New diagnostics for melanoma detection: from artificial intelligence to RNA microarrays.

PubMed

Ahlgrimm-Siess, Verena; Laimer, Martin; Arzberger, Edith; Hofmann-Wellenhof, Rainer

2012-07-01

Early detection of melanoma remains crucial to ensuring a favorable prognosis. Dermoscopy and total body photography are well-established noninvasive aids that increase the diagnostic accuracy of dermatologists in their daily routine, beyond that of a naked-eye examination. New noninvasive diagnostic techniques, such as reflectance confocal microscopy, multispectral digital imaging and RNA microarrays, are currently being investigated to determine their utility for melanoma detection. This review presents emerging technologies for noninvasive melanoma diagnosis, and discusses their advantages and limitations.

Microarray expression profiling in adhesion and normal peritoneal tissues.

PubMed

Ambler, Dana R; Golden, Alicia M; Gell, Jennifer S; Saed, Ghassan M; Carey, David J; Diamond, Michael P

2012-05-01

To identify molecular markers associated with adhesion and normal peritoneal tissue using microarray expression profiling. Comparative study. University hospital. Five premenopausal women. Adhesion and normal peritoneal tissue samples were obtained from premenopausal women. Ribonucleic acid was extracted using standard protocols and processed for hybridization to Affymetrix Whole Transcript Human Gene Expression Chips. Microarray data were obtained from five different patients, each with adhesion tissue and normal peritoneal samples. Real-time polymerase chain reaction was performed for confirmation using standard protocols. Gene expression in postoperative adhesion and normal peritoneal tissues. A total of 1,263 genes were differentially expressed between adhesion and normal tissues. One hundred seventy-three genes were found to be up-regulated and 56 genes were down-regulated in the adhesion tissues compared with normal peritoneal tissues. The genes were sorted into functional categories according to Gene Ontology annotations. Twenty-six up-regulated genes and 11 down-regulated genes were identified with functions potentially relevant to the pathophysiology of postoperative adhesions. We evaluated and confirmed expression of 12 of these specific genes via polymerase chain reaction. The pathogenesis, natural history, and optimal treatment of postoperative adhesive disease remains unanswered. Microarray analysis of adhesions identified specific genes with increased and decreased expression when compared with normal peritoneum. Knowledge of these genes and ontologic pathways with altered expression provide targets for new therapies to treat patients who have or are at risk for postoperative adhesions. Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

A New Modified Histogram Matching Normalization for Time Series Microarray Analysis.

PubMed

Astola, Laura; Molenaar, Jaap

2014-07-01

Microarray data is often utilized in inferring regulatory networks. Quantile normalization (QN) is a popular method to reduce array-to-array variation. We show that in the context of time series measurements QN may not be the best choice for this task, especially not if the inference is based on continuous time ODE model. We propose an alternative normalization method that is better suited for network inference from time series data.

Microarray analysis of the rat lacrimal gland following the loss of parasympathetic control of secretion

PubMed Central

Nguyen, Doan H.; Toshida, Hiroshi; Schurr, Jill; Beuerman, Roger W.

2010-01-01

Previous studies showed that loss of muscarinic parasympathetic input to the lacrimal gland (LG) leads to a dramatic reduction in tear secretion and profound changes to LG structure. In this study, we used DNA microarrays to examine the regulation of the gene expression of the genes for secretory function and organization of the LG. Long-Evans rats anesthetized with a mixture of ketamine/xylazine (80:10 mg/kg) underwent unilateral sectioning of the greater superficial petrosal nerve, the input to the pterygopalatine ganglion. After 7 days, tear secretion was measured, the animals were killed, and structural changes in the LG were examined by light microscopy. Total RNA from control and experimental LGs (n = 5) was used for DNA microarray analysis employing the U34A GeneChip. Three statistical algorithms (detection, change call, and signal log ratio) were used to determine differential gene expression using the Microarray Suite (5.0) and Data Mining Tools (3.0). Tear secretion was significantly reduced and corneal ulcers developed in all experimental eyes. Light microscopy showed breakdown of the acinar structure of the LG. DNA microarray analysis showed downregulation of genes associated with the endoplasmic reticulum and Golgi, including genes involved in protein folding and processing. Conversely, transcripts for cytoskeleton and extracellular matrix components, inflammation, and apoptosis were upregulated. The number of significantly upregulated genes (116) was substantially greater than the number of downregulated genes (49). Removal of the main secretory input to the rat LG resulted in clinical symptoms associated with severe dry eye. Components of the secretory pathway were negatively affected, and the increase in cell proliferation and inflammation may lead to loss of organization in the parasympathectomized lacrimal gland. PMID:15084711

A New Modified Histogram Matching Normalization for Time Series Microarray Analysis

PubMed Central

Astola, Laura; Molenaar, Jaap

2014-01-01

Microarray data is often utilized in inferring regulatory networks. Quantile normalization (QN) is a popular method to reduce array-to-array variation. We show that in the context of time series measurements QN may not be the best choice for this task, especially not if the inference is based on continuous time ODE model. We propose an alternative normalization method that is better suited for network inference from time series data. PMID:27600344

Optimised laser microdissection of the human ocular surface epithelial regions for microarray studies

PubMed Central

2013-01-01

Background The most important challenge of performing insitu transcriptional profiling of the human ocular surface epithelial regions is obtaining samples in sufficient amounts, without contamination from adjacent tissue, as the region of interest is microscopic and closely apposed to other tissues regions. We have effectively collected ocular surface (OS) epithelial tissue samples from the Limbal Epithelial Crypt (LEC), limbus, cornea and conjunctiva of post-mortem cadaver eyes with laser microdissection (LMD) technique for gene expression studies with spotted oligonucleotide microarrays and Gene 1.0 ST arrays. Methods Human donor eyes (4 pairs for spotted oligonucleotide microarrays, 3 pairs for Gene 1.0 ST arrays) consented for research were included in this study with due ethical approval of the Nottingham Research Ethics Committee. Eye retrieval was performed within 36 hours of post-mortem period. The dissected corneoscleral buttons were immersed in OCT media and frozen in liquid nitrogen and stored at −80°C till further use. Microscopic tissue sections of interest were taken on PALM slides and stained with Toluidine Blue for laser microdissection with PALM microbeam systems. Optimisation of the laser microdissection technique was crucial for efficient and cost effective sample collection. Results The starting concentration of RNA as stipulated by the protocol of microarray platforms was taken as the cut-off concentration of RNA samples in our studies. The area of LMD tissue processed for spotted oligonucleotide microarray study ranged from 86,253 μm2 in LEC to 392,887 μm2 in LEC stroma. The RNA concentration of the LMD samples ranged from 22 to 92 pg/μl. The recommended starting concentration of the RNA samples used for Gene 1.0 ST arrays was 6 ng/5 μl. To achieve the desired RNA concentration the area of ocular surface epithelial tissue sample processed for the Gene 1.0 ST array experiments was approximately 100,0000 μm2 to 130,0000 μm2. RNA concentration of these samples ranged from 10.88 ng/12 μl to 25.8 ng/12 μl, with the RNA integrity numbers (RIN) for these samples from 3.3 to 7.9. RNA samples with RIN values below 2, that had failed to amplify satisfactorily were discarded. Conclusions The optimised protocol for sample collection and laser microdissection improved the RNA yield of the insitu ocular surface epithelial regions for effective microarray studies on spotted oligonucleotide and affymetrix platforms. PMID:24160452

Tomato Expression Database (TED): a suite of data presentation and analysis tools

PubMed Central

Fei, Zhangjun; Tang, Xuemei; Alba, Rob; Giovannoni, James

2006-01-01

The Tomato Expression Database (TED) includes three integrated components. The Tomato Microarray Data Warehouse serves as a central repository for raw gene expression data derived from the public tomato cDNA microarray. In addition to expression data, TED stores experimental design and array information in compliance with the MIAME guidelines and provides web interfaces for researchers to retrieve data for their own analysis and use. The Tomato Microarray Expression Database contains normalized and processed microarray data for ten time points with nine pair-wise comparisons during fruit development and ripening in a normal tomato variety and nearly isogenic single gene mutants impacting fruit development and ripening. Finally, the Tomato Digital Expression Database contains raw and normalized digital expression (EST abundance) data derived from analysis of the complete public tomato EST collection containing >150 000 ESTs derived from 27 different non-normalized EST libraries. This last component also includes tools for the comparison of tomato and Arabidopsis digital expression data. A set of query interfaces and analysis, and visualization tools have been developed and incorporated into TED, which aid users in identifying and deciphering biologically important information from our datasets. TED can be accessed at . PMID:16381976

Tomato Expression Database (TED): a suite of data presentation and analysis tools.

PubMed

Fei, Zhangjun; Tang, Xuemei; Alba, Rob; Giovannoni, James

2006-01-01

The Tomato Expression Database (TED) includes three integrated components. The Tomato Microarray Data Warehouse serves as a central repository for raw gene expression data derived from the public tomato cDNA microarray. In addition to expression data, TED stores experimental design and array information in compliance with the MIAME guidelines and provides web interfaces for researchers to retrieve data for their own analysis and use. The Tomato Microarray Expression Database contains normalized and processed microarray data for ten time points with nine pair-wise comparisons during fruit development and ripening in a normal tomato variety and nearly isogenic single gene mutants impacting fruit development and ripening. Finally, the Tomato Digital Expression Database contains raw and normalized digital expression (EST abundance) data derived from analysis of the complete public tomato EST collection containing >150,000 ESTs derived from 27 different non-normalized EST libraries. This last component also includes tools for the comparison of tomato and Arabidopsis digital expression data. A set of query interfaces and analysis, and visualization tools have been developed and incorporated into TED, which aid users in identifying and deciphering biologically important information from our datasets. TED can be accessed at http://ted.bti.cornell.edu.

A robust two-way semi-linear model for normalization of cDNA microarray data

PubMed Central

Wang, Deli; Huang, Jian; Xie, Hehuang; Manzella, Liliana; Soares, Marcelo Bento

2005-01-01

Background Normalization is a basic step in microarray data analysis. A proper normalization procedure ensures that the intensity ratios provide meaningful measures of relative expression values. Methods We propose a robust semiparametric method in a two-way semi-linear model (TW-SLM) for normalization of cDNA microarray data. This method does not make the usual assumptions underlying some of the existing methods. For example, it does not assume that: (i) the percentage of differentially expressed genes is small; or (ii) the numbers of up- and down-regulated genes are about the same, as required in the LOWESS normalization method. We conduct simulation studies to evaluate the proposed method and use a real data set from a specially designed microarray experiment to compare the performance of the proposed method with that of the LOWESS normalization approach. Results The simulation results show that the proposed method performs better than the LOWESS normalization method in terms of mean square errors for estimated gene effects. The results of analysis of the real data set also show that the proposed method yields more consistent results between the direct and the indirect comparisons and also can detect more differentially expressed genes than the LOWESS method. Conclusions Our simulation studies and the real data example indicate that the proposed robust TW-SLM method works at least as well as the LOWESS method and works better when the underlying assumptions for the LOWESS method are not satisfied. Therefore, it is a powerful alternative to the existing normalization methods. PMID:15663789

Longitudinal assessment of optical quality and intraocular scattering using the double-pass instrument in normal eyes and eyes with short tear breakup time.

PubMed

Kobashi, Hidenaga; Kamiya, Kazutaka; Yanome, Kyohei; Igarashi, Akihito; Shimizu, Kimiya

2013-01-01

To assess the longitudinal changes in optical quality including intraocular scattering in normal eyes and eyes with short tear breakup time (TBUT). We prospectively examined twenty eyes of 20 healthy subjects, and age-matched twenty eyes of 20 short TBUT subjects. The modulation transfer function (MTF) cutoff frequency, the Strehl ratio, and the objective scattering index (OSI) were quantitatively assessed using an Optical Quality Analysis System. We investigated the changes in these variables measured consecutively at the initial examination, 5, and 10 seconds without blinking. We also compared these variables in eyes with short TBUT with those in normal eyes. No significant differences in the MTF cutoff frequency, Strehl ratio, or OSI were detected over a 10-second period in normal eyes. These variables also became significantly degraded even over a 5-second period in eyes with short TBUT (p<0.01). We found significant differences in these variables at 5 and 10 seconds (p<0.05), but none immediately after the blink between normal and short TBUT eyes. Optical quality including intraocular scattering deteriorated significantly with time in eyes with short TBUT, whereas we found significant differences over a 10-second period in normal eyes. Eyes with short TBUT showed greater deterioration in optical quality after the blink than normal eyes. The longitudinal assessment of optical quality may be effective in distinguishing eyes with short TBUT from normal eyes.

WebArray: an online platform for microarray data analysis

PubMed Central

Xia, Xiaoqin; McClelland, Michael; Wang, Yipeng

2005-01-01

Background Many cutting-edge microarray analysis tools and algorithms, including commonly used limma and affy packages in Bioconductor, need sophisticated knowledge of mathematics, statistics and computer skills for implementation. Commercially available software can provide a user-friendly interface at considerable cost. To facilitate the use of these tools for microarray data analysis on an open platform we developed an online microarray data analysis platform, WebArray, for bench biologists to utilize these tools to explore data from single/dual color microarray experiments. Results The currently implemented functions were based on limma and affy package from Bioconductor, the spacings LOESS histogram (SPLOSH) method, PCA-assisted normalization method and genome mapping method. WebArray incorporates these packages and provides a user-friendly interface for accessing a wide range of key functions of limma and others, such as spot quality weight, background correction, graphical plotting, normalization, linear modeling, empirical bayes statistical analysis, false discovery rate (FDR) estimation, chromosomal mapping for genome comparison. Conclusion WebArray offers a convenient platform for bench biologists to access several cutting-edge microarray data analysis tools. The website is freely available at . It runs on a Linux server with Apache and MySQL. PMID:16371165

The statistics of identifying differentially expressed genes in Expresso and TM4: a comparison

PubMed Central

Sioson, Allan A; Mane, Shrinivasrao P; Li, Pinghua; Sha, Wei; Heath, Lenwood S; Bohnert, Hans J; Grene, Ruth

2006-01-01

Background Analysis of DNA microarray data takes as input spot intensity measurements from scanner software and returns differential expression of genes between two conditions, together with a statistical significance assessment. This process typically consists of two steps: data normalization and identification of differentially expressed genes through statistical analysis. The Expresso microarray experiment management system implements these steps with a two-stage, log-linear ANOVA mixed model technique, tailored to individual experimental designs. The complement of tools in TM4, on the other hand, is based on a number of preset design choices that limit its flexibility. In the TM4 microarray analysis suite, normalization, filter, and analysis methods form an analysis pipeline. TM4 computes integrated intensity values (IIV) from the average intensities and spot pixel counts returned by the scanner software as input to its normalization steps. By contrast, Expresso can use either IIV data or median intensity values (MIV). Here, we compare Expresso and TM4 analysis of two experiments and assess the results against qRT-PCR data. Results The Expresso analysis using MIV data consistently identifies more genes as differentially expressed, when compared to Expresso analysis with IIV data. The typical TM4 normalization and filtering pipeline corrects systematic intensity-specific bias on a per microarray basis. Subsequent statistical analysis with Expresso or a TM4 t-test can effectively identify differentially expressed genes. The best agreement with qRT-PCR data is obtained through the use of Expresso analysis and MIV data. Conclusion The results of this research are of practical value to biologists who analyze microarray data sets. The TM4 normalization and filtering pipeline corrects microarray-specific systematic bias and complements the normalization stage in Expresso analysis. The results of Expresso using MIV data have the best agreement with qRT-PCR results. In one experiment, MIV is a better choice than IIV as input to data normalization and statistical analysis methods, as it yields as greater number of statistically significant differentially expressed genes; TM4 does not support the choice of MIV input data. Overall, the more flexible and extensive statistical models of Expresso achieve more accurate analytical results, when judged by the yardstick of qRT-PCR data, in the context of an experimental design of modest complexity. PMID:16626497

Comparative study of joint analysis of microarray gene expression data in survival prediction and risk assessment of breast cancer patients

PubMed Central

2016-01-01

Abstract Microarray gene expression data sets are jointly analyzed to increase statistical power. They could either be merged together or analyzed by meta-analysis. For a given ensemble of data sets, it cannot be foreseen which of these paradigms, merging or meta-analysis, works better. In this article, three joint analysis methods, Z -score normalization, ComBat and the inverse normal method (meta-analysis) were selected for survival prognosis and risk assessment of breast cancer patients. The methods were applied to eight microarray gene expression data sets, totaling 1324 patients with two clinical endpoints, overall survival and relapse-free survival. The performance derived from the joint analysis methods was evaluated using Cox regression for survival analysis and independent validation used as bias estimation. Overall, Z -score normalization had a better performance than ComBat and meta-analysis. Higher Area Under the Receiver Operating Characteristic curve and hazard ratio were also obtained when independent validation was used as bias estimation. With a lower time and memory complexity, Z -score normalization is a simple method for joint analysis of microarray gene expression data sets. The derived findings suggest further assessment of this method in future survival prediction and cancer classification applications. PMID:26504096

Microfluidic extraction and microarray detection of biomarkers from cancer tissue slides

NASA Astrophysics Data System (ADS)

Nguyen, H. T.; Dupont, L. N.; Jean, A. M.; Géhin, T.; Chevolot, Y.; Laurenceau, E.; Gijs, M. A. M.

2018-03-01

We report here a new microfluidic method allowing for the quantification of human epidermal growth factor receptor 2 (HER2) expression levels from formalin-fixed breast cancer tissues. After partial extraction of proteins from the tissue slide, the extract is routed to an antibody (Ab) microarray for HER2 titration by fluorescence. Then the HER2-expressing cell area is evaluated by immunofluorescence (IF) staining of the tissue slide and used to normalize the fluorescent HER2 signal measured from the Ab microarray. The number of HER2 gene copies measured by fluorescence in situ hybridization (FISH) on an adjacent tissue slide is concordant with the normalized HER2 expression signal. This work is the first study implementing biomarker extraction and detection from cancer tissue slides using microfluidics in combination with a microarray system, paving the way for further developments towards multiplex and precise quantification of cancer biomarkers.

