differences of 2.81 ± 1.48 pixels (0.084 ± 0.044 mm) and -0.99 ± 2.02 pixels (-0.030 ± 0.061 mm), respectively, for NCO segmentation. The correlations of the linear cup-to-disc (NCO) area ratio, disc (NCO) area, rim area, and cup area of the algorithm with the RS were 0.85, 0.77, 0.69, and 0.83, respectively.
In most eyes, the NCO-based 2D metrics, as estimated by the novel automated graph-theoretic approach to segment the NCO and cup at the level of the RPE/BM complex in SD-OCT volumes, correlate well with RS. However, a small discrepancy exists in NCO-based anatomic structures and the clinical disc margin of the RS in some eyes.
Investigative ophthalmology & visual science 11/2010; 51(11):5708-17. · 3.43 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Discovery and description of heritable optic nerve head (ONH) phenotypes have been haphazard. In this preliminary study, the authors test the hypothesis that inheritable phenotypes can be discovered and quantified computationally by estimating three-dimensional ONH shape parameters from stereo color photographs from the Twins Eye Study in Tasmania and determining how much of the variability in ONH shape is accounted for by genetic influence.
Three-dimensional ONH shape was estimated by an automated algorithm from stereoscopic optic disc color photographs of a random sample of 172 subjects (344 eyes, 45 pairs of monozygotic [MZ] and 41 dizygotic [DZ] twins). Shape resemblances between eyes were quantified with a distance metric. The heritability of the shape resemblance was determined both through the distribution of the discongruence indices and through structural equation modeling techniques (ACE model).
Significantly different discongruence indices were found for MZ (1.0286; 95% CI, 0.9872-1.0701) and DZ twins (1.4218; 95% CI, 1.2631-1.5804); larger indices for DZ twins indicated that variability was substantially determined by genetic factors. The standardized variances of the A(dditive genetic), C(ommon environmental), and (nonshared) E(nvironmental) components were 0.80, 2.00 × 10(-15) and 0.20, respectively, for all OD, and 0.79, 3.24 × 10(-14), and 0.21 for all OS.
This preliminary study shows that quantitative phenotyping of the ONH shape from color images leads to phenotypes that can be measured and are largely under genetic control. The association of these inherited phenotypes with genotypes deserves confirmation and further study.
Investigative ophthalmology & visual science 11/2010; 51(11):5870-7. · 3.43 Impact Factor
-
Kacie J Meyer,
Lea K Davis,
Emily I Schindler,
John S Beck,
Danielle S Rudd,
A Jason Grundstad,
Todd E Scheetz,
Terry A Braun,
John H Fingert,
Wallace L Alward, Young H Kwon,
James C Folk,
Stephen R Russell,
Thomas H Wassink,
Edwin M Stone,
Val C Sheffield
[show abstract]
[hide abstract]
ABSTRACT: Age-related macular degeneration (AMD) is a complex genetic disease, with many loci demonstrating appreciable attributable disease risk. Despite significant progress toward understanding the genetic and environmental etiology of AMD, identification of additional risk factors is necessary to fully appreciate and treat AMD pathology. In this study, we investigated copy number variants (CNVs) as potential AMD risk variants in a cohort of 400 AMD patients and 500 AMD-free controls ascertained at the University of Iowa. We used three publicly available copy number programs to analyze signal intensity data from Affymetrix GeneChip SNP Microarrays. CNVs were ranked based on prevalence in the disease cohort and absence from the control group; high interest CNVs were subsequently confirmed by qPCR. While we did not observe a single-locus "risk CNV" that could account for a major fraction of AMD, we identified several rare and overlapping CNVs containing or flanking compelling candidate genes such as NPHP1 and EFEMP1. These and other candidate genes highlighted by this study deserve further scrutiny as sources of genetic risk for AMD.
Human Genetics 10/2010; 129(1):91-100. · 5.07 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To determine the prevalence and risk factors for escalation of glaucoma therapy after deep lamellar endothelial keratoplasty (DLEK).
Retrospective review of every case of DLEK performed at a tertiary care facility between December 1, 2003 and January 31, 2006.
Eighty eyes met the inclusion criteria. Escalation of glaucoma therapy occurred in 13 eyes (16.3%) during a mean follow-up period of 27.1 months. Ten eyes required additional topical medical therapy, and 3 eyes required surgical intervention. Glaucoma therapy escalation was significantly associated with preexisting glaucoma (42.9% vs. 10.6%; P = 0.008).
Escalation of glaucoma therapy is not uncommon after DLEK, especially in eyes with preexisting glaucoma.
Cornea 09/2010; 29(9):991-5. · 1.73 Impact Factor