Normal uniform mixture differential gene expression detection for cDNA microarrays

PubMed Central

Dean, Nema; Raftery, Adrian E

2005-01-01

Background One of the primary tasks in analysing gene expression data is finding genes that are differentially expressed in different samples. Multiple testing issues due to the thousands of tests run make some of the more popular methods for doing this problematic. Results We propose a simple method, Normal Uniform Differential Gene Expression (NUDGE) detection for finding differentially expressed genes in cDNA microarrays. The method uses a simple univariate normal-uniform mixture model, in combination with new normalization methods for spread as well as mean that extend the lowess normalization of Dudoit, Yang, Callow and Speed (2002) [1]. It takes account of multiple testing, and gives probabilities of differential expression as part of its output. It can be applied to either single-slide or replicated experiments, and it is very fast. Three datasets are analyzed using NUDGE, and the results are compared to those given by other popular methods: unadjusted and Bonferroni-adjusted t tests, Significance Analysis of Microarrays (SAM), and Empirical Bayes for microarrays (EBarrays) with both Gamma-Gamma and Lognormal-Normal models. Conclusion The method gives a high probability of differential expression to genes known/suspected a priori to be differentially expressed and a low probability to the others. In terms of known false positives and false negatives, the method outperforms all multiple-replicate methods except for the Gamma-Gamma EBarrays method to which it offers comparable results with the added advantages of greater simplicity, speed, fewer assumptions and applicability to the single replicate case. An R package called nudge to implement the methods in this paper will be made available soon at . PMID:16011807

Genome Consortium for Active Teaching: Meeting the Goals of BIO2010

PubMed Central

Ledbetter, Mary Lee S.; Hoopes, Laura L.M.; Eckdahl, Todd T.; Heyer, Laurie J.; Rosenwald, Anne; Fowlks, Edison; Tonidandel, Scott; Bucholtz, Brooke; Gottfried, Gail

2007-01-01

The Genome Consortium for Active Teaching (GCAT) facilitates the use of modern genomics methods in undergraduate education. Initially focused on microarray technology, but with an eye toward diversification, GCAT is a community working to improve the education of tomorrow's life science professionals. GCAT participants have access to affordable microarrays, microarray scanners, free software for data analysis, and faculty workshops. Microarrays provided by GCAT have been used by 141 faculty on 134 campuses, including 21 faculty that serve large numbers of underrepresented minority students. An estimated 9480 undergraduates a year will have access to microarrays by 2009 as a direct result of GCAT faculty workshops. Gains for students include significantly improved comprehension of topics in functional genomics and increased interest in research. Faculty reported improved access to new technology and gains in understanding thanks to their involvement with GCAT. GCAT's network of supportive colleagues encourages faculty to explore genomics through student research and to learn a new and complex method with their undergraduates. GCAT is meeting important goals of BIO2010 by making research methods accessible to undergraduates, training faculty in genomics and bioinformatics, integrating mathematics into the biology curriculum, and increasing participation by underrepresented minority students. PMID:17548873

Genome Consortium for Active Teaching: meeting the goals of BIO2010.

PubMed

Campbell, A Malcolm; Ledbetter, Mary Lee S; Hoopes, Laura L M; Eckdahl, Todd T; Heyer, Laurie J; Rosenwald, Anne; Fowlks, Edison; Tonidandel, Scott; Bucholtz, Brooke; Gottfried, Gail

2007-01-01

The Genome Consortium for Active Teaching (GCAT) facilitates the use of modern genomics methods in undergraduate education. Initially focused on microarray technology, but with an eye toward diversification, GCAT is a community working to improve the education of tomorrow's life science professionals. GCAT participants have access to affordable microarrays, microarray scanners, free software for data analysis, and faculty workshops. Microarrays provided by GCAT have been used by 141 faculty on 134 campuses, including 21 faculty that serve large numbers of underrepresented minority students. An estimated 9480 undergraduates a year will have access to microarrays by 2009 as a direct result of GCAT faculty workshops. Gains for students include significantly improved comprehension of topics in functional genomics and increased interest in research. Faculty reported improved access to new technology and gains in understanding thanks to their involvement with GCAT. GCAT's network of supportive colleagues encourages faculty to explore genomics through student research and to learn a new and complex method with their undergraduates. GCAT is meeting important goals of BIO2010 by making research methods accessible to undergraduates, training faculty in genomics and bioinformatics, integrating mathematics into the biology curriculum, and increasing participation by underrepresented minority students.

ASSOCIATION BETWEEN VISUAL FUNCTION AND SUBRETINAL DRUSENOID DEPOSITS IN NORMAL AND EARLY AGE-RELATED MACULAR DEGENERATION EYES.

PubMed

Neely, David; Zarubina, Anna V; Clark, Mark E; Huisingh, Carrie E; Jackson, Gregory R; Zhang, Yuhua; McGwin, Gerald; Curcio, Christine A; Owsley, Cynthia

2017-07-01

To examine the association between subretinal drusenoid deposits (SDDs) identified by multimodal retinal imaging and visual function in older eyes with normal macular health or in the earliest phases of age-related macular degeneration (AMD). Age-related macular degeneration status for each eye was defined according to the Age-Related Eye Disease Study (AREDS) 9-step classification system (normal = Step 1, early AMD = Steps 2-4) based on color fundus photographs. Visual functions measured were best-corrected photopic visual acuity, contrast and light sensitivity, mesopic visual acuity, low-luminance deficit, and rod-mediated dark adaptation. Subretinal drusenoid deposits were identified through multimodal imaging (color fundus photographs, infrared reflectance and fundus autofluorescence images, and spectral domain optical coherence tomography). The sample included 1,202 eyes (958 eyes with normal health and 244 eyes with early AMD). In normal eyes, SDDs were not associated with any visual function evaluated. In eyes with early AMD, dark adaptation was markedly delayed in eyes with SDDs versus no SDD (a 4-minute delay on average), P = 0.0213. However, this association diminished after age adjustment, P = 0.2645. Other visual functions in early AMD eyes were not associated with SDDs. In a study specifically focused on eyes in normal macular health and in the earliest phases of AMD, early AMD eyes with SDDs have slower dark adaptation, largely attributable to the older ages of eyes with SDD; they did not exhibit deficits in other visual functions. Subretinal drusenoid deposits in older eyes in normal macular health are not associated with any visual functions evaluated.

Candidate genes for panhypopituitarism identified by gene expression profiling

PubMed Central

Mortensen, Amanda H.; MacDonald, James W.; Ghosh, Debashis

2011-01-01

Mutations in the transcription factors PROP1 and PIT1 (POU1F1) lead to pituitary hormone deficiency and hypopituitarism in mice and humans. The dysmorphology of developing Prop1 mutant pituitaries readily distinguishes them from those of Pit1 mutants and normal mice. This and other features suggest that Prop1 controls the expression of genes besides Pit1 that are important for pituitary cell migration, survival, and differentiation. To identify genes involved in these processes we used microarray analysis of gene expression to compare pituitary RNA from newborn Prop1 and Pit1 mutants and wild-type littermates. Significant differences in gene expression were noted between each mutant and their normal littermates, as well as between Prop1 and Pit1 mutants. Otx2, a gene critical for normal eye and pituitary development in humans and mice, exhibited elevated expression specifically in Prop1 mutant pituitaries. We report the spatial and temporal regulation of Otx2 in normal mice and Prop1 mutants, and the results suggest Otx2 could influence pituitary development by affecting signaling from the ventral diencephalon and regulation of gene expression in Rathke's pouch. The discovery that Otx2 expression is affected by Prop1 deficiency provides support for our hypothesis that identifying molecular differences in mutants will contribute to understanding the molecular mechanisms that control pituitary organogenesis and lead to human pituitary disease. PMID:21828248

Detecting early functional damage in glaucoma suspect and ocular hypertensive patients with the multifocal VEP technique.

PubMed

Thienprasiddhi, Phamornsak; Greenstein, Vivienne C; Chu, David H; Xu, Li; Liebmann, Jeffrey M; Ritch, Robert; Hood, Donald C

2006-08-01

To determine whether the multifocal visual evoked potential (mfVEP) technique can detect early functional damage in ocular hypertensive (OHT) and glaucoma suspect (GS) patients with normal standard achromatic automated perimetry (SAP) results. Twenty-five GS patients (25 eyes), 25 patients with OHT (25 eyes), and 50 normal controls (50 eyes) were enrolled in this study. All GS, OHT and normal control eyes had normal SAP as defined by a pattern standard deviation and mean deviation within the 95% confidence interval and a glaucoma hemifield test within normal limits on the Humphrey visual field 24-2 program. Eyes with GS had optic disc changes consistent with glaucoma with or without raised intraocular pressure (IOP), and eyes with OHT showed no evidence of glaucomatous optic neuropathy and IOPs >or=22 mm Hg. Monocular mfVEPs were obtained from both eyes of each subject using a pattern-reversal dartboard array with 60 sectors. The entire display had a radius of 22.3 degrees. The mfVEPs, for each eye, were defined as abnormal when either the monocular or interocular probability plot had a cluster of 3 or more contiguous points with P<0.05 and at least 2 of these points with P<0.01. The mfVEP results were abnormal in 4% of the eyes from normal subjects. Abnormal mfVEPs were detected in 20% of the eyes of GS patients and 16% of the eyes of OHT patients. Significantly more mfVEP abnormalities were detected in GS patients than in normal controls. However, there was no significant difference in mfVEP results between OHT patients and normal controls. The mfVEP technique can detect visual field deficits in a minority of eyes with glaucomatous optic disks and normal SAP results.

Upregulated epidermal growth factor receptor expression following near-infrared irradiation simulating solar radiation in a three-dimensional reconstructed human corneal epithelial tissue culture model.

PubMed

Tanaka, Yohei; Nakayama, Jun

2016-01-01

Humans are increasingly exposed to near-infrared (NIR) radiation from both natural (eg, solar) and artificial (eg, electrical appliances) sources. Although the biological effects of sun and ultraviolet (UV) exposure have been extensively investigated, the biological effect of NIR radiation is still unclear. We previously reported that NIR as well as UV induces photoaging and standard UV-blocking materials, such as sunglasses, do not sufficiently block NIR. The objective of this study was to investigate changes in gene expression in three-dimensional reconstructed corneal epithelial tissue culture exposed to broad-spectrum NIR irradiation to simulate solar NIR radiation that reaches human tissues. DNA microarray and quantitative real-time polymerase chain reaction analysis were used to assess gene expression levels in a three-dimensional reconstructed corneal epithelial model composed of normal human corneal epithelial cells exposed to water-filtered broad-spectrum NIR irradiation with a contact cooling (20°C). The water-filter allowed 1,000-1,800 nm wavelengths and excluded 1,400-1,500 nm wavelengths. A DNA microarray with >62,000 different probes showed 25 and 150 genes that were up- or downregulated by at least fourfold and twofold, respectively, after NIR irradiation. In particular, epidermal growth factor receptor (EGFR) was upregulated by 19.4-fold relative to control cells. Quantitative real-time polymerase chain reaction analysis revealed that two variants of EGFR in human corneal epithelial tissue were also significantly upregulated after five rounds of 10 J/cm(2) irradiation (P<0.05). We found that NIR irradiation induced the upregulated expression of EGFR in human corneal cells. Since over half of the solar energy reaching the Earth is in the NIR region, which cannot be adequately blocked by eyewear and thus can induce eye damage with intensive or long-term exposure, protection from both UV and NIR radiation may prevent changes in gene expression and in turn eye damage.

Removing technical variability in RNA-seq data using conditional quantile normalization.

PubMed

Hansen, Kasper D; Irizarry, Rafael A; Wu, Zhijin

2012-04-01

The ability to measure gene expression on a genome-wide scale is one of the most promising accomplishments in molecular biology. Microarrays, the technology that first permitted this, were riddled with problems due to unwanted sources of variability. Many of these problems are now mitigated, after a decade's worth of statistical methodology development. The recently developed RNA sequencing (RNA-seq) technology has generated much excitement in part due to claims of reduced variability in comparison to microarrays. However, we show that RNA-seq data demonstrate unwanted and obscuring variability similar to what was first observed in microarrays. In particular, we find guanine-cytosine content (GC-content) has a strong sample-specific effect on gene expression measurements that, if left uncorrected, leads to false positives in downstream results. We also report on commonly observed data distortions that demonstrate the need for data normalization. Here, we describe a statistical methodology that improves precision by 42% without loss of accuracy. Our resulting conditional quantile normalization algorithm combines robust generalized regression to remove systematic bias introduced by deterministic features such as GC-content and quantile normalization to correct for global distortions.

Genome Consortium for Active Teaching: Meeting the Goals of BIO2010

ERIC Educational Resources Information Center

Campbell, A. Malcolm; Ledbetter, Mary Lee S.; Hoopes, Laura L. M.; Eckdahl, Todd T.; Heyer, Laurie J.; Rosenwald, Anne; Fowlks, Edison; Tonidandel, Scott; Bucholtz, Brooke; Gottfried, Gail

2007-01-01

The Genome Consortium for Active Teaching (GCAT) facilitates the use of modern genomics methods in undergraduate education. Initially focused on microarray technology, but with an eye toward diversification, GCAT is a community working to improve the education of tomorrow's life science professionals. GCAT participants have access to affordable…

Optical coherence tomography measurement of the retinal nerve fiber layer in normal and juvenile glaucomatous eyes.

PubMed

Mrugacz, Malgorzata; Bakunowicz-Lazarczyk, Alina

2005-01-01

The aim of this study was to quantitatively assess and compare the thickness of the retinal nerve fiber layer (RNFL) in normal and glaucomatous eyes of children using the optical coherence tomograph. The mean RNFL thickness of normal eyes (n=26) was compared with that of glaucomatous eyes (n=26). The eyes were classified into diagnostic groups based on conventional ophthalmological physical examination, Humphrey 30-2 visual fields, stereoscopic optic nerve head photography, and optical coherence tomography. The mean RNFL was significantly thinner in glaucomatous eyes than in normal eyes: 95+/-26.3 and 132+/-24.5 microm, respectively. More specifically, the RNFL was significantly thinner in glaucomatous eyes than in normal eyes in the inferior quadrant: 87+/-23.5 and 122+/-24.2 microm, respectively. The mean and inferior quadrant RFNL thicknesses as measured by the optical coherence tomograph showed a statistically significant correlation with glaucoma. Optical coherence tomography may contribute to tracking of juvenile glaucoma progression. Copyright (c) 2005 S. Karger AG, Basel.

Eye-Specific Gene Expression following Embryonic Ethanol Exposure in Zebrafish: Roles for Heat Shock Factor 1

PubMed Central

Kashyap, Bhavani; Pegorsch, Laurel; Frey, Ruth A.; Sun, Chi; Shelden, Eric A.; Stenkamp, Deborah L.

2014-01-01

The mechanisms through which ethanol exposure results in developmental defects remain unclear. We used the zebrafish model to elucidate eye-specific mechanisms that underlie ethanol-mediated microphthalmia (reduced eye size), through time-series microarray analysis of gene expression within eyes of embryos exposed to 1.5% ethanol. 62 genes were differentially expressed (DE) in ethanol-treated as compared to control eyes sampled during retinal neurogenesis (24-48 hours post-fertilization). The EDGE (extraction of differential gene expression) algorithm identified >3000 genes DE over developmental time in ethanol-exposed eyes as compared to controls. The DE lists included several genes indicating a mis-regulated cellular stress response due to ethanol exposure. Combined treatment with sub-threshold levels of ethanol and a morpholino targeting heat shock factor 1 mRNA resulted in microphthalmia, suggesting convergent molecular pathways. Thermal preconditioning partially prevented ethanol-mediated microphthalmia while maintaining Hsf-1 expression. These data suggest roles for reduced Hsf-1 in mediating microphthalmic effects of embryonic ethanol exposure. PMID:24355176

Comparison of axial length, anterior chamber depth and intraocular lens power between IOLMaster and ultrasound in normal, long and short eyes.

PubMed

Dong, Jing; Zhang, Yaqin; Zhang, Haining; Jia, Zhijie; Zhang, Suhua; Wang, Xiaogang

2018-01-01

To compare the axial length (AL), anterior chamber depth (ACD) and intraocular lens power (IOLP) of IOLMaster and Ultrasound in normal, long and short eyes. Seventy-four normal eyes (≥ 22 mm and ≤ 25 mm), 74 long eyes (> 25 mm) and 78 short eyes (< 22 mm) underwent AL and ACD measurements with both devices in the order of IOLMaster followed by Ultrasound. The IOLP were calculated using a free online LADAS IOL formula calculator. The difference in AL and IOLP between IOLMaster and Ultrasound was statistically significant when all three groups were combined. The difference in ACD between IOLMaster and Ultrasound was statistically significant in the normal group (P<0.001) and short eye group (P<0.001) but not the long eye group (P = 0.465). For the IOLP difference between IOLMaster and Ultrasound in the normal group, the percentage of IOLP differences <|0.5|D, ≥|0.5|D<|0.75|D, ≥|0.75|D<|1.0|D, and ≥|1.0|D were 90.5%, 8.1%, 1.4% and 0%, respectively. For the long eye group, they were 90.5%, 5.4%, 4.1% and 0%, respectively. For the short eye group, they were 61.5%, 23.1%, 10.3%, and 5.1%, respectively. IOLMaster and Ultrasound have statistically significant differences in AL measurements and IOLP (using LADAS formula) for normal, long eye and short eye. The two instruments agree regarding ACD measurements for the long eye group, but differ for the normal and short eye groups. Moreover, the high percentage of IOLP differences greater than |0.5|D in the short eye group is noteworthy.

Adaptations and deficits in the vestibulo-ocular reflex after sixth nerve palsy.

PubMed

Wong, Agnes M F; Tweed, Douglas; Sharpe, James A

2002-01-01

The effects of paralytic strabismus on the vestibulo-ocular reflex (VOR) have not been systematically investigated in humans. The purpose of this study was to analyze the VOR in patients with unilateral peripheral sixth nerve palsy. Twenty-one patients with unilateral peripheral sixth nerve palsy (6 severe, 7 moderate, 8 mild) and 15 normal subjects were studied. Subjects made sinusoidal +/-10 degrees head-on-body rotations in yaw and pitch at approximately 0.5 and 2 Hz, and in roll at approximately 0.5, 1, and 2 Hz. Eye movement recordings were obtained using magnetic scleral search coils in each eye in darkness and during monocular viewing in light. Static torsional VOR gains, defined as change in torsional eye position divided by change in head position during sustained head roll, were also measured. In all patients, horizontal VOR gains in darkness were decreased in the paretic eye in both abduction and adduction, but remained normal in the nonparetic eye in both directions. In light, horizontal visually enhanced VOR (VVOR) gains were normal in both eyes in moderate and mild palsy. In severe palsy, horizontal VVOR gains remained low in the paretic eye during viewing with either eye, whereas those in the nonparetic eye were higher than normal when the paretic eye viewed. Vertical VOR and VVOR were normal, but dynamic and static torsional VOR and VVOR gains were reduced in both eyes in all patients. In darkness, horizontal VOR gains were reduced during abduction of the paretic eye in all patients, as anticipated in sixth nerve palsy. Gains were also reduced during adduction of the paretic eye, suggesting that innervation to the medial rectus has changed. After severe palsy, vision did not increase abducting or adducting horizontal VVOR gains to normal in the paretic eye, but caused secondary increase in VVOR gains to values above unity in the nonparetic eye, when the paretic eye fixated. In mild and moderate palsy, vision enhanced the VOR in the paretic eye but caused no change in the nonparetic eye, suggesting a monocular readjustment of innervation selectively to the paretic eye. Vertical VOR and VVOR gains were normal, indicating that the lateral rectus did not have significant vertical actions through the excursions that we tested (+/-10 degrees ). Reduced torsional VOR gains in the paretic eye can be explained by the esotropia in sixth nerve palsy. Torsional VOR gain normally varies with vergence. We attribute the reduced torsional gains in the paretic eye to the mechanism that normally lowers it during convergence. The low torsional gains in the nonparetic eye may be an adaptation to reduce torsional disparity between the two eyes.

Intra-Platform Repeatability and Inter-Platform Comparability of MicroRNA Microarray Technology

PubMed Central

Sato, Fumiaki; Tsuchiya, Soken; Terasawa, Kazuya; Tsujimoto, Gozoh

2009-01-01

Over the last decade, DNA microarray technology has provided a great contribution to the life sciences. The MicroArray Quality Control (MAQC) project demonstrated the way to analyze the expression microarray. Recently, microarray technology has been utilized to analyze a comprehensive microRNA expression profiling. Currently, several platforms of microRNA microarray chips are commercially available. Thus, we compared repeatability and comparability of five different microRNA microarray platforms (Agilent, Ambion, Exiqon, Invitrogen and Toray) using 309 microRNAs probes, and the Taqman microRNA system using 142 microRNA probes. This study demonstrated that microRNA microarray has high intra-platform repeatability and comparability to quantitative RT-PCR of microRNA. Among the five platforms, Agilent and Toray array showed relatively better performances than the others. However, the current lineup of commercially available microRNA microarray systems fails to show good inter-platform concordance, probably because of lack of an adequate normalization method and severe divergence in stringency of detection call criteria between different platforms. This study provided the basic information about the performance and the problems specific to the current microRNA microarray systems. PMID:19436744

Ectopic Six3 expression in the dragon eye goldfish.

PubMed

Ma, Dong-Mei; Zhu, Hua-Ping; Gui, Jian-Fang

2008-02-01

For goldfish (Carassius auratus), there are many varieties with different eye phenotypes due to artificial selection and adaptive evolution. Dragon eye is a variant eye characterized by a large-size eyeball protruding out of the socket similar to the eye of dragon in Chinese legends. In this study, anatomical structure of the goldfish dragon eye was compared with that of the common eye, and a stretching of the retina was observed in the enlarged dragon eye. Moreover, the homeobox-containing transcription factor Six3 cDNAs were cloned from the two types of goldfish, and the expression patterns were analyzed in both normal eye and dragon eye goldfish. No amino acid sequence differences were observed between the two deduced peptides, and the expression pattern of Six3 protein in dragon eye is quite similar to common eye during embryogenesis, but from 2 days after hatching, ectopic Six3 expression began to occur in the dragon eye, especially in the outer nuclear layer cells. With eye development, more predominant Six3 distribution was detected in the outer nuclear layer cells of dragon eye than that of normal eye, and fewer cell-layers in outer nuclear layer were observed in dragon eye retina than in normal eye retina. The highlight of this study is that higher Six3 expression occurs in dragon eye goldfish than in normal eye goldfish during retinal development of larvae.

Topography and Higher Order Corneal Aberrations of the Fellow Eye in Unilateral Keratoconus.

PubMed

Aksoy, Sibel; Akkaya, Sezen; Özkurt, Yelda; Kurna, Sevda; Açıkalın, Banu; Şengör, Tomris

2017-10-01

Comparison of topography and corneal higher order aberrations (HOA) data of fellow normal eyes of unilateral keratoconus patients with keratoconus eyes and control group. The records of 196 patients with keratoconus were reviewed. Twenty patients were identified as unilateral keratoconus. The best corrected visual acuity (BCVA), topography and aberration data of the unilateral keratoconus patients' normal eyes were compared with their contralateral keratoconus eyes and with control group eyes. For statistical analysis, flat and steep keratometry values, average corneal power, cylindrical power, surface regularity index (SRI), surface asymmetry index (SAI), inferior-superior ratio (I-S), keratoconus prediction index, and elevation-depression power (EDP) and diameter (EDD) topography indices were selected. Mean age of the unilateral keratoconus patients was 26.05±4.73 years and that of the control group was 23.6±8.53 years (p>0.05). There was no statistical difference in BCVA between normal and control eyes (p=0.108), whereas BCVA values were significantly lower in eyes with keratoconus (p=0.001). Comparison of quantitative topographic indices between the groups showed that all indices except the I-S ratio were significantly higher in the normal group than in the control group (p<0.05). The most obvious differences were in the SRI, SAI, EDP, and EDD values. All topographic indices were higher in the keratoconus eyes compared to the normal fellow eyes. There was no difference between normal eyes and the control group in terms of spherical aberration, while coma, trefoil, irregular astigmatism, and total HOA values were higher in the normal eyes of unilateral keratoconus patients (p<0.05). All HOA values were higher in keratoconus eyes than in the control group. According to our study, SRI, SAI, EDP, EDD values, and HOA other than spherical aberration were higher in the clinically and topographically normal fellow eyes of unilateral keratoconus patients when compared to a control group. This finding may be due to the mild asymmetric and morphologic changes in the subclinical stage of keratoconus leading to deterioration in the indicators of corneal irregularity and elevation changes. Therefore, these eyes may be exhibiting the early form of the disease.

Aberrant expression of long noncoding RNAs in cumulus cells isolated from PCOS patients.

PubMed

Huang, Xin; Hao, Cuifang; Bao, Hongchu; Wang, Meimei; Dai, Huangguan

2016-01-01

To describe the long noncoding RNA (lncRNA) profiles in cumulus cells isolated from polycystic ovary syndrome (PCOS) patients by employing a microarray and in-depth bioinformatics analysis. This information will help us understand the occurrence and development of PCOS. In this study, we used a microarray to describe lncRNA profiles in cumulus cells isolated from ten patients (five PCOS and five normal women). Several differentially expressed lncRNAs were chosen to validate the microarray results by quantitative RT-PCR (qRT-PCR). Then, the differentially expressed lncRNAs were classified into three subgroups (HOX loci lncRNA, enhancer-like lncRNA, and lincRNA) to deduce their potential features. Furthermore, a lncRNA/mRNA co-expression network was constructed by using the Cytoscape software (V2.8.3, http://www.cytoscape.org/ ). We observed that 623 lncRNAs and 260 messenger RNAs (mRNAs) were significantly up- or down-regulated (≥2-fold change), and these differences could be used to discriminate cumulus cells of PCOS from those of normal patients. Five differentially expressed lncRNAs (XLOC_011402, ENST00000454271, ENST00000433673, ENST00000450294, and ENST00000432431) were selected to validate the microarray results using quantitative RT-PCR (qRT-PCR). The qRT-PCR results were consistent with the microarray data. Further analysis indicated that many differentially expressed lncRNAs were transcribed from chromosome 2 and may act as enhancers to regulate their neighboring protein-coding genes. Forty-three lncRNAs and 29 mRNAs were used to construct the coding-non-coding gene co-expression network. Most pairs positively correlated, and one mRNA correlated with one or more lncRNAs. Our study is the first to determine genome-wide lncRNA expression patterns in cumulus cells isolated from PCOS patients by microarray. The results show that clusters of lncRNAs were aberrantly expressed in cumulus cells of PCOS patients compared with those of normal women, which revealed that lncRNAs differentially expressed in PCOS and normal women may contribute to the occurrence of PCOS and affect oocyte development.

Peripapillary Pachychoroid in Nonarteritic Anterior Ischemic Optic Neuropathy

PubMed Central

Nagia, Lina; Huisingh, Carrie; Johnstone, John; Kline, Lanning B.; Clark, Mark; Girard, Michael J. A.; Mari, Jean Martial; Girkin, Christopher A.

2016-01-01

Purpose This study examined the peripapillary choroidal thickness (PCT) in nonarteritic ischemic optic neuropathy (NAION) in comparison to contralateral eyes and normal eyes. Methods We used enhanced depth imaging spectral-domain optical coherence tomography to image the optic nerve head of 20 NAION, 10 contralateral eyes, and 102 normal eyes. Following compensation, the scans were manually delineated to identify relevant surfaces including Bruch's membrane opening (BMO), Bruch's membrane, and anterior sclera. The PCT was defined as the measurement between Bruch's membrane and the anterior sclera and was measured at increasing distance from BMO. Models adjusted for age, BMO area, and axial length were used to compare the mean PCT between NAION and normal eyes, and contralateral eyes and normal eyes. Paired t-tests were used to compare the PCT between NAION and contralateral eyes. Results The mean PCT was thicker in NAION and contralateral eyes when compared with normal eyes at all distances from BMO (P < 0.001). The PCT was not significantly thicker in contralateral eyes when compared with affected NAION eyes. Choroidal thickness was thinnest in the inferior quadrant in all eyes regardless of the group. Conclusions Increased peripapillary choroidal thickness was noted in both NAION and contralateral eyes. The thicker choroid may be an associated feature or a result of the disorder. Although further longitudinal study is required to determine causation, these findings may suggest that a thickened peripapillary choroid may be a component of the disk-at-risk clinical phenotype. PMID:27583829

Development of infrared thermal imager for dry eye diagnosis

NASA Astrophysics Data System (ADS)

Chiang, Huihua Kenny; Chen, Chih Yen; Cheng, Hung You; Chen, Ko-Hua; Chang, David O.

2006-08-01

This study aims at the development of non-contact dry eye diagnosis based on an infrared thermal imager system, which was used to measure the cooling of the ocular surface temperature of normal and dry eye patients. A total of 108 subjects were measured, including 26 normal and 82 dry eye patients. We have observed that the dry eye patients have a fast cooling of the ocular surface temperature than the normal control group. We have developed a simplified algorithm for calculating the temperature decay constant of the ocular surface for discriminating between normal and dry eye. This study shows the diagnostic of dry eye syndrome by the infrared thermal imager system has reached a sensitivity of 79.3%, a specificity of 75%, and the area under the ROC curve 0.841. The infrared thermal imager system has a great potential to be developed for dry eye screening with the advantages of non-contact, fast, and convenient implementation.

Biomarkers of the Hedgehog/Smoothened pathway in healthy volunteers

PubMed Central

Kadam, Sunil K; Patel, Bharvin K R; Jones, Emma; Nguyen, Tuan S; Verma, Lalit K; Landschulz, Katherine T; Stepaniants, Sergey; Li, Bin; Brandt, John T; Brail, Leslie H

2012-01-01

The Hedgehog (Hh) pathway is involved in oncogenic transformation and tumor maintenance. The primary objective of this study was to select surrogate tissue to measure messenger ribonucleic acid (mRNA) levels of Hh pathway genes for measurement of pharmacodynamic effect. Expression of Hh pathway specific genes was measured by quantitative real time polymerase chain reaction (qRT-PCR) and global gene expression using Affymetrix U133 microarrays. Correlations were made between the expression of specific genes determined by qRT-PCR and normalized microarray data. Gene ontology analysis using microarray data for a broader set of Hh pathway genes was performed to identify additional Hh pathway-related markers in the surrogate tissue. RNA extracted from blood, hair follicle, and skin obtained from healthy subjects was analyzed by qRT-PCR for 31 genes, whereas 8 samples were analyzed for a 7-gene subset. Twelve sample sets, each with ≤500 ng total RNA derived from hair, skin, and blood, were analyzed using Affymetrix U133 microarrays. Transcripts for several Hh pathway genes were undetectable in blood using qRT-PCR. Skin was the most desirable matrix, followed by hair follicle. Whether processed by robust multiarray average or microarray suite 5 (MAS5), expression patterns of individual samples showed co-clustered signals; both normalization methods were equally effective for unsupervised analysis. The MAS5- normalized probe sets appeared better suited for supervised analysis. This work provides the basis for selection of a surrogate tissue and an expression analysis-based approach to evaluate pathway-related genes as markers of pharmacodynamic effect with novel inhibitors of the Hh pathway. PMID:22611475

Effects of 0.2% brimonidine and 0.2% brimonidine-0.5% timolol on intraocular pressure and pupil size in normal equine eyes.

PubMed

Von Zup, M; Lassaline, M; Kass, P H; Miller, P E; Thomasy, S M

2017-11-01

Brimonidine is an α 2 -adrenergic agonist that decreases aqueous humour production and may increase uveoscleral outflow. It has not been evaluated in normal or glaucomatous equine eyes. To evaluate the efficacy and safety of brimonidine in lowering intraocular pressure (IOP), alone and in conjunction with timolol, as a treatment for equine glaucoma by comparing IOP in normal equine eyes treated with brimonidine and brimonidine-timolol, respectively, with IOP in control eyes. A balanced crossover design with 16 horses receiving one of two treatments, brimonidine and brimonidine-timolol, during each of two 10-day study phases, was used. Four horses were randomly assigned to each of four combinations of treated eye (right or left) and drug order within the two 10-day study phases (brimonidine first or brimonidine-timolol first). Pupil size and conjunctival hyperaemia were assessed twice per day and IOP was measured three times per day using rebound tonometry in both eyes of 16 normal horses throughout two 10-day study periods (brimonidine and brimonidine-timolol) separated by an 18-day washout period. One eye of each horse was treated with brimonidine or brimonidine-timolol and the opposite eye was treated with balanced salt solution (BSS). There were no adverse effects and no significant changes in pupil size in normal equine eyes treated with brimonidine or brimonidine-timolol. Average IOP in normal equine eyes treated with brimonidine (25.6 mmHg) was statistically higher than in eyes treated with brimonidine-timolol (24.6 mmHg) or BSS (24.5 mmHg). However, IOP differences were of ≤1 mmHg and thus not clinically important. Horses with normal eyes may not be as sensitive to the IOP-lowering effects of treatment as horses with glaucoma. Brimonidine and brimonidine-timolol are well tolerated in normal horses but do not decrease IOP. © 2017 EVJ Ltd.

Evaluation of Different Normalization and Analysis Procedures for Illumina Gene Expression Microarray Data Involving Small Changes

PubMed Central

Johnstone, Daniel M.; Riveros, Carlos; Heidari, Moones; Graham, Ross M.; Trinder, Debbie; Berretta, Regina; Olynyk, John K.; Scott, Rodney J.; Moscato, Pablo; Milward, Elizabeth A.

2013-01-01

While Illumina microarrays can be used successfully for detecting small gene expression changes due to their high degree of technical replicability, there is little information on how different normalization and differential expression analysis strategies affect outcomes. To evaluate this, we assessed concordance across gene lists generated by applying different combinations of normalization strategy and analytical approach to two Illumina datasets with modest expression changes. In addition to using traditional statistical approaches, we also tested an approach based on combinatorial optimization. We found that the choice of both normalization strategy and analytical approach considerably affected outcomes, in some cases leading to substantial differences in gene lists and subsequent pathway analysis results. Our findings suggest that important biological phenomena may be overlooked when there is a routine practice of using only one approach to investigate all microarray datasets. Analytical artefacts of this kind are likely to be especially relevant for datasets involving small fold changes, where inherent technical variation—if not adequately minimized by effective normalization—may overshadow true biological variation. This report provides some basic guidelines for optimizing outcomes when working with Illumina datasets involving small expression changes. PMID:27605185

Identification and Comparison of the Polar Phospholipids in Normal and Dry Eye Rabbit Tears by MALDI-TOF Mass Spectrometry

PubMed Central

Ham, Bryan M.; Cole, Richard B.; Jacob, Jean T.

2008-01-01

Purpose To identify and compare the phosphorylated lipids in normal and dry eye rabbit tears using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Methods MALDI-TOF MS studies were performed on tear samples from normal and dry eyes of female New Zealand White rabbits. Experimental dry eye was induced by complete removal of the main and accessory lacrimal glands and nictitating membranes. A solid ionic crystal MALDI matrix of paranitroaniline and butyric acid was used to enhance the mass spectral responses of the phospholipids. In addition, a novel lipid isolation, preconcentration, and clean-up method using pipettes containing immobilized metal ion affinity chromatography (IMAC) medium was used. Results The polar phospholipids present in the normal and dry eye rabbit tears showed both similarities and differences. Species related to platelet-activating factor (PAF) and/or lysophosphatidylcholine (lyso-PC), phosphatidylcholine (PC), and sphingomyelin (SM) were found in both the normal and dry eye rabbit tears. However, the number of types and the concentrations of SM molecules were markedly greater in the dry eye tears than in the normal tears. In addition, phosphatidylserine (PS) species that were readily detectable in dry eye tears were not found in normal tears. Conclusions The combination of immobilized metal ion affinity chromatography and the solid ionic crystal matrix for MALDI enabled the detection and study of phosphorylated lipids in the tears. Specific differences between phospholipid levels in normal and dry eye tears were observable with this methodology. The appearance of various SM species only in the dry eye tears may provide markers for this disease state in the future. PMID:16877399

Monocular oral reading after treatment of dense congenital unilateral cataract

PubMed Central

Birch, Eileen E.; Cheng, Christina; Christina, V; Stager, David R.

2010-01-01

Background Good long-term visual acuity outcomes for children with dense congenital unilateral cataracts have been reported following early surgery and good compliance with postoperative amblyopia therapy. However, treated eyes rarely achieve normal visual acuity and there has been no formal evaluation of the utility of the treated eye for reading. Methods Eighteen children previously treated for dense congenital unilateral cataract were tested monocularly with the Gray Oral Reading Test, 4th edition (GORT-4) at 7 to 13 years of age using two passages for each eye, one at grade level and one at +1 above grade level. In addition, right eyes of 55 normal children age 7 to 13 served as a control group. The GORT-4 assesses reading rate, accuracy, fluency, and comprehension. Results Visual acuity of treated eyes ranged from 0.1 to 2.0 logMAR and of fellow eyes from −0.1 to 0.2 logMAR. Treated eyes scored significantly lower than fellow and normal control eyes on all scales at grade level and at +1 above grade level. Monocular reading rate, accuracy, fluency, and comprehension were correlated with visual acuity of treated eyes (rs = −0.575 to −0.875, p < 0.005). Treated eyes with 0.1-0.3 logMAR visual acuity did not differ from fellow or normal control eyes in rate, accuracy, fluency, or comprehension when reading at grade level or at +1 above grade level. Fellow eyes did not differ from normal controls on any reading scale. Conclusions Excellent visual acuity outcomes following treatment of dense congenital unilateral cataracts are associated with normal reading ability of the treated eye in school-age children. PMID:20603057

Identifying molecular features for prostate cancer with Gleason 7 based on microarray gene expression profiles.

PubMed

Bălăcescu, Loredana; Bălăcescu, O; Crişan, N; Fetica, B; Petruţ, B; Bungărdean, Cătălina; Rus, Meda; Tudoran, Oana; Meurice, G; Irimie, Al; Dragoş, N; Berindan-Neagoe, Ioana

2011-01-01

Prostate cancer represents the first leading cause of cancer among western male population, with different clinical behavior ranging from indolent to metastatic disease. Although many molecules and deregulated pathways are known, the molecular mechanisms involved in the development of prostate cancer are not fully understood. The aim of this study was to explore the molecular variation underlying the prostate cancer, based on microarray analysis and bioinformatics approaches. Normal and prostate cancer tissues were collected by macrodissection from prostatectomy pieces. All prostate cancer specimens used in our study were Gleason score 7. Gene expression microarray (Agilent Technologies) was used for Whole Human Genome evaluation. The bioinformatics and functional analysis were based on Limma and Ingenuity software. The microarray analysis identified 1119 differentially expressed genes between prostate cancer and normal prostate, which were up- or down-regulated at least 2-fold. P-values were adjusted for multiple testing using Benjamini-Hochberg method with a false discovery rate of 0.01. These genes were analyzed with Ingenuity Pathway Analysis software and were established 23 genetic networks. Our microarray results provide new information regarding the molecular networks in prostate cancer stratified as Gleason 7. These data highlighted gene expression profiles for better understanding of prostate cancer progression.

AccuTyping: new algorithms for automated analysis of data from high-throughput genotyping with oligonucleotide microarrays

PubMed Central

Hu, Guohong; Wang, Hui-Yun; Greenawalt, Danielle M.; Azaro, Marco A.; Luo, Minjie; Tereshchenko, Irina V.; Cui, Xiangfeng; Yang, Qifeng; Gao, Richeng; Shen, Li; Li, Honghua

2006-01-01

Microarray-based analysis of single nucleotide polymorphisms (SNPs) has many applications in large-scale genetic studies. To minimize the influence of experimental variation, microarray data usually need to be processed in different aspects including background subtraction, normalization and low-signal filtering before genotype determination. Although many algorithms are sophisticated for these purposes, biases are still present. In the present paper, new algorithms for SNP microarray data analysis and the software, AccuTyping, developed based on these algorithms are described. The algorithms take advantage of a large number of SNPs included in each assay, and the fact that the top and bottom 20% of SNPs can be safely treated as homozygous after sorting based on their ratios between the signal intensities. These SNPs are then used as controls for color channel normalization and background subtraction. Genotype calls are made based on the logarithms of signal intensity ratios using two cutoff values, which were determined after training the program with a dataset of ∼160 000 genotypes and validated by non-microarray methods. AccuTyping was used to determine >300 000 genotypes of DNA and sperm samples. The accuracy was shown to be >99%. AccuTyping can be downloaded from . PMID:16982644

Microarray-based identification of differentially expressed genes in extramammary Paget’s disease

PubMed Central

Lin, Jin-Ran; Liang, Jun; Zhang, Qiao-An; Huang, Qiong; Wang, Shang-Shang; Qin, Hai-Hong; Chen, Lian-Jun; Xu, Jin-Hua

2015-01-01

Extramammary Paget’s disease (EMPD) is a rare cutaneous malignancy accounting for approximately 1-2% of vulvar cancers. The rarity of this disease has caused difficulties in characterization and the molecular mechanism underlying EMPD development remains largely unclear. Here we used microarray analysis to identify differentially expressed genes in EMPD of the scrotum comparing with normal epithelium from healthy donors. Agilent single-channel microarray was used to compare the gene expression between 6 EMPD specimens and 6 normal scrotum epithelium samples. A total of 799 up-regulated genes and 723 down-regulated genes were identified in EMPD tissues. Real-time PCR was conducted to verify the differential expression of some representative genes, including ERBB4, TCF3, PAPSS2, PIK3R3, PRLR, SULT1A1, TCF7L1, and CREB3L4. Generally, the real-time PCR results were consistent with microarray data, and the expression of ERBB4, PRLR, TCF3, PIK3R3, SULT1A1, and TCF7L1 was significantly overexpressed in EMPD (P<0.05). Moreover, the overexpression of PRLR in EMPD, a receptor for the anterior pituitary hormone prolactin (PRL), was confirmed by immunohistochemistry. These data demonstrate that the differentially expressed genes from the microarray-based identification are tightly associated with EMPD occurrence. PMID:26221264

A Unique Procedure to Identify Cell Surface Markers Through a Spherical Self-Organizing Map Applied to DNA Microarray Analysis.

PubMed

Sugii, Yuh; Kasai, Tomonari; Ikeda, Masashi; Vaidyanath, Arun; Kumon, Kazuki; Mizutani, Akifumi; Seno, Akimasa; Tokutaka, Heizo; Kudoh, Takayuki; Seno, Masaharu

2016-01-01

To identify cell-specific markers, we designed a DNA microarray platform with oligonucleotide probes for human membrane-anchored proteins. Human glioma cell lines were analyzed using microarray and compared with normal and fetal brain tissues. For the microarray analysis, we employed a spherical self-organizing map, which is a clustering method suitable for the conversion of multidimensional data into two-dimensional data and displays the relationship on a spherical surface. Based on the gene expression profile, the cell surface characteristics were successfully mirrored onto the spherical surface, thereby distinguishing normal brain tissue from the disease model based on the strength of gene expression. The clustered glioma-specific genes were further analyzed by polymerase chain reaction procedure and immunocytochemical staining of glioma cells. Our platform and the following procedure were successfully demonstrated to categorize the genes coding for cell surface proteins that are specific to glioma cells. Our assessment demonstrates that a spherical self-organizing map is a valuable tool for distinguishing cell surface markers and can be employed in marker discovery studies for the treatment of cancer.

Empirical evaluation of data normalization methods for molecular classification.

PubMed

Huang, Huei-Chung; Qin, Li-Xuan

2018-01-01

Data artifacts due to variations in experimental handling are ubiquitous in microarray studies, and they can lead to biased and irreproducible findings. A popular approach to correct for such artifacts is through post hoc data adjustment such as data normalization. Statistical methods for data normalization have been developed and evaluated primarily for the discovery of individual molecular biomarkers. Their performance has rarely been studied for the development of multi-marker molecular classifiers-an increasingly important application of microarrays in the era of personalized medicine. In this study, we set out to evaluate the performance of three commonly used methods for data normalization in the context of molecular classification, using extensive simulations based on re-sampling from a unique pair of microRNA microarray datasets for the same set of samples. The data and code for our simulations are freely available as R packages at GitHub. In the presence of confounding handling effects, all three normalization methods tended to improve the accuracy of the classifier when evaluated in an independent test data. The level of improvement and the relative performance among the normalization methods depended on the relative level of molecular signal, the distributional pattern of handling effects (e.g., location shift vs scale change), and the statistical method used for building the classifier. In addition, cross-validation was associated with biased estimation of classification accuracy in the over-optimistic direction for all three normalization methods. Normalization may improve the accuracy of molecular classification for data with confounding handling effects; however, it cannot circumvent the over-optimistic findings associated with cross-validation for assessing classification accuracy.

The use of open source bioinformatics tools to dissect transcriptomic data.

PubMed

Nitsche, Benjamin M; Ram, Arthur F J; Meyer, Vera

2012-01-01

Microarrays are a valuable technology to study fungal physiology on a transcriptomic level. Various microarray platforms are available comprising both single and two channel arrays. Despite different technologies, preprocessing of microarray data generally includes quality control, background correction, normalization, and summarization of probe level data. Subsequently, depending on the experimental design, diverse statistical analysis can be performed, including the identification of differentially expressed genes and the construction of gene coexpression networks.We describe how Bioconductor, a collection of open source and open development packages for the statistical programming language R, can be used for dissecting microarray data. We provide fundamental details that facilitate the process of getting started with R and Bioconductor. Using two publicly available microarray datasets from Aspergillus niger, we give detailed protocols on how to identify differentially expressed genes and how to construct gene coexpression networks.

Visual function assessment in simulated real-life situations in patients with age-related macular degeneration compared to normal subjects.

PubMed

Barteselli, G; Gomez, M L; Doede, A L; Chhablani, J; Gutstein, W; Bartsch, D-U; Dustin, L; Azen, S P; Freeman, W R

2014-10-01

To evaluate visual function variations in eyes with age-related macular degeneration (AMD) compared to normal eyes under different light/contrast conditions using a time-dependent visual acuity testing instrument, the Central Vision Analyzer (CVA). Overall, 37 AMD eyes and 35 normal eyes were consecutively tested with the CVA after assessing best-corrected visual acuity (BCVA) using ETDRS charts. The CVA established visual thresholds for three mesopic environments (M1 (high contrast), M2 (medium contrast), and M3 (low contrast)) and three backlight-glare environments (G1 (high contrast, equivalent to ETDRS), G2 (medium contrast), and G3 (low contrast)) under timed conditions. Vision drop across environments was calculated, and repeatability of visual scores was determined. BCVA significantly reduced with decreasing contrast in all eyes. M1 scores for BCVA were greater than M2 and M3 (P<0.001); G1 scores were greater than G2 and G3 (P<0.01). BCVA dropped more in AMD eyes than in normal eyes between M1 and M2 (P=0.002) and between M1 and M3 (P=0.003). In AMD eyes, BCVA was better using ETDRS charts compared to G1 (P<0.001). The drop in visual function between ETDRS and G1 was greater in AMD eyes compared to normal eyes (P=0.004). Standard deviations of test-retest ranged from 0.100 to 0.139 logMAR. The CVA allowed analysis of the visual complaints that AMD patients experience with different lighting/contrast time-dependent conditions. BCVA changed significantly under different lighting/contrast conditions in all eyes, however, AMD eyes were more affected by contrast reduction than normal eyes. In AMD eyes, timed conditions using the CVA led to worse BCVA compared to non-timed ETDRS charts.

Glaucoma Diagnostic Capabilities of Foveal Avascular Zone Parameters Using Optical Coherence Tomography Angiography According to Visual Field Defect Location.

PubMed

Kwon, Junki; Choi, Jaewan; Shin, Joong Won; Lee, Jiyun; Kook, Michael S

2017-12-01

To assess the diagnostic ability of foveal avascular zone (FAZ) parameters to discriminate glaucomatous eyes with visual field defects (VFDs) in different locations (central vs. peripheral) from normal eyes. Totally, 125 participants were separated into 3 groups: normal (n=45), glaucoma with peripheral VFD (PVFD, n=45), and glaucoma with central VFD (CVFD, n=35). The FAZ area, perimeter, and circularity and parafoveal vessel density were calculated from optical coherence tomography angiography images. The diagnostic ability of the FAZ parameters and other structural parameters was determined according to glaucomatous VFD location. Associations between the FAZ parameters and central visual function were evaluated. A larger FAZ area and longer FAZ perimeter were observed in the CVFD group than in the PVFD and normal groups. The FAZ area, perimeter, and circularity were better in differentiating glaucomatous eyes with CVFDs from normal eyes [areas under the receiver operating characteristic curves (AUC), 0.78 to 0.88] than in differentiating PVFDs from normal eyes (AUC, 0.51 to 0.64). The FAZ perimeter had a similar AUC value to the circumpapillary retinal nerve fiber layer and macular ganglion cell-inner plexiform layer thickness for differentiating eyes with CVFDs from normal eyes (all P>0.05, the DeLong test). The FAZ area was significantly correlated with central visual function (β=-112.7, P=0.035, multivariate linear regression). The FAZ perimeter had good diagnostic capability in differentiating glaucomatous eyes with CVFDs from normal eyes, and may be a potential diagnostic biomarker for detecting glaucomatous patients with CVFDs.

Extraocular muscle function testing

MedlinePlus

... may result in double vision or rapid, uncontrolled eye movements . Normal Results Normal movement of the eyes in all directions. What Abnormal Results Mean Eye movement disorders may be due to abnormalities of the ...

Quantitative analysis of iris parameters in keratoconus patients using optical coherence tomography.

PubMed

Bonfadini, Gustavo; Arora, Karun; Vianna, Lucas M; Campos, Mauro; Friedman, David; Muñoz, Beatriz; Jun, Albert S

2015-01-01

To investigate the relationship between quantitative iris parameters and the presence of keratoconus. Cross-sectional observational study that included 15 affected eyes of 15 patients with keratoconus and 26 eyes of 26 normal age- and sex-matched controls. Iris parameters (area, thickness, and pupil diameter) of affected and unaffected eyes were measured under standardized light and dark conditions using anterior segment optical coherence tomography (AS-OCT). To identify optimal iris thickness cutoff points to maximize the sensitivity and specificity when discriminating keratoconus eyes from normal eyes, the analysis included the use of receiver operating characteristic (ROC) curves. Iris thickness and area were lower in keratoconus eyes than in normal eyes. The mean thickness at the pupillary margin under both light and dark conditions was found to be the best parameter for discriminating normal patients from keratoconus patients. Diagnostic performance was assessed by the area under the ROC curve (AROC), which had a value of 0.8256 with 80.0% sensitivity and 84.6% specificity, using a cutoff of 0.4125 mm. The sensitivity increased to 86.7% when a cutoff of 0.4700 mm was used. In our sample, iris thickness was lower in keratoconus eyes than in normal eyes. These results suggest that tomographic parameters may provide novel adjunct approaches for keratoconus screening.

Diagnostic ability of macular ganglion cell-inner plexiform layer thickness in glaucoma suspects.

PubMed

Xu, Xiaoyu; Xiao, Hui; Guo, Xinxing; Chen, Xiangxi; Hao, Linlin; Luo, Jingyi; Liu, Xing

2017-12-01

The purpose is to assess the diagnostic ability for early glaucoma of macular ganglion cell-inner plexiform layer (GCIPL) thickness in a Chinese population including glaucoma suspects.A total of 367 eyes with primary open-angle glaucoma (168 early glaucoma, 78 moderate glaucoma, and 121 advanced glaucoma), 52 eyes with ocular hypertension (OHT), 59 eyes with enlarged cup-to-disc ratio (C/D), and 225 normal eyes were included. GCIPL thickness (average, minimum, superotemporal, superior, superonasal, inferonasal, inferior, and inferotemporal), retinal nerve fiber layer (RNFL) thickness, and optic nerve head (ONH) parameters were measured using Cirrus high-definition optical coherence tomography (OCT) and compared. The diagnostic ability of OCT parameters was assessed by area under receiver operating characteristic curve (AUROC) in 3 distinguishing groups: normal eyes and eyes with early glaucoma, normal eyes and eyes with glaucoma regardless of disease stage, and nonglaucomatous eyes (normal eyes, eyes with OHT, and enlarged C/D) and early glaucomatous eyes.Glaucomatous eyes showed a significant reduction in GCIPL thickness compared with nonglaucomatous eyes. In all 3 distinguishing groups, best-performing parameters of GCIPL thickness, RNFL thickness, and ONH parameters were minimum GCIPL thickness (expressed in AUROC, 0.899, 0.952, and 0.900, respectively), average RNFL thickness (0.904, 0.953, and 0.892, respectively), and rim area (0.861, 0.925, and 0.824, respectively). There was no statistical significance of AUROC between minimum GCIPL thickness and average RNFL thickness (all P > .05).GCIPL thickness could discriminate early glaucoma from normal and glaucoma suspects with good sensitivity and specificity. The glaucoma diagnostic ability of GCIPL thickness was comparable to that of RNFL thickness. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

Fully Automated Complementary DNA Microarray Segmentation using a Novel Fuzzy-based Algorithm.

PubMed

Saberkari, Hamidreza; Bahrami, Sheyda; Shamsi, Mousa; Amoshahy, Mohammad Javad; Ghavifekr, Habib Badri; Sedaaghi, Mohammad Hossein

2015-01-01

DNA microarray is a powerful approach to study simultaneously, the expression of 1000 of genes in a single experiment. The average value of the fluorescent intensity could be calculated in a microarray experiment. The calculated intensity values are very close in amount to the levels of expression of a particular gene. However, determining the appropriate position of every spot in microarray images is a main challenge, which leads to the accurate classification of normal and abnormal (cancer) cells. In this paper, first a preprocessing approach is performed to eliminate the noise and artifacts available in microarray cells using the nonlinear anisotropic diffusion filtering method. Then, the coordinate center of each spot is positioned utilizing the mathematical morphology operations. Finally, the position of each spot is exactly determined through applying a novel hybrid model based on the principle component analysis and the spatial fuzzy c-means clustering (SFCM) algorithm. Using a Gaussian kernel in SFCM algorithm will lead to improving the quality in complementary DNA microarray segmentation. The performance of the proposed algorithm has been evaluated on the real microarray images, which is available in Stanford Microarray Databases. Results illustrate that the accuracy of microarray cells segmentation in the proposed algorithm reaches to 100% and 98% for noiseless/noisy cells, respectively.

Multiplex cDNA quantification method that facilitates the standardization of gene expression data

PubMed Central

Gotoh, Osamu; Murakami, Yasufumi; Suyama, Akira

2011-01-01

Microarray-based gene expression measurement is one of the major methods for transcriptome analysis. However, current microarray data are substantially affected by microarray platforms and RNA references because of the microarray method can provide merely the relative amounts of gene expression levels. Therefore, valid comparisons of the microarray data require standardized platforms, internal and/or external controls and complicated normalizations. These requirements impose limitations on the extensive comparison of gene expression data. Here, we report an effective approach to removing the unfavorable limitations by measuring the absolute amounts of gene expression levels on common DNA microarrays. We have developed a multiplex cDNA quantification method called GEP-DEAN (Gene expression profiling by DCN-encoding-based analysis). The method was validated by using chemically synthesized DNA strands of known quantities and cDNA samples prepared from mouse liver, demonstrating that the absolute amounts of cDNA strands were successfully measured with a sensitivity of 18 zmol in a highly multiplexed manner in 7 h. PMID:21415008

Müllerian Agenesis in Cat Eye Syndrome and 22q11 Chromosome Abnormalities: A Case Report and Literature Review.

PubMed

AlSubaihin, Abdulmajeed; VanderMeulen, John; Harris, Kate; Duck, John; McCready, Elizabeth

2018-04-01

Although Müllerian agenesis is the second most common cause of primary amenorrhea the underlying etiology in most cases is unknown. Müllerian agenesis has been reported as a rare finding associated with chromosomal aberrations of the 22q11 chromosomal region including at least 1 individual with cat eye syndrome (CES) and 10 individuals with deletions or duplications of the 22q11.2 region. However, a potential link between 22q11 abnormalities and uterine malformations has been difficult to adequately ascertain because of the limited case reports in the literature. We report a second case of Müllerian agenesis in a girl with CES. A 16-year-old girl presented with bilateral colobomata, primary amenorrhea, and absence of the uterus and upper vagina on pelvic magnetic resonance imaging. Microarray analysis showed tetrasomy of the pericentromeric region of chromosome 22 diagnostic of CES. Müllerian aplasia/hypoplasia might represent a rare feature in CES and should be considered in the investigation of young girls with this syndrome. An increasing number of cases with 22q11 chromosome abnormalities and Müllerian agenesis further highlights the possibility of a gene within the 22q11 region that might mediate normal Müllerian development in girls. Copyright © 2017 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

The Role of the Immune Response in the Pathogenesis of Thyroid Eye Disease: A Reassessment

PubMed Central

Rosenbaum, James T.; Choi, Dongseok; Wong, Amanda; Wilson, David J.; Grossniklaus, Hans E.; Harrington, Christina A.; Dailey, Roger A.; Ng, John D.; Steele, Eric A.; Czyz, Craig N.; Foster, Jill A.; Tse, David; Alabiad, Chris; Dubovy, Sander; Parekh, Prashant K.; Harris, Gerald J.; Kazim, Michael; Patel, Payal J.; White, Valerie A.; Dolman, Peter J.; Edward, Deepak P.; Alkatan, Hind M.; al Hussain, Hailah; Selva, Dinesh; Yeatts, R. Patrick; Korn, Bobby S.; Kikkawa, Don O.; Stauffer, Patrick; Planck, Stephen R.

2015-01-01

Background Although thyroid eye disease is a common complication of Graves’ disease, the pathogenesis of the orbital disease is poorly understood. Most authorities implicate the immune response as an important causal factor. We sought to clarify pathogenesis by using gene expression microarray. Methods An international consortium of ocular pathologists and orbital surgeons contributed formalin fixed orbital biopsies. RNA was extracted from orbital tissue from 20 healthy controls, 25 patients with thyroid eye disease (TED), 25 patients with nonspecific orbital inflammation (NSOI), 7 patients with sarcoidosis and 6 patients with granulomatosis with polyangiitis (GPA). Tissue was divided into a discovery set and a validation set. Gene expression was quantified using Affymetrix U133 Plus 2.0 microarrays which include 54,000 probe sets. Results Principal component analysis showed that gene expression from tissue from patients with TED more closely resembled gene expression from healthy control tissue in comparison to gene expression characteristic of sarcoidosis, NSOI, or granulomatosis with polyangiitis. Unsupervised cluster dendrograms further indicated the similarity between TED and healthy controls. Heat maps based on gene expression for cytokines, chemokines, or their receptors showed that these inflammatory markers were associated with NSOI, sarcoidosis, or GPA much more frequently than with TED. Conclusion This is the first study to compare gene expression in TED to gene expression associated with other causes of exophthalmos. The juxtaposition shows that inflammatory markers are far less characteristic of TED relative to other orbital inflammatory diseases. PMID:26371757

Quantitative polarization and flow evaluation of choroid and sclera by multifunctional Jones matrix optical coherence tomography

NASA Astrophysics Data System (ADS)

Sugiyama, S.; Hong, Y.-J.; Kasaragod, D.; Makita, S.; Miura, M.; Ikuno, Y.; Yasuno, Y.

2016-03-01

Quantitative evaluation of optical properties of choroid and sclera are performed by multifunctional optical coherence tomography. Five normal eyes, five glaucoma eyes and one choroidal atrophy eye are examined. The refractive error was found to be correlated with choroidal birefringence, polarization uniformity, and flow in addition to scleral birefringence among normal eyes. The significant differences were observed between the normal and the glaucoma eyes, as for choroidal polarization uniformity, flow and scleral birefringence. An automatic segmentation algorithm of retinal pigment epithelium and chorioscleral interface based on multifunctional signals is also presented.

Meta-analysis of Pentacam vs. ultrasound pachymetry in central corneal thickness measurement in normal, post-LASIK or PRK, and keratoconic or keratoconus-suspect eyes.

PubMed

Wu, Wenjing; Wang, Yan; Xu, Lulu

2014-01-01

The aim of this meta-analysis is to evaluate the central corneal thickness (CCT) measurement differences between Pentacam (Oculus Inc., Germany) and Ultrasound Pachymetry (USP) in normal (unoperated eyes , myopic and astigmatic eyes without corneal disease or topographic irregularity), after laser in situ keratomileusis (LASIK) or photorefractive keratectomy (PRK), and keratoconic or keratoconus suspected eyes. We assess whether Pentacam and USP have similar CCT differences in normal, thinner corneas after LASIK or PRK procedures, and kerotoconic or keratoconus suspected eyes. Data sources, including PubMed, Medline, EMBASE, and Cochrane Central Registry of Controlled Trials on the Cochrane Library, were searched to find the relevant studies. Primary outcome measures were CCT measurement between Pentacam and USP. Three groups of eyes were analyzed: normal; LASIK or PRK eyes; and keratoconus suspected or keratoconic eyes. Nineteen studies describing 1,908 eyes were enrolled in the normal group. Pentacam results were 1.47 μm ,95 % confidence interval (CI) -2.32 to 5.27, higher than USP without statistically significant difference (P = 0.45). Nine studies with total 539 eyes were included in the corneas after LASIK or PRK. The mean difference in the CCT measurement with Pentacam and ultrasound pachymetry was 1.03 μm, with the 95 % CI -3.36 to 5.42, there was no statistically difference (P = 0.64). Four studies with a total of 185 eyes were included in the keratoconic eyes or keratoconus-suspect group, however,the mean difference was -6.33 μm (95 % CI -9.17 to-3.49), which was statistically different between Pentacam and ultrasound pachymetry in the CCT measurement (P < 0.0001). Pentacam offers similar CCT results to ultrasound pachymetry in normal eyes, thinner corneas after LASIK or PRK procedures. However, in keratoconic or keratoconus-suspect eyes, Pentacam slightly underestimates the central corneal thickness than does ultrasound pachymetry, which may result from the difficulty in fixation of keratoconic eyes, misalignment of Pentacam and the variation of ultrasonic velocity due to the histological deformation.

Empirical evaluation of data normalization methods for molecular classification

PubMed Central

Huang, Huei-Chung

2018-01-01

Background Data artifacts due to variations in experimental handling are ubiquitous in microarray studies, and they can lead to biased and irreproducible findings. A popular approach to correct for such artifacts is through post hoc data adjustment such as data normalization. Statistical methods for data normalization have been developed and evaluated primarily for the discovery of individual molecular biomarkers. Their performance has rarely been studied for the development of multi-marker molecular classifiers—an increasingly important application of microarrays in the era of personalized medicine. Methods In this study, we set out to evaluate the performance of three commonly used methods for data normalization in the context of molecular classification, using extensive simulations based on re-sampling from a unique pair of microRNA microarray datasets for the same set of samples. The data and code for our simulations are freely available as R packages at GitHub. Results In the presence of confounding handling effects, all three normalization methods tended to improve the accuracy of the classifier when evaluated in an independent test data. The level of improvement and the relative performance among the normalization methods depended on the relative level of molecular signal, the distributional pattern of handling effects (e.g., location shift vs scale change), and the statistical method used for building the classifier. In addition, cross-validation was associated with biased estimation of classification accuracy in the over-optimistic direction for all three normalization methods. Conclusion Normalization may improve the accuracy of molecular classification for data with confounding handling effects; however, it cannot circumvent the over-optimistic findings associated with cross-validation for assessing classification accuracy. PMID:29666754

Alterations in Protein Expression in Tree Shrew Sclera during Development of Lens-Induced Myopia and Recovery

PubMed Central

Norton, Thomas T.

2012-01-01

Purpose. During the development of, and recovery from, negative lens-induced myopia there is regulated remodeling of the scleral extracellular matrix (ECM) that controls the extensibility of the sclera. Difference gel electrophoresis (DIGE) was used to identify and categorize proteins whose levels are altered in this process. Methods. Two groups of five tree shrews started monocular lens wear 24 days after eye opening (days of visual experience [VE]). The lens-induced myopia (LIM) group wore a −5 D lens for 4 days. The recovery (REC) group wore a −5 D lens for 11 days and then recovered for 4 days. Two normal groups (28 and 39 days of VE; n = 5 each) were also examined, age-matched to each of the treatment groups. Refractive and A-scan measures confirmed the effect of the treatments. Scleral proteins were isolated and resolved by DIGE. Proteins that differed in abundance were identified by mass spectrometry. Ingenuity pathway analysis was used to investigate potential biological pathway interactions. Results. During normal development (28–39 days of VE), eight proteins decreased and one protein increased in relative abundance. LIM-treated eyes were myopic and longer than control eyes; LIM-control eyes were slightly myopic compared with 28N eyes, indicating a yoking effect. In both the LIM-treated and the LIM-control eyes, there was a general downregulation from normal of proteins involved in transcription, cell adhesion, and protein synthesis. Additional proteins involved in cell adhesion, actin cytoskeleton, transcriptional regulation, and ECM structural proteins differed in the LIM-treated eyes versus normal but did not differ in the control eyes versus normal. REC-treated eyes were recovering from the induced myopia. REC-control eye refractions were not significantly different from the 39N eyes, and few proteins differed from age-matched normal eyes. The balance of protein expression in the REC-treated eyes, compared with normal eyes and REC-control eyes, shifted toward upregulation or a return to normal levels of proteins involved in cell adhesion, cell division, cytoskeleton, and ECM structural proteins, including upregulation of several cytoskeleton-related proteins not affected during myopia development. Conclusions. The DIGE procedure revealed new proteins whose abundance is altered during myopia development and recovery. Many of these are involved in cell-matrix adhesions, cytoskeleton, and transcriptional regulation and extend our understanding of the remodeling that controls the extensibility of the sclera. Reductions in these proteins during minus lens wear may produce the increased scleral viscoelasticity that results in faster axial elongation. Recovery is not a mirror image of lens-induced myopia—many protein levels, decreased during LIM, returned to normal, or slightly above normal, and additional cytoskeleton proteins were upregulated. However, no single protein or pathway appeared to be responsible for the scleral changes during myopia development or recovery. PMID:22039233

Evaluation of corneal biomechanics in patients with keratectasia following LASIK using dynamic Scheimpflug analyzer.

PubMed

Ueki, Ryotaro; Maeda, Naoyuki; Fuchihata, Mutsumi; Asai, Tomoko; Koh, Shizuka; Fujimoto, Hisataka; Uematsu, Masafumi; Nishida, Kohji

2018-04-26

To investigate the corneal biomechanics in eyes with keratectasia following LASIK using a dynamic Scheimpflug analyzer. Case-Control study. The subjects in the study included 12 eyes with keratectasia after LASIK (KE), 24 eyes with keratoconus (KC), 17 eyes without keratectasia after LASIK (LASIK), and 34 eyes with normal corneas (Normal). Corneal biomechanics of the four groups were evaluated using a dynamic Scheimpflug analyzer. Compared with Normal (7.06 ± 0.54), the radius at the highest concavity (radius, mm) of LASIK (5.96 ± 0.76), KE (4.93 ± 0.61) and KC (5.39 ± 1.02) were significantly small. The Deflection Amplitude (HCDLA, mm) of Normal (0.94 ± 0.07) was significantly lower than those of KE (1.11 ± 0.10) and KC (1.06 ± 0.16), and was not significantly different from that of LASIK (0.98 ± 0.07). There were significant differences between LASIK and KE in radius and HCDLA (P < 0.05), whereas KE and KC had no differences in these parameters. Corneal biomechanical features evaluated using the dynamic Scheimpflug analyzer suggest that biomechanical properties in eyes with keratectasia, keratoconus, and LASIK are different from those of normal eyes. Although the biomechanics in eyes with keratectasia differs from that in eyes with LASIK, it is similar to that in eyes with keratoconus.

Evaluation of Dry Eye and Meibomian Gland Dysfunction in Teenagers with Myopia through Noninvasive Keratograph

PubMed Central

Wang, Xiu; Lu, Xiaoxiao; Yang, Jun; Wei, Ruihua; Yang, Liyuan; Zhao, Shaozhen; Wang, Xilian

2016-01-01

Purpose. This study aims to evaluate dry eye and ocular surface conditions of myopic teenagers by using questionnaire and clinical examinations. Methods. A total of 496 eyes from 248 myopic teenagers (7–18 years old) were studied. We administered Ocular Surface Disease Index (OSDI) questionnaire, slit-lamp examination, and Keratograph 5M. The patients were divided into 2 groups based on OSDI dry eye standard, and their ocular surfaces and meibomian gland conditions were evaluated. Results. The tear meniscus heights of the dry eye and normal groups were in normal range. Corneal fluorescein scores were significantly higher whereas noninvasive break-up time was dramatically shorter in the dry eye group than in the normal group. All three meibomian gland dysfunction parameters (i.e., meibomian gland orifice scores, meibomian gland secretion scores, and meibomian gland dropout scores) of the dry eye group were significantly higher than those of the normal group (P < 0.0001). Conclusions. The prevalence of dry eye in myopic teenagers is 18.95%. Meibomian gland dysfunction plays an important role in dry eye in myopic teenagers. The Keratograph 5M appears to provide an effective noninvasive method for assessing ocular surface situation of myopic teenagers. PMID:26881059

Cognitive processing of orientation discrimination in anisometropic amblyopia.

PubMed

Wang, Jianglan; Zhao, Jiao; Wang, Shoujing; Gong, Rui; Zheng, Zhong; Liu, Longqian

2017-01-01

Cognition is very important in our daily life. However, amblyopia has abnormal visual cognition. Physiological changes of the brain during processes of cognition could be reflected with ERPs. So the purpose of this study was to investigate the speed and the capacity of resource allocation in visual cognitive processing in orientation discrimination task during monocular and binocular viewing conditions of amblyopia and normal control as well as the corresponding eyes of the two groups with ERPs. We also sought to investigate whether the speed and the capacity of resource allocation in visual cognitive processing vary with target stimuli at different spatial frequencies (3, 6 and 9 cpd) in amblyopia and normal control as well as between the corresponding eyes of the two groups. Fifteen mild to moderate anisometropic amblyopes and ten normal controls were recruited. Three-stimulus oddball paradigms of three different spatial frequency orientation discrimination tasks were used in monocular and binocular conditions in amblyopes and normal controls to elicit event-related potentials (ERPs). Accuracy (ACC), reaction time (RT), the latency of novelty P300 and P3b, and the amplitude of novelty P300 and P3b were measured. Results showed that RT was longer in the amblyopic eye than in both eyes of amblyopia and non-dominant eye in control. Novelty P300 amplitude was largest in the amblyopic eye, followed by the fellow eye, and smallest in both eyes of amblyopia. Novelty P300 amplitude was larger in the amblyopic eye than non-dominant eye and was larger in fellow eye than dominant eye. P3b latency was longer in the amblyopic eye than in the fellow eye, both eyes of amblyopia and non-dominant eye of control. P3b latency was not associated with RT in amblyopia. Neural responses of the amblyopic eye are abnormal at the middle and late stages of cognitive processing, indicating that the amblyopic eye needs to spend more time or integrate more resources to process the same visual task. Fellow eye and both eyes in amblyopia are slightly different from the dominant eye and both eyes in normal control at the middle and late stages of cognitive processing. Meanwhile, abnormal extents of amblyopic eye do not vary with three different spatial frequencies used in our study.

Cognitive processing of orientation discrimination in anisometropic amblyopia

PubMed Central

Wang, Jianglan; Zhao, Jiao; Wang, Shoujing; Gong, Rui; Zheng, Zhong; Liu, Longqian

2017-01-01

Cognition is very important in our daily life. However, amblyopia has abnormal visual cognition. Physiological changes of the brain during processes of cognition could be reflected with ERPs. So the purpose of this study was to investigate the speed and the capacity of resource allocation in visual cognitive processing in orientation discrimination task during monocular and binocular viewing conditions of amblyopia and normal control as well as the corresponding eyes of the two groups with ERPs. We also sought to investigate whether the speed and the capacity of resource allocation in visual cognitive processing vary with target stimuli at different spatial frequencies (3, 6 and 9 cpd) in amblyopia and normal control as well as between the corresponding eyes of the two groups. Fifteen mild to moderate anisometropic amblyopes and ten normal controls were recruited. Three-stimulus oddball paradigms of three different spatial frequency orientation discrimination tasks were used in monocular and binocular conditions in amblyopes and normal controls to elicit event-related potentials (ERPs). Accuracy (ACC), reaction time (RT), the latency of novelty P300 and P3b, and the amplitude of novelty P300 and P3b were measured. Results showed that RT was longer in the amblyopic eye than in both eyes of amblyopia and non-dominant eye in control. Novelty P300 amplitude was largest in the amblyopic eye, followed by the fellow eye, and smallest in both eyes of amblyopia. Novelty P300 amplitude was larger in the amblyopic eye than non-dominant eye and was larger in fellow eye than dominant eye. P3b latency was longer in the amblyopic eye than in the fellow eye, both eyes of amblyopia and non-dominant eye of control. P3b latency was not associated with RT in amblyopia. Neural responses of the amblyopic eye are abnormal at the middle and late stages of cognitive processing, indicating that the amblyopic eye needs to spend more time or integrate more resources to process the same visual task. Fellow eye and both eyes in amblyopia are slightly different from the dominant eye and both eyes in normal control at the middle and late stages of cognitive processing. Meanwhile, abnormal extents of amblyopic eye do not vary with three different spatial frequencies used in our study. PMID:29023501

Choroidal thickness in Chinese patients with non-arteritic anterior ischemic optic neuropathy.

PubMed

Jiang, Libin; Chen, Lanlan; Qiu, Xiujuan; Jiang, Ran; Wang, Yaxing; Xu, Liang; Lai, Timothy Y Y

2016-08-31

Non-arteritic anterior ischemic optic neuropathy (NA-AION) is one of the most common types of ischemic optic neuropathy. Several recent studies suggested that abnormalities of choroidal thickness might be associated with NA-AION. The main objective of this case-control study was to evaluate whether choroidal thickness is an ocular risk factor for the development of NA-AION by evaluating the peripapillary and subfoveal choroidal thicknesses in affected Chinese patients. Forty-four Chinese patients with unilateral NA-AION were recruited and compared with 60 eyes of 60 normal age and refractive-error matched control subjects. Peripapillary and subfoveal choroidal thicknesses were measured by enhanced depth imaging optical coherence tomography. Choroidal thicknesses of eyes with NA-AION and unaffected fellow eyes were compared with normal controls. Choroidal thicknesses of NA-AION eyes with or without optic disc edema were also compared. The correlation between choroidal thickness and retinal nerve fiber layer (RNFL) thickness, logMAR best-corrected visual acuity (BCVA), and the mean deviation (MD) of Humphrey static perimetry in NA-AION eyes were analyzed. The peripapillary choroidal thicknesses at the nasal, nasal inferior and temporal inferior segments in NA-AION eyes with optic disc edema were significantly thicker compared with that of normal subjects (P < 0.05). There was no significant difference in the choroidal thicknesses between the unaffected fellow eyes of NA-AION patients and normal eyes of healthy controls; or between the NA-AION eyes with resolved optic disc edema and normal eyes (all P > 0.05). No significant correlation between choroidal thickness and RNFL thickness, logMAR BCVA and perimetry MD was found in eyes affected by NA-AION (all P > 0.05). Increase in peripapillary choroid thickness in some segments was found in NA-ION eyes with optic disc edema. However, our findings do not support the hypothesis that choroidal thickness is abnormal in Chinese patients with NA-AION compared with normal subjects with similar age and refractive error status.

A preliminary investigation into the effects of ocular lubricants on higher order aberrations in normal and dry eye subjects.

PubMed

McGinnigle, Samantha; Eperjesi, Frank; Naroo, Shehzad A

2014-04-01

To study the effects of ocular lubricants on higher order aberrations in normal and self-diagnosed dry eyes. Unpreserved hypromellose drops, Tears Again™ liposome spray and a combination of both were administered to the right eye of 24 normal and 24 dry eye subjects following classification according to a 5 point questionnaire. Total ocular higher order aberrations, coma, spherical aberration and Strehl ratios for higher order aberrations were measured using the Nidek OPD-Scan III (Nidek Technologies, Gamagori, Japan) at baseline, immediately after application and after 60 min. The aberration data were analyzed over a 5mm natural pupil using Zernike polynomials. Each intervention was assessed on a separate day and comfort levels were recorded before and after application. Corneal staining was assessed and product preference recorded after the final measurement for each intervention. Hypromellose drops caused an increase in total higher order aberrations (p=<0.01 in normal and dry eyes) and a reduction in Strehl ratio (normal eyes: p=<0.01, dry eyes p=0.01) immediately after instillation. There were no significant differences between normal and self-diagnosed dry eyes for response to intervention and no improvement in visual quality or reduction in higher order aberrations after 60 min. Differences in comfort levels failed to reach statistical significance. Combining treatments does not offer any benefit over individual treatments in self-diagnosed dry eyes and no individual intervention reached statistical significance. Symptomatic subjects with dry eye and no corneal staining reported an improvement in comfort after using lubricants. Copyright © 2013 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.

Time course of dichoptic masking in normals and suppression in amblyopes.

PubMed

Zhou, Jiawei; McNeal, Suzanne; Babu, Raiju J; Baker, Daniel H; Bobier, William R; Hess, Robert F

2014-04-17

To better understand the relationship between dichoptic masking in normal vision and suppression in amblyopia we address three questions: First, what is the time course of dichoptic masking in normals and amblyopes? Second, is interocular suppression low-pass or band-pass in its spatial dependence? And third, in the above two regards, is dichoptic masking in normals different from amblyopic suppression? We measured the dependence of dichoptic masking in normal controls and amblyopes on the temporal duration of presentation under three conditions; monocular (the nontested eye-i.e., dominant eye of normals or nonamblyopic eye of amblyopes, being patched), dichoptic-luminance (the nontested eye seeing a mean luminance-i.e., a DC component) and dichoptic-contrast (the nontested eye seeing high-contrast visual noise). The subject had to detect a letter in the other eye, the contrast of which was varied. We found that threshold elevation relative to the patched condition occurred in both normals and amblyopes when the nontested eye saw either 1/f or band-pass filtered noise, but not just mean luminance (i.e., there was no masking from the DC component that corresponds to a channel responsive to a spatial frequency of 0 cyc/deg); longer presentation of the target (corresponding to lower temporal frequencies) produced greater threshold elevation. Dichoptic masking exhibits similar properties in both subject groups, being low-pass temporally and band-pass spatially, so that masking was greatest at the longest presentation durations and was not greatly affected by mean luminance in the nontested eye. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

Optical aberrations, retinal image quality and eye growth: Experimentation and modeling

NASA Astrophysics Data System (ADS)

Tian, Yibin

2007-12-01

Retinal image quality is important for normal eye growth. Optical aberrations are of interest for two reasons: first, they degrade retinal images; second, they might provide some cues to defocus. Higher than normal ocular aberrations have been previously associated with human myopia. However, these studies were cross-sectional in design, and only reported aberrations in terms of root mean square (RMS) errors of Zernike coefficients, a poor metric of optical quality. This dissertation presents results from investigations of ocular optical aberrations, retinal image quality and eye growth in chicks and humans. A number of techniques were utilized, including Shack-Hartmann aberrometry, high-frequency A-scan ultrasonography, ciliary nerve section (CNX), photorefractive keratectomy (PRK) as well as computer simulations and modeling. A technique to extract light scatter information from Shack-Hartmann images was also developed. The main findings of the dissertation are summarized below. In young chicks, most ocular aberrations decreased with growth in both normal and CNX eyes, and there were diurnal fluctuations in some aberrations. Modeling suggested active reduction in higher order aberrations (HOAs) during early development. Although CNX eyes manifested greater than normal HOAs, they showed near normal growth. Retinal image degradation varied greatly among individual eyes post-PRK in young chicks. Including light scatter information into analyses of retinal image quality better estimated the latter. Albino eyes showed more severe retinal image degradation than normal eyes, due to increased optical aberrations and light scatter, but their growth was similar to those of normal eyes, implying that they are relatively insensitive to retina image quality. Although the above results questioned the influence of optical aberrations on early ocular growth, some optical quality metrics, derived from optical aberrations data, could predict how much the eyes of young chicks subsequently elongated. The performance of some focus measures was very poor when non-defocus aberrations exceeded a certain level; presumably, these non-defocus aberrations might interfere with the eye's ability to interpret defocus. In anisomyopic human adults, more myopic eyes had larger anterior and vitreous chambers, greater astigmatism, and more positive spherical aberration. However, compared to isometropes, only interocular differences in spherical equivalent refractive errors were significantly increased.

Effect of spectrum bias on the diagnostic accuracy of spectral-domain optical coherence tomography in glaucoma.

PubMed

Rao, Harsha L; Kumbar, Tukaram; Addepalli, Uday K; Bharti, Neha; Senthil, Sirisha; Choudhari, Nikhil S; Garudadri, Chandra S

2012-02-29

To evaluate the influence of a control group on the diagnostic accuracy of spectral-domain optical coherence tomography (SD-OCT) in early glaucoma. In a diagnostic, case-control study, 119 eyes of 60 normal subjects with no findings suspicious for glaucoma (control cohort 1); 76 eyes of 41 subjects referred by general ophthalmologists as glaucoma suspects based on optic disc morphology, but found by glaucoma experts to be normal but with physiological variations in their optic nerves (control cohort 2); and 65 eyes of 46 early-glaucoma patients (cases) underwent imaging of the optic nerve head (ONH), retinal nerve fiber layer (RNFL), and ganglion cell complex (GCC) by SD-OCT. Areas under the receiver operating characteristic curves (AUC) of ONH parameters discriminating glaucomatous eyes from normal eyes of control cohort 2 were significantly lesser (P < 0.001) than those discriminating glaucomatous eyes from normal eyes of control cohort 1. AUCs of RNFL parameters discriminating glaucomatous eyes from normal eyes of control cohorts 2 and 1 were comparable. Although the AUCs of GCC thickness parameters were comparable, AUCs of GCC focal and global loss volume in control cohort 2 (0.684 and 0.671. respectively) were significantly less (P < 0.05) than in control cohort 1 (0.881 and 0.841, respectively). The effectiveness of most SD-OCT parameters in detecting glaucoma significantly decreased when evaluated against a clinically relevant control group with suspicious-looking optic nerves compared with that against a control group consisting of normal subjects with no findings suspicious for glaucoma.

Upregulated epidermal growth factor receptor expression following near-infrared irradiation simulating solar radiation in a three-dimensional reconstructed human corneal epithelial tissue culture model

PubMed Central

Tanaka, Yohei; Nakayama, Jun

2016-01-01

Background and objective Humans are increasingly exposed to near-infrared (NIR) radiation from both natural (eg, solar) and artificial (eg, electrical appliances) sources. Although the biological effects of sun and ultraviolet (UV) exposure have been extensively investigated, the biological effect of NIR radiation is still unclear. We previously reported that NIR as well as UV induces photoaging and standard UV-blocking materials, such as sunglasses, do not sufficiently block NIR. The objective of this study was to investigate changes in gene expression in three-dimensional reconstructed corneal epithelial tissue culture exposed to broad-spectrum NIR irradiation to simulate solar NIR radiation that reaches human tissues. Materials and methods DNA microarray and quantitative real-time polymerase chain reaction analysis were used to assess gene expression levels in a three-dimensional reconstructed corneal epithelial model composed of normal human corneal epithelial cells exposed to water-filtered broad-spectrum NIR irradiation with a contact cooling (20°C). The water-filter allowed 1,000–1,800 nm wavelengths and excluded 1,400–1,500 nm wavelengths. Results A DNA microarray with >62,000 different probes showed 25 and 150 genes that were up- or downregulated by at least fourfold and twofold, respectively, after NIR irradiation. In particular, epidermal growth factor receptor (EGFR) was upregulated by 19.4-fold relative to control cells. Quantitative real-time polymerase chain reaction analysis revealed that two variants of EGFR in human corneal epithelial tissue were also significantly upregulated after five rounds of 10 J/cm2 irradiation (P<0.05). Conclusion We found that NIR irradiation induced the upregulated expression of EGFR in human corneal cells. Since over half of the solar energy reaching the Earth is in the NIR region, which cannot be adequately blocked by eyewear and thus can induce eye damage with intensive or long-term exposure, protection from both UV and NIR radiation may prevent changes in gene expression and in turn eye damage. PMID:27536083

Wavefront-Guided Scleral Lens Correction in Keratoconus

PubMed Central

Marsack, Jason D.; Ravikumar, Ayeswarya; Nguyen, Chi; Ticak, Anita; Koenig, Darren E.; Elswick, James D.; Applegate, Raymond A.

2014-01-01

Purpose To examine the performance of state-of-the-art wavefront-guided scleral contact lenses (wfgSCLs) on a sample of keratoconic eyes, with emphasis on performance quantified with visual quality metrics; and to provide a detailed discussion of the process used to design, manufacture and evaluate wfgSCLs. Methods Fourteen eyes of 7 subjects with keratoconus were enrolled and a wfgSCL was designed for each eye. High-contrast visual acuity and visual quality metrics were used to assess the on-eye performance of the lenses. Results The wfgSCL provided statistically lower levels of both lower-order RMS (p < 0.001) and higher-order RMS (p < 0.02) than an intermediate spherical equivalent scleral contact lens. The wfgSCL provided lower levels of lower-order RMS than a normal group of well-corrected observers (p < < 0.001). However, the wfgSCL does not provide less higher-order RMS than the normal group (p = 0.41). Of the 14 eyes studied, 10 successfully reached the exit criteria, achieving residual higher-order root mean square wavefront error (HORMS) less than or within 1 SD of the levels experienced by normal, age-matched subjects. In addition, measures of visual image quality (logVSX, logNS and logLIB) for the 10 eyes were well distributed within the range of values seen in normal eyes. However, visual performance as measured by high contrast acuity did not reach normal, age-matched levels, which is in agreement with prior results associated with the acute application of wavefront correction to KC eyes. Conclusions Wavefront-guided scleral contact lenses are capable of optically compensating for the deleterious effects of higher-order aberration concomitant with the disease, and can provide visual image quality equivalent to that seen in normal eyes. Longer duration studies are needed to assess whether the visual system of the highly aberrated eye wearing a wfgSCL is capable of producing visual performance levels typical of the normal population. PMID:24830371

Gold nanoparticle‐based brachytherapy enhancement in choroidal melanoma using a full Monte Carlo model of the human eye

PubMed Central

Vaez‐zadeh, Mehdi; Masoudi, S. Farhad; Rahmani, Faezeh; Knaup, Courtney; Meigooni, Ali S.

2015-01-01

The effects of gold nanoparticles (GNPs) in 125I brachytherapy dose enhancement on choroidal melanoma are examined using the Monte Carlo simulation technique. Usually, Monte Carlo ophthalmic brachytherapy dosimetry is performed in a water phantom. However, here, the compositions of human eye have been considered instead of water. Both human eye and water phantoms have been simulated with MCNP5 code. These simulations were performed for a fully loaded 16 mm COMS eye plaque containing 13 125I seeds. The dose delivered to the tumor and normal tissues have been calculated in both phantoms with and without GNPs. Normally, the radiation therapy of cancer patients is designed to deliver a required dose to the tumor while sparing the surrounding normal tissues. However, as the normal and cancerous cells absorbed dose in an almost identical fashion, the normal tissue absorbed radiation dose during the treatment time. The use of GNPs in combination with radiotherapy in the treatment of tumor decreases the absorbed dose by normal tissues. The results indicate that the dose to the tumor in an eyeball implanted with COMS plaque increases with increasing GNPs concentration inside the target. Therefore, the required irradiation time for the tumors in the eye is decreased by adding the GNPs prior to treatment. As a result, the dose to normal tissues decreases when the irradiation time is reduced. Furthermore, a comparison between the simulated data in an eye phantom made of water and eye phantom made of human eye composition, in the presence of GNPs, shows the significance of utilizing the composition of eye in ophthalmic brachytherapy dosimetry Also, defining the eye composition instead of water leads to more accurate calculations of GNPs radiation effects in ophthalmic brachytherapy dosimetry. PACS number: 87.53.Jw, 87.85.Rs, 87.10.Rt PMID:26699318

Comparison of objective optical quality measured by double-pass aberrometry in patients with moderate dry eye: Normal saline vs. artificial tears: A pilot study.

PubMed

Vandermeer, G; Chamy, Y; Pisella, P-J

2018-02-01

Dry eye is defined by a tear film instability resulting in variable but systematic fluctuations in quality of vision. Variability in optical quality can be demonstrated using a double pass aberrometer such as the Optical Quality Analyzing System, Visiometrics (OQAS). The goal of this work is to compare fluctuations in objective quality of vision measured by OQAS between treatment with normal saline eye drops and treatment with carmellose 0.5% and hyaluronic acid 0.1% (Optive Fusion [OF], Allergan) in patients with moderate dry eye syndrome. Optical quality was measured by evaluating the variations in the Optical Scattering Index (OSI) over 20seconds using the OQAS. Inclusion criteria were dry eye syndrome with an ocular surface disease index (OSDI) score >23 treated only with artificial tears. The patients were their own controls: OF in one eye and normal saline in the fellow eye. The choice of the subject eye and control eye was determined in a randomized fashion. OSI variations were measured in each eye before instillation, 5minutes and 2hours after instillation. The primary endpoint was OSI fluctuation over 20seconds of measurement. Secondary endpoints were the number of blinks and patient preference (preferred eye). Preliminary results were obtained on 19 patients. Average OSDI score was 36.8. Visual acuity was 10/10 with no significant difference between the two eyes. Prior to instillation, there was no significant difference between "normal saline" and "OF" eyes in terms of OSI, OSI variability or number of blinks. In the normal saline eye, there were no significant variations in mean OSI, OSI variability, OSI slope, or number of blinks. However, in the "OF" eye, there was a significant variation between initial and 2-hour OSI variability (0.363 versus 0.204, P<0.05), the average slope of OSI (0.04 versus 0.01, P<0.05) and the number of blinks (4.2 versus 2.8, P<0.05). Among the patients, 65% preferred the OF eye, 24% did not have a preference, and 11% preferred the normal saline eye. Objective quality of vision measured by OQAS is an interesting parameter for evaluating the effectiveness of a lacrimal substitute. The purpose of artificial tears is, among other things, to provide comfort and a reduction of dry eye symptoms such as poor quality of vision. This study demonstrates that 0.5% carmellose and 0.1% hyaluronic acid allowed better stabilization of the tear film and thus a significant improvement in the quality of vision compared to normal saline. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

[Comparison of objective optical quality measured by double-pass aberrometry in patients with moderate dry eye: Normal saline vs. artificial tears: A pilot study].

PubMed

Vandermeer, G; Chamy, Y; Pisella, P-J

2018-03-01

Dry eye is defined by a tear film instability resulting in variable but systematic fluctuations in the quality of vision. Variability in optical quality can be demonstrated using a double pass aberrometer such as the OQAS (Optical Quality Analyzing System, Visiometrics). The goal of this work is to compare fluctuations in objective quality of vision measured by OQAS between treatment with normal saline eye drops and treatment with carmellose 0.5% and hyaluronic acid 0.1% (Optive Fusion [OF], Allergan) in patients with moderate dry eye syndrome. Optical quality was measured by evaluating the variations in the Optical Scattering Index (OSI) over 20seconds using the OQAS. Inclusion criteria were dry eye syndrome with an Ocular Surface Disease Index (OSDI) score>23 treated only with artificial tears. The patients were their own controls: OF in one eye and normal saline in the fellow eye. The choice of the subject eye and control eye was determined in a randomized fashion. OSI variations were measured in each eye before instillation, 5minutes and 2hours after instillation. The primary endpoint was OSI fluctuation over 20seconds of measurement. Secondary endpoints were the number of blinks and patient's preference (preferred eye). Preliminary results were obtained on 19 patients. Average OSDI score was 36.8. Visual acuity was 10/10 with no significant difference between the two eyes. Prior to instillation, there was no significant difference between "normal saline" and "OF" eyes in terms of OSI, OSI variability or number of blinks. In the normal saline eye, there was no significant variation in mean OSI, OSI variability, OSI slope, or number of blinks. However, in the "OF" eye, there was a significant variation between initial and 2-hour OSI variability (0.363 versus 0.204; P<0.05), the average slope of OSI (0.04 versus 0.01; P<0.05) and the number of blinks (4.2 versus 2.8; P<0.05). Sixty-five percent of patients preferred the OF eye, 24% did not have a preference, and 11% preferred the normal saline eye. Objective quality of vision measured by OQAS is an interesting parameter for evaluating the effectiveness of a lacrimal substitute. The purpose of artificial tears is, among other things, to provide comfort and a reduction of dry eye symptoms such as poor quality of vision. This study demonstrates that 0.5% carmellose and 0.1% hyaluronic acid allowed better stabilization of the tear film and thus a significant improvement in the quality of vision compared to normal saline. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

A new experimental device to evaluate eye ulcers using a multispectral electrical impedance technique

NASA Astrophysics Data System (ADS)

Bellotti, Mariela I.; Bast, Walter; Berra, Alejandro; Bonetto, Fabián J.

2011-07-01

We present a novel experimental technique to determine eye ulcers in animals using a spectral electrical impedance technique. We expect that this technique will be useful in dry eye syndrome. We used a sensor that is basically a platinum (Pt) microelectrode electrically insulated by glass from a cylindrical stainless steel counter-electrode. This sensor was applied to the naked eye of New Zealand rabbits (2.0-3.5 kg in weight). Whereas half of the eyes were normal (control), we applied to the remainder a few drops of 20% (v/v) alcohol to produce an ulcer in the eye. Using a multispectral electrical impedance system we measured ulcerated and control eyes and observed significant difference between normal and pathological samples. We also investigated the effects of different applied pressures and natural degradation of initially normal eyes as a function of time. We believe that this technique could be sufficiently sensitive and repetitive to help diagnose ocular surface diseases such as dry eye syndrome.

A new experimental device to evaluate eye ulcers using a multispectral electrical impedance technique.

PubMed

Bellotti, Mariela I; Bast, Walter; Berra, Alejandro; Bonetto, Fabián J

2011-07-01

We present a novel experimental technique to determine eye ulcers in animals using a spectral electrical impedance technique. We expect that this technique will be useful in dry eye syndrome. We used a sensor that is basically a platinum (Pt) microelectrode electrically insulated by glass from a cylindrical stainless steel counter-electrode. This sensor was applied to the naked eye of New Zealand rabbits (2.0-3.5 kg in weight). Whereas half of the eyes were normal (control), we applied to the remainder a few drops of 20% (v/v) alcohol to produce an ulcer in the eye. Using a multispectral electrical impedance system we measured ulcerated and control eyes and observed significant difference between normal and pathological samples. We also investigated the effects of different applied pressures and natural degradation of initially normal eyes as a function of time. We believe that this technique could be sufficiently sensitive and repetitive to help diagnose ocular surface diseases such as dry eye syndrome.

A python module to normalize microarray data by the quantile adjustment method.

PubMed

Baber, Ibrahima; Tamby, Jean Philippe; Manoukis, Nicholas C; Sangaré, Djibril; Doumbia, Seydou; Traoré, Sekou F; Maiga, Mohamed S; Dembélé, Doulaye

2011-06-01

Microarray technology is widely used for gene expression research targeting the development of new drug treatments. In the case of a two-color microarray, the process starts with labeling DNA samples with fluorescent markers (cyanine 635 or Cy5 and cyanine 532 or Cy3), then mixing and hybridizing them on a chemically treated glass printed with probes, or fragments of genes. The level of hybridization between a strand of labeled DNA and a probe present on the array is measured by scanning the fluorescence of spots in order to quantify the expression based on the quality and number of pixels for each spot. The intensity data generated from these scans are subject to errors due to differences in fluorescence efficiency between Cy5 and Cy3, as well as variation in human handling and quality of the sample. Consequently, data have to be normalized to correct for variations which are not related to the biological phenomena under investigation. Among many existing normalization procedures, we have implemented the quantile adjustment method using the python computer language, and produced a module which can be run via an HTML dynamic form. This module is composed of different functions for data files reading, intensity and ratio computations and visualization. The current version of the HTML form allows the user to visualize the data before and after normalization. It also gives the option to subtract background noise before normalizing the data. The output results of this module are in agreement with the results of other normalization tools. Published by Elsevier B.V.

Spotting effect in microarray experiments

PubMed Central

Mary-Huard, Tristan; Daudin, Jean-Jacques; Robin, Stéphane; Bitton, Frédérique; Cabannes, Eric; Hilson, Pierre

2004-01-01

Background Microarray data must be normalized because they suffer from multiple biases. We have identified a source of spatial experimental variability that significantly affects data obtained with Cy3/Cy5 spotted glass arrays. It yields a periodic pattern altering both signal (Cy3/Cy5 ratio) and intensity across the array. Results Using the variogram, a geostatistical tool, we characterized the observed variability, called here the spotting effect because it most probably arises during steps in the array printing procedure. Conclusions The spotting effect is not appropriately corrected by current normalization methods, even by those addressing spatial variability. Importantly, the spotting effect may alter differential and clustering analysis. PMID:15151695

Variation of gene expression in Bacillus subtilis samples of fermentation replicates.

PubMed

Zhou, Ying; Yu, Wen-Bang; Ye, Bang-Ce

2011-06-01

The application of comprehensive gene expression profiling technologies to compare wild and mutated microorganism samples or to assess molecular differences between various treatments has been widely used. However, little is known about the normal variation of gene expression in microorganisms. In this study, an Agilent customized microarray representing 4,106 genes was used to quantify transcript levels of five-repeated flasks to assess normal variation in Bacillus subtilis gene expression. CV analysis and analysis of variance were employed to investigate the normal variance of genes and the components of variance, respectively. The results showed that above 80% of the total variation was caused by biological variance. For the 12 replicates, 451 of 4,106 genes exhibited variance with CV values over 10%. The functional category enrichment analysis demonstrated that these variable genes were mainly involved in cell type differentiation, cell type localization, cell cycle and DNA processing, and spore or cyst coat. Using power analysis, the minimal biological replicate number for a B. subtilis microarray experiment was determined to be six. The results contribute to the definition of the baseline level of variability in B. subtilis gene expression and emphasize the importance of replicate microarray experiments.

Comparison for aphasic and control subjects of eye movements hypothesized in neurolinguistic programming.

PubMed

Dooley, K O; Farmer, A

1988-08-01

Neurolinguistic programming's hypothesized eye movements were measured independently using videotapes of 10 nonfluent aphasic and 10 control subjects matched for age and sex. Chi-squared analysis indicated that eye-position responses were significantly different for the groups. Although earlier research has not supported the hypothesized eye positions for normal subjects, the present findings support the contention that eye-position responses may differ between neurologically normal and aphasic individuals.

Evaluation of normalization methods for cDNA microarray data by k-NN classification

PubMed Central

Wu, Wei; Xing, Eric P; Myers, Connie; Mian, I Saira; Bissell, Mina J

2005-01-01

Background Non-biological factors give rise to unwanted variations in cDNA microarray data. There are many normalization methods designed to remove such variations. However, to date there have been few published systematic evaluations of these techniques for removing variations arising from dye biases in the context of downstream, higher-order analytical tasks such as classification. Results Ten location normalization methods that adjust spatial- and/or intensity-dependent dye biases, and three scale methods that adjust scale differences were applied, individually and in combination, to five distinct, published, cancer biology-related cDNA microarray data sets. Leave-one-out cross-validation (LOOCV) classification error was employed as the quantitative end-point for assessing the effectiveness of a normalization method. In particular, a known classifier, k-nearest neighbor (k-NN), was estimated from data normalized using a given technique, and the LOOCV error rate of the ensuing model was computed. We found that k-NN classifiers are sensitive to dye biases in the data. Using NONRM and GMEDIAN as baseline methods, our results show that single-bias-removal techniques which remove either spatial-dependent dye bias (referred later as spatial effect) or intensity-dependent dye bias (referred later as intensity effect) moderately reduce LOOCV classification errors; whereas double-bias-removal techniques which remove both spatial- and intensity effect reduce LOOCV classification errors even further. Of the 41 different strategies examined, three two-step processes, IGLOESS-SLFILTERW7, ISTSPLINE-SLLOESS and IGLOESS-SLLOESS, all of which removed intensity effect globally and spatial effect locally, appear to reduce LOOCV classification errors most consistently and effectively across all data sets. We also found that the investigated scale normalization methods do not reduce LOOCV classification error. Conclusion Using LOOCV error of k-NNs as the evaluation criterion, three double-bias-removal normalization strategies, IGLOESS-SLFILTERW7, ISTSPLINE-SLLOESS and IGLOESS-SLLOESS, outperform other strategies for removing spatial effect, intensity effect and scale differences from cDNA microarray data. The apparent sensitivity of k-NN LOOCV classification error to dye biases suggests that this criterion provides an informative measure for evaluating normalization methods. All the computational tools used in this study were implemented using the R language for statistical computing and graphics. PMID:16045803

Evaluation of normalization methods for cDNA microarray data by k-NN classification.

PubMed

Wu, Wei; Xing, Eric P; Myers, Connie; Mian, I Saira; Bissell, Mina J

2005-07-26

Non-biological factors give rise to unwanted variations in cDNA microarray data. There are many normalization methods designed to remove such variations. However, to date there have been few published systematic evaluations of these techniques for removing variations arising from dye biases in the context of downstream, higher-order analytical tasks such as classification. Ten location normalization methods that adjust spatial- and/or intensity-dependent dye biases, and three scale methods that adjust scale differences were applied, individually and in combination, to five distinct, published, cancer biology-related cDNA microarray data sets. Leave-one-out cross-validation (LOOCV) classification error was employed as the quantitative end-point for assessing the effectiveness of a normalization method. In particular, a known classifier, k-nearest neighbor (k-NN), was estimated from data normalized using a given technique, and the LOOCV error rate of the ensuing model was computed. We found that k-NN classifiers are sensitive to dye biases in the data. Using NONRM and GMEDIAN as baseline methods, our results show that single-bias-removal techniques which remove either spatial-dependent dye bias (referred later as spatial effect) or intensity-dependent dye bias (referred later as intensity effect) moderately reduce LOOCV classification errors; whereas double-bias-removal techniques which remove both spatial- and intensity effect reduce LOOCV classification errors even further. Of the 41 different strategies examined, three two-step processes, IGLOESS-SLFILTERW7, ISTSPLINE-SLLOESS and IGLOESS-SLLOESS, all of which removed intensity effect globally and spatial effect locally, appear to reduce LOOCV classification errors most consistently and effectively across all data sets. We also found that the investigated scale normalization methods do not reduce LOOCV classification error. Using LOOCV error of k-NNs as the evaluation criterion, three double-bias-removal normalization strategies, IGLOESS-SLFILTERW7, ISTSPLINE-SLLOESS and IGLOESS-SLLOESS, outperform other strategies for removing spatial effect, intensity effect and scale differences from cDNA microarray data. The apparent sensitivity of k-NN LOOCV classification error to dye biases suggests that this criterion provides an informative measure for evaluating normalization methods. All the computational tools used in this study were implemented using the R language for statistical computing and graphics.

Binocular Summation and Other Forms of Non-Dominant Eye Contribution in Individuals with Strabismic Amblyopia during Habitual Viewing

PubMed Central

Barrett, Brendan T.; Panesar, Gurvinder K.; Scally, Andrew J.; Pacey, Ian E.

2013-01-01

Background Adults with amblyopia (‘lazy eye’), long-standing strabismus (ocular misalignment) or both typically do not experience visual symptoms because the signal from weaker eye is given less weight than the signal from its fellow. Here we examine the contribution of the weaker eye of individuals with strabismus and amblyopia with both eyes open and with the deviating eye in its anomalous motor position. Methodology/Results The task consisted of a blue-on-yellow detection task along a horizontal line across the central 50 degrees of the visual field. We compare the results obtained in ten individuals with strabismic amblyopia with ten visual normals. At each field location in each participant, we examined how the sensitivity exhibited under binocular conditions compared with sensitivity from four predictions, (i) a model of binocular summation, (ii) the average of the monocular sensitivities, (iii) dominant-eye sensitivity or (iv) non-dominant-eye sensitivity. The proportion of field locations for which the binocular summation model provided the best description of binocular sensitivity was similar in normals (50.6%) and amblyopes (48.2%). Average monocular sensitivity matched binocular sensitivity in 14.1% of amblyopes’ field locations compared to 8.8% of normals’. Dominant-eye sensitivity explained sensitivity at 27.1% of field locations in amblyopes but 21.2% in normals. Non-dominant-eye sensitivity explained sensitivity at 10.6% of field locations in amblyopes but 19.4% in normals. Binocular summation provided the best description of the sensitivity profile in 6/10 amblyopes compared to 7/10 of normals. In three amblyopes, dominant-eye sensitivity most closely reflected binocular sensitivity (compared to two normals) and in the remaining amblyope, binocular sensitivity approximated to an average of the monocular sensitivities. Conclusions Our results suggest a strong positive contribution in habitual viewing from the non-dominant eye in strabismic amblyopes. This is consistent with evidence from other sources that binocular mechanisms are frequently intact in strabismic and amblyopic individuals. PMID:24205005

The evaluation of eye pain with a normal ocular exam.

PubMed

Lee, Andrew G; Brazis, Paul W

2003-12-01

Eye pain with or without associated head or face pain is a common complaint to the ophthalmologist. The ocular exam may reveal the etiology (e.g., corneal disease, angle closure glaucoma) but typically the exam is normal. This paper reviews the evaluation and management of eye pain with a "normal" ocular exam, including: 1) subtle findings on ocular exam; 2) transient findings on exam, and 3) no abnormal ocular findings. Ophthalmologists should be aware of the various etiologies for eye pain and the specific and distinctive features that make the diagnosis.

Objective eye-gaze behaviour during face-to-face communication with proficient alaryngeal speakers: a preliminary study.

PubMed

Evitts, Paul; Gallop, Robert

2011-01-01

There is a large body of research demonstrating the impact of visual information on speaker intelligibility in both normal and disordered speaker populations. However, there is minimal information on which specific visual features listeners find salient during conversational discourse. To investigate listeners' eye-gaze behaviour during face-to-face conversation with normal, laryngeal and proficient alaryngeal speakers. Sixty participants individually participated in a 10-min conversation with one of four speakers (typical laryngeal, tracheoesophageal, oesophageal, electrolaryngeal; 15 participants randomly assigned to one mode of speech). All speakers were > 85% intelligible and were judged to be 'proficient' by two certified speech-language pathologists. Participants were fitted with a head-mounted eye-gaze tracking device (Mobile Eye, ASL) that calculated the region of interest and mean duration of eye-gaze. Self-reported gaze behaviour was also obtained following the conversation using a 10 cm visual analogue scale. While listening, participants viewed the lower facial region of the oesophageal speaker more than the normal or tracheoesophageal speaker. Results of non-hierarchical cluster analyses showed that while listening, the pattern of eye-gaze was predominantly directed at the lower face of the oesophageal and electrolaryngeal speaker and more evenly dispersed among the background, lower face, and eyes of the normal and tracheoesophageal speakers. Finally, results show a low correlation between self-reported eye-gaze behaviour and objective regions of interest data. Overall, results suggest similar eye-gaze behaviour when healthy controls converse with normal and tracheoesophageal speakers and that participants had significantly different eye-gaze patterns when conversing with an oesophageal speaker. Results are discussed in terms of existing eye-gaze data and its potential implications on auditory-visual speech perception. © 2011 Royal College of Speech & Language Therapists.

Temperatures of the Ocular Surface, Lid, and Periorbital Regions of Sjögren's, Evaporative, and Aqueous-Deficient Dry Eyes Relative to Normals.

PubMed

Abreau, Kerstin; Callan, Christine; Kottaiyan, Ranjini; Zhang, Aizhong; Yoon, Geunyoung; Aquavella, James V; Zavislan, James; Hindman, Holly B

2016-01-01

To compare the temperatures of the ocular surface, eyelid, and periorbital skin in normal eyes with Sjögren's syndrome (SS) eyes, evaporative dry eyes (EDE), and aqueous deficient dry eyes (ADDE). 10 eyes were analyzed in each age-matched group (normal, SS, EDE, and ADDE). A noninvasive infrared thermal camera captured two-dimensional images in three regions of interest (ROI) in each of three areas: the ocular surface, the upper eyelid, and the periorbital skin within a controlled environmental chamber. Mean temperatures in each ROI were calculated from the videos. Ocular surface time-segmented cooling rates were calculated over a 5-s blink interval. Relative to normal eyes, dry eyes had lower initial central OSTs (SS -0.71°C, EDE -0.55°C, ADDE -0.95°C, KW P<.0001) and lower central upper lid temperatures (SS -0.24°C, ADDE -0.51°C, and EDE -0.54°C, KW P<.0001). ADDE eyes had the lowest initial central OST (P<.0001), while EDE eyes had the lowest central lid temperature and lower periorbital temperatures (P<.0001). Over the 5-s interblink interval, the greatest rate of temperature loss occurred following eyelid opening, but varied by group (normals -0.52, SS -0.73, EDE -0.63, and ADDE -0.75°C/s). The ADDE group also had the most substantial heat loss over the 5-s interblink interval (-0.97°C). Differences in OST may be related to thermal differences in lids and periorbita along with an altered tear film. Thermography of the ocular surface, lids, and surrounding tissues may help to differentiate between different etiologies of dry eye. Copyright © 2016 Elsevier Inc. All rights reserved.

The effect of the corneal epithelium on the intraocular penetration of fluoroquinolone ophthalmic solution.

PubMed

Fukuda, Masamichi; Inoue, Amane; Sasaki, Kazuyuki; Takahashi, Nobuo

2004-01-01

Pharmacokinetic studies of antibacterial agents for infectious eye diseases have usually been performed on normal rabbit eyes. In this study, the intraocular penetration of fluoroquinolone ophthalmic solutions was determined in normal rabbit eyes and in rabbit eyes that had the corneal epithelium intentionally removed. We determined the intraocular penetration of ofloxacin (OFLX), levofloxacin (LVFX), and norfloxacin (NFLX), fluoroquinolone ophthalmic solutions that are already on the market and undergoing clinical studies, by injecting 50 microl of each solution into the cul-de-sacs of rabbit eyes three times at 15-min intervals. The drug concentration at 10, 30, 60, 120, and 240 min after final instillation was determined by high-performance liquid chromatography. The maximum concentration in the aqueous humor of normal rabbit eyes was 2.09 +/- 1.56 microg/ml (60 min, OFLX), 2.57 +/- 1.00 microg/ml (30 min, LVFX), and 0.42 +/- 0.12 microg/ml (120 min, NFLX). The drug concentration in the aqueous humor of eyes with intentionally removed corneal epithelium was 12.50 +/- 5.62 microg/ml (30 min, OFLX), 9.02 +/- 2.45 microg/ml (60 min, LVFX), and 8.54 +/- 5.17 microg/ml (30 min, NFLX). The drug penetration of the eye drops into eyes with removed corneal epithelium was around 6 times (OFLX), 3.5 times (LVFX), and 20 times (NFLX) higher than the penetration into the eye with normal cornea. Among the pharmacokinetic parameters of the three ophthalmic solutions according to the one-compartment model, the maximum concentration in the aqueous and the area under the concentration-time curve in the aqueous tended to be higher in the eyes with intentionally removed corneal epithelia than in those with normal corneas.

Comparison of noncontact infrared and remote sensor thermometry in normal and dry eye patients.

PubMed

Singh, G; Singh Bhinder, H

To evaluate the role of closed chamber infrared and remote sensor thermometry in normal and dry eye patients. The study was conducted on 51 dry eye cases (102 eyes), 26 men and 25 women aged 19 to 65 years (35.3614.36), and 51 normal (102 eyes) age- and sex-matched control subjects. The criteria for dry eye were Schirm e r-1 (<10 m/5 min), FTBUT (<10 sec), nd lissamine green score (>2). The remote sensor and infrared thermometry was done in losed chamber around the eye in closed and open eye positions. In normal eyes, closed chamber infrared thermometry recorded temperature 34.770.37 C in closed eye position and 35.020.39 C in open eye position as compared to 27.912.46 C in closed eye position and 28.012.46 C in open position with remote sensor thermometry. The difference in temperature from closed to open position was 0.250.90 C in infrared thermometry and 0.100.00 C with remote sensor thermometry, which was statistically significant (p<0.0000). In dry eye, the infrared therm o m e t ry recorded 35.080.61 C temperature in closed eye position and 35.530.63 C in open eye position as compared to 27.412.48 C in open and closed eye position with remote sensor thermometry. The difference in temperature from closed to open eye position was 0.450.14 C (p<0.0000) with infrared thermometry as compared to no change 0.000.00 C with remote sensor thermometry (p<0.0000). Remote sensor thermometry proved better for diagnosis of dry eye disease as it showed no change in temperature under closed chamber in closed and open position (p=0.0000). Infrared thermometry was better in recording the absolute temperature from any point on the eye.

Comparison of noncontact infrared and remote sensor thermometry in normal and dry eye patients.

PubMed

Singh, G; Bhinder, H Singh

2005-01-01

To evaluate the role of closed chamber infrared and remote sensor thermometry in normal and dry eye patients. The study was conducted on 51 dry eye cases (102 eyes), 26 men and 25 women aged 19 to 65 years (35.36+/-14.36), and 51 normal (102 eyes) age- and sex-matched control subjects. The criteria for dry eye were Schirmer-1 (<10 m/5 min), FTBUT (<10 sec), nd lissamine green score (>2). The remote sensor and infrared thermometry was done in closed chamber around the eye in closed and open eye positions. In normal eyes, closed chamber infrared thermometry recorded temperature 34.77+/-0.37 degrees C in closed eye position and 35.02+/-0.39 degrees C in open eye position as compared to 27.91+/-2.46 degrees C in closed eye position and 28.01+/-2.46 degrees C in open position with remote sensor thermometry. The difference in temperature from closed to open position was 0.25+/-0.90 degrees C in infrared thermometry and 0.10+/-0.00 degrees C with remote sensor thermometry, which was statistically significant (p<0.0000). In dry eye, the infrared thermometry recorded 35.08+/-0.61 degrees C temperature in closed eye position and 35.53+/-0.63 degrees C in open eye position as compared to 27.41+/-2.48 degrees C in open and closed eye position with remote sensor thermometry. The difference in temperature from closed to open eye position was 0.45+/-0.14 degrees C (p<0.0000) with infrared thermometry as compared to no change 0.00+/-0.00 degrees C with remote sensor thermometry (p<0.0000). Remote sensor thermometry proved better for diagnosis of dry eye disease as it showed no change in temperature under closed chamber in closed and open position (p=0.0000). Infrared thermometry was better in recording the absolute temperature from any point on the eye.

Whole eye wavefront aberrations in Mexican male subjects.

PubMed

Cantú, Roberto; Rosales, Marco A; Tepichín, Eduardo; Curioca, Andrée; Montes, Victor; Bonilla, Julio

2004-01-01

To analyze the characteristics, incidence, and appearance of wavefront aberrations in undilated, normal, unoperated eyes. Eighty-eight eyes of 44 healthy male Mexican subjects (mean age 25.32 years, range 18 to 36 yr) were divided into three groups based on uncorrected visual acuity of greater than or equal to 20/20, 20/30, or 20/40. UCVA measurements were obtained using an Acuity Max computer screen chart. Wavefront aberrations were measured with the Nidek OPD-Scan ARK 10000, Ver. 1.11b. All measurements were carried out at the same center by the same technician during a single session, following manufacturer instructions. Background illumination was 3 Lux. Wavefront aberration measurements for each group were statistically analyzed using StatView; an average eye was characterized and the resulting aberrations were simulated using MATLAB. We obtained wavefront aberration maps for the 20/20 undilated normal unoperated eyes for total, low, and high order aberration coefficients. Wavefront maps for right eyes were practically the same as those for left eyes. Higher aberrations did not contribute substantially to total wavefront analysis. Average aberrations of this "normal eye" will be used as criteria to decide the necessity of wavefront-guided ablation in our facilities. We will focus on the nearly zero average of high order aberrations in this normal whole eye as a reference to be matched.

Syngeneic Schwann cell transplantation preserves vision in RCS rat without immunosuppression.

PubMed

McGill, Trevor J; Lund, Raymond D; Douglas, Robert M; Wang, Shaomei; Lu, Bin; Silver, Byron D; Secretan, Matt R; Arthur, Jennifer N; Prusky, Glen T

2007-04-01

To evaluate the efficacy of immunologically compatible Schwann cells transplanted without immunosuppression in the RCS rat retina to preserve vision. Syngeneic (dystrophic RCS) Schwann cells harvested from sciatic nerves were cultured and transplanted into one eye of dystrophic RCS rats at an early stage of retinal degeneration. Allogeneic (Long-Evans) Schwann cells and unoperated eyes served as controls. Vision through transplanted and unoperated eyes was then quantified using two visual behavior tasks, one measuring the spatial frequency and contrast sensitivity thresholds of the optokinetic response (OKR) and the other measuring grating acuity in a perception task. Spatial frequency thresholds measured through syngeneically transplanted eyes maintained near normal spatial frequency sensitivity for approximately 30 weeks, whereas thresholds through control eyes deteriorated to less than 20% of normal over the same period. Contrast sensitivity was preserved through syngeneically transplanted eyes better than through allogeneic and unoperated eyes, at all spatial frequencies. Grating acuity measured through syngeneically transplanted eyes was maintained at approximately 60% of normal, whereas acuity of allogeneically transplanted eyes was significantly lower at approximately 40% of normal. The ability of immunoprivileged Schwann cell transplants to preserve vision in RCS rats indicates that transplantation of syngeneic Schwann cells holds promise as a preventive treatment for retinal degenerative disease.

Corneal polarimetry after LASIK refractive surgery

NASA Astrophysics Data System (ADS)

Bueno, Juan M.; Berrio, Esther; Artal, Pablo

2006-01-01

Imaging polarimetry provides spatially resolved information on the polarization properties of a system. In the case of the living human eye, polarization could be related to the corneal biomechanical properties, which vary from the normal state as a result of surgery or pathologies. We have used an aberro-polariscope, which we recently developed, to determine and to compare the spatially resolved maps of polarization parameters across the pupil between normal healthy and post-LASIK eyes. The depolarization distribution is not uniform across the pupil, with post-surgery eyes presenting larger levels of depolarization. While retardation increases along the radius in normal eyes, this pattern becomes irregular after LASIK refractive surgery. The maps of slow axis also differ in normal and post-surgery eyes, with a larger disorder in post-LASIK eyes. Since these changes in polarization indicate subtle structural modifications of the cornea, this approach can be useful in a clinical environment to follow the biomechanical and optical changes of the cornea after refractive surgery or for the early diagnosis of different corneal pathologies.

Electroretinography is a prognostic indicator for postoperative vision in dogs undergoing retinal reattachment surgery.

PubMed

Hoffman, Allison; Sisler, Steve; Pappania, Marie; Hsu, Kimberly; Ross, Maya; Ofri, Ron

2018-05-01

To determine whether pre-operative electroretinography (ERG) predicts postoperative vision in dogs undergoing retinal reattachment surgery (RRS). This 18-month prospective study recorded signalment, duration, cause, and extent of retinal detachment and pre-operative vision status. Rod and mixed rod-cone ERG responses were recorded prior to RRS. Referring veterinary ophthalmologists assessed vision 2 months postoperatively. Thirty dogs (40 affected eyes) aged 4 months to 12.1 years were included. The detachment extent was 150 ° -320 ° in 15 of 40 eyes, 360 ° in 24 of 40 eyes, and not recorded in one eye. Most dogs had a genetic predisposition for retinal detachment. Eight eyes of seven dogs had previous cataract surgery. Mean estimated duration of detachment prior to surgery was 24.5 ± 19.6 days. Pre-operatively, 34 of 40 eyes were blind, two of 40 eyes were sighted, and four of 40 eyes had severely diminished vision. Compared to normative ERG values in our clinics, pre-operative ERGs were classified as "normal" in five of 40 eyes, "attenuated" in seven of 40 eyes, and "flat" in 28 of 40 eyes. Following RRS, the retina was fully reattached in all operated eyes. Two-month postoperatively, 30 of 40 eyes had "normal" vision as defined by referring veterinary ophthalmologists, six of 40 eyes had "limited" or "diminished" vision and four of 40 eyes were blind. Normal vision was regained in 12 of 12 (100%) of eyes with normal or attenuated pre-operative ERG's, but only in 18 of 28 (64%) of eyes with flat pre-operative ERG 's (Linear-by-linear test, P = 0.029). A recordable pre-operative ERG, even if attenuated, is associated with return of vision in canine RRS patients, and is a favorable prognostic indicator. © 2017 American College of Veterinary Ophthalmologists.

The relationship between corneal biomechanical properties and confocal microscopy findings in normal and keratoconic eyes.

PubMed

Hurmeric, Volkan; Sahin, Afsun; Ozge, Gokhan; Bayer, Atilla

2010-06-01

To investigate the relationship between corneal biomechanical properties and confocal microscopy (CM) findings in normal and keratoconic eyes. The study consisted of 28 eyes of 28 healthy volunteers and 23 eyes of 15 patients with keratoconus. The diagnosis of keratoconus was made with corneal topography and clinical findings. The corneal hysteresis (CH) and corneal resistance factor (CRF) were measured by the ocular response analyzer. In vivo CM was performed with NIDEK Confoscan 3. CH and CRF were compared with corneal morphological findings (detailed cell counts of endothelial, stromal, and epithelial cells) in vivo. CH was 10.1 +/- 1.3 mm Hg in normal eyes and 7.4 +/- 1.5 mm Hg in keratoconic eyes (P < 0.0001). CRF was 10.1 +/- 1.8 mm Hg in normal eyes and 6.2 +/- 1.4 mm Hg in keratoconic eyes (P < 0.0001). CH and CRF were negatively correlated with full-thickness stromal keratocyte density (P < 0.01; r = -0.52 and P < 0.001; r = -0.67, respectively) in healthy eyes. Keratocyte density of the posterior half of the stroma was found to be significantly related with CRF in healthy eyes (beta = -0.404; P = 0.01). There was no significant relationship among CH, CRF, and CM findings in eyes with keratoconus. There is a significant relationship between CRF and keratocyte density of the posterior half of the stroma in healthy eyes. Our results suggest that corneal elasticity is related to not only stromal matrix but also cellular structure of the cornea.

[The eye, the optic system and its anomalies].

PubMed

Cohen, S Y

1993-09-15

The eye is a perceptive system with extremely complex physiology, although its optical properties can be assimilated to those of spherical diopters. Various approximations make it possible to reduce the eyeball to a single convex diopter. With a normal eye the image of an object situated ad infinitum focuses on the retina. The normal eye is called emmetropic. Otherwise, the eye is called ametropic. Several types of ametropy exist. When the image focuses in front of the retina the eye is said to be myopic. When the image focuses behind the retina the eye is called hypermetropic (or hyperopic). When the image of an object differs according to various focusing axes, the eye is said to be astigmatic.

[Differentially expressed genes of cell signal transduction associated with benzene poisoning by cDNA microarray].

PubMed

Wang, Hong; Bi, Yongyi; Tao, Ning; Wang, Chunhong

2005-08-01

To detect the differential expression of cell signal transduction genes associated with benzene poisoning, and to explore the pathogenic mechanisms of blood system damage induced by benzene. Peripheral white blood cell gene expression profile of 7 benzene poisoning patients, including one aplastic anemia, was determined by cDNA microarray. Seven chips from normal workers were served as controls. Cluster analysis of gene expression profile was performed. Among the 4265 target genes, 176 genes associated with cell signal transduction were differentially expressed. 35 up-regulated genes including PTPRC, STAT4, IFITM1 etc were found in at least 6 pieces of microarray; 45 down-regulated genes including ARHB, PPP3CB, CDC37 etc were found in at least 5 pieces of microarray. cDNA microarray technology is an effective technique for screening the differentially expressed genes of cell signal transduction. Disorder in cell signal transduction may play certain role in the pathogenic mechanism of benzene poisoning.

Cytokine-related genes and oxidation-related genes detected in preeclamptic placentas.

PubMed

Lee, Gui Se Ra; Joe, Yoon Seong; Kim, Sa Jin; Shin, Jong Chul

2010-10-01

To investigate cytokine- and oxidation-related genes for preeclampsia using DNA microarray analysis. Placentas were collected from 13 normal pregnancies and 13 patients with preeclampsia. Gene expression was studied using DNA microarray. Among significantly expressed genes, we focused on genes associated with cytokines and oxidation, and the results were confirmed using quantitative real time-polymerase chain reaction (QRT-PCR). 415 genes out of 30,940 genes were altered by > or =2-fold in the microarray analysis. 121 up-regulated genes and 294 down-regulated genes were found to be in preeclamptic placenta. Six cytokine-related genes and 5 oxidation-related genes were found from among the 121 up-regulated genes. The cytokine-related genes studied included oncostatin M (OSM), fms-related tyrosine kinase (FLT1) and vascular endothelial growth factor A (VEGFA), and the oxidation-related genes studied included spermine oxidase (SMOX), l cytochrome P450, family 26, subfamily A, polypeptide 1 (CYP26A1), acetate dehydrogenase A (LDHA). These six genes were also significantly higher in placentas from patients with preeclampsia than in those from women with normal pregnancies. The placental tissue of patients with preeclampsia showed significantly higher mRNA expression of these six genes than the normal group, using QRT-PCR. DNA microarray analysis is one of the great methods for simultaneously detecting the functionally associated genes of preeclampsia. The cytokine-related genes such as OSM, FLT1 and VEGFA, and the oxidation-related genes such as LDHA, CYP26A1 and SMOX might prove to be the starting point in the elucidation of the pathogenesis of preeclampsia.

High-resolution imaging of retinal nerve fiber bundles in glaucoma using adaptive optics scanning laser ophthalmoscopy.

PubMed

Takayama, Kohei; Ooto, Sotaro; Hangai, Masanori; Ueda-Arakawa, Naoko; Yoshida, Sachiko; Akagi, Tadamichi; Ikeda, Hanako Ohashi; Nonaka, Atsushi; Hanebuchi, Masaaki; Inoue, Takashi; Yoshimura, Nagahisa

2013-05-01

To detect pathologic changes in retinal nerve fiber bundles in glaucomatous eyes seen on images obtained by adaptive optics (AO) scanning laser ophthalmoscopy (AO SLO). Prospective cross-sectional study. Twenty-eight eyes of 28 patients with open-angle glaucoma and 21 normal eyes of 21 volunteer subjects underwent a full ophthalmologic examination, visual field testing using a Humphrey Field Analyzer, fundus photography, red-free SLO imaging, spectral-domain optical coherence tomography, and imaging with an original prototype AO SLO system. The AO SLO images showed many hyperreflective bundles suggesting nerve fiber bundles. In glaucomatous eyes, the nerve fiber bundles were narrower than in normal eyes, and the nerve fiber layer thickness was correlated with the nerve fiber bundle widths on AO SLO (P < .001). In the nerve fiber layer defect area on fundus photography, the nerve fiber bundles on AO SLO were narrower compared with those in normal eyes (P < .001). At 60 degrees on the inferior temporal side of the optic disc, the nerve fiber bundle width was significantly lower, even in areas without nerve fiber layer defect, in eyes with glaucomatous eyes compared with normal eyes (P = .026). The mean deviations of each cluster in visual field testing were correlated with the corresponding nerve fiber bundle widths (P = .017). AO SLO images showed reduced nerve fiber bundle widths both in clinically normal and abnormal areas of glaucomatous eyes, and these abnormalities were associated with visual field defects, suggesting that AO SLO may be useful for detecting early nerve fiber bundle abnormalities associated with loss of visual function. Copyright © 2013 Elsevier Inc. All rights reserved.

Physiologic Inter-eye Differences in Monkey Optic Nerve Head Architecture and Their Relation to Changes in Early Experimental Glaucoma

PubMed Central

Yang, Hongli; Downs, J. Crawford; Burgoyne, Claude F.

2009-01-01

Purpose To characterize physiologic inter-eye differences in optic nerve head (ONH) architecture within six normal rhesus monkeys and compare them to inter-eye differences within three previously-reported cynomolgus monkeys with early experimental glaucoma (EEG). Methods Trephinated ONH and peripapillary sclera from both eyes of six normal monkeys were serial sectioned, 3D reconstructed, 3D delineated and parameterized. For each normal animal, and each parameter, physiologic inter-eye difference (PID) was calculated (both overall and regionally) by converting all OS data to OD configuration and subtracting the OS from the OD value and Physiologic Inter-eye Percent Difference (PIPD) was calculated as the PID divided by the measurement mean of the two eyes. For each EEG monkey, inter-eye (EEG minus normal) differences and percent differences for each parameter overall and regionally were compared to the PID and PIPD Maximums. Results For all parameters the PID Maximums were relatively small overall. Compared to overall PID maximums, overall inter-eye differences in EEG monkeys were greatest for laminar deformation and thickening, posterior scleral canal enlargement, cupping and prelaminar neural tissue thickening. Compared to the regional PID Maximums, the lamina cribrosa was posteriorly deformed centrally, inferiorly, inferonasally and superiorly and was thickened centrally. The prelaminar neural tissues were thickened inferiorly, inferonasally and superiorly. Conclusion These data provide the first characterization of PID/PIPD maximums for ONH neural and connective tissue parameters in normal monkeys and serve to further clarify the location and character of early ONH change in experimental glaucoma. However, because of the species differences, the findings in EEG need to be confirmed within EEG rhesus monkey eyes. PMID:18775866

The Effect of Ocular Surface Regularity on Contrast Sensitivity and Straylight in Dry Eye.

PubMed

Koh, Shizuka; Maeda, Naoyuki; Ikeda, Chikako; Asonuma, Sanae; Ogawa, Mai; Hiraoka, Takahiro; Oshika, Tetsuro; Nishida, Kohji

2017-05-01

To investigate the association between visual function and ocular surface regularity in dry eye. We enrolled 52 eyes of 52 dry eye patients (34 dry eyes with superficial punctate keratopathy [SPK] in the central corneal region [central SPK] and 18 dry eyes without central SPK) and 20 eyes of 20 normal control subjects. All eyes had a best-corrected distance visual acuity better than 20/20. We measured two indices of contrast sensitivity function under photopic conditions: contrast sensitivity and letter contrast sensitivity. The area under the log contrast sensitivity function (AULCSF) was calculated from the obtained contrast sensitivity data. Straylight was quantified using a straylight meter. Dry eyes with central SPK had significantly decreased contrast sensitivity function, including AULCSF and letter contrast sensitivity than those without central SPK and normal eyes (P < 0.05 for each). While the straylight values in both dry eye groups did not differ, straylight values were greater than those in normal eyes (P < 0.05 for both). In dry eye, the AULCSF and letter contrast sensitivity negatively correlated with the central SPK score (R = -0.485, P < 0.001, and R = -0.541, P < 0.001, respectively). In dry eye, reduced contrast sensitivity in part results from central SPK overlying the optical zone and the increased straylight results from tear film instability rather than central SPK.

Identification of differentially expressed genes and false discovery rate in microarray studies.

PubMed

Gusnanto, Arief; Calza, Stefano; Pawitan, Yudi

2007-04-01

To highlight the development in microarray data analysis for the identification of differentially expressed genes, particularly via control of false discovery rate. The emergence of high-throughput technology such as microarrays raises two fundamental statistical issues: multiplicity and sensitivity. We focus on the biological problem of identifying differentially expressed genes. First, multiplicity arises due to testing tens of thousands of hypotheses, rendering the standard P value meaningless. Second, known optimal single-test procedures such as the t-test perform poorly in the context of highly multiple tests. The standard approach of dealing with multiplicity is too conservative in the microarray context. The false discovery rate concept is fast becoming the key statistical assessment tool replacing the P value. We review the false discovery rate approach and argue that it is more sensible for microarray data. We also discuss some methods to take into account additional information from the microarrays to improve the false discovery rate. There is growing consensus on how to analyse microarray data using the false discovery rate framework in place of the classical P value. Further research is needed on the preprocessing of the raw data, such as the normalization step and filtering, and on finding the most sensitive test procedure.

A microarray analysis of retinal transcripts that are controlled by image contrast in mice.

PubMed

Brand, Christine; Schaeffel, Frank; Feldkaemper, Marita Pauline

2007-06-18

The development of myopia is controlled by still largely unknown retinal signals. The aim of this study was to investigate the changes in retinal mRNA expression after different periods of visual deprivation in mice, while controlling for retinal illuminance. Each group consisted of three male C57BL/6 mice. Treatment periods were 30 min, 4 h, and 6+6 h. High spatial frequencies were filtered from the retinal image by frosted diffusers over one eye while the fellow eyes were covered by clear neutral density (ND) filters that exhibited similar light attenuating properties (0.1 log units) as the diffusers. For the final 30 min of the respective treatment period mice were individually placed in a clear Perspex cylinder that was positioned in the center of a rotating (60 degrees) large drum. The inside of the drum was covered with a 0.1 cyc/degree vertical square wave grating. This visual environment was chosen to standardize illuminances and contrasts seen by the mice. Labeled cRNA was prepared and hybridized to Affymetrix GeneChip Mouse Genome 430 2.0 arrays. Alterations in mRNA expression levels of candidate genes with potential biological relevance were confirmed by semi-quantitative real-time reverse transcription polymerase chain reaction (RT-PCR). In all groups, Egr-1 mRNA expression was reduced in diffuser-treated eyes. Furthermore, the degradation of the spatial frequency spectrum also changed the cFos mRNA level, with reduced expression after 4 h of diffuser treatment. Other interesting candidates were Akt2, which was up-regulated after 30 min of deprivation and Mapk8ip3, a neuron specific JNK binding and scaffolding protein that was temporally regulated in the diffuser-treated eyes only. The microarray analysis demonstrated a pattern of differential transcriptional changes, even though differences in the retinal images were restricted to spatial features. The candidate genes may provide further insight into the biochemical short-term changes following retinal image degradation in mice. Because deprivation of spatial vision leads to increased eye growth and myopia in both animals and humans, it is believed some of the identified genes play a role in myopia development.

Systematic gene microarray analysis of the lncRNA expression profiles in human uterine cervix carcinoma.

PubMed

Chen, Jie; Fu, Ziyi; Ji, Chenbo; Gu, Pingqing; Xu, Pengfei; Yu, Ningzhu; Kan, Yansheng; Wu, Xiaowei; Shen, Rong; Shen, Yan

2015-05-01

The human uterine cervix carcinoma is one of the most well-known malignancy reproductive system cancers, which threatens women health globally. However, the mechanisms of the oncogenesis and development process of cervix carcinoma are not yet fully understood. Long non-coding RNAs (lncRNAs) have been proved to play key roles in various biological processes, especially development of cancer. The function and mechanism of lncRNAs on cervix carcinoma is still rarely reported. We selected 3 cervix cancer and normal cervix tissues separately, then performed lncRNA microarray to detect the differentially expressed lncRNAs. Subsequently, we explored the potential function of these dysregulated lncRNAs through online bioinformatics databases. Finally, quantity real-time PCR was carried out to confirm the expression levels of these dysregulated lncRNAs in cervix cancer and normal tissues. We uncovered the profiles of differentially expressed lncRNAs between normal and cervix carcinoma tissues by using the microarray techniques, and found 1622 upregulated and 3026 downregulated lncRNAs (fold-change>2.0) in cervix carcinoma compared to the normal cervical tissue. Furthermore, we found HOXA11-AS might participate in cervix carcinogenesis by regulating HOXA11, which is involved in regulating biological processes of cervix cancer. This study afforded expression profiles of lncRNAs between cervix carcinoma tissue and normal cervical tissue, which could provide database for further research about the function and mechanism of key-lncRNAs in cervix carcinoma, and might be helpful to explore potential diagnosis factors and therapeutic targets for cervix carcinoma. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Contrast masking in strabismic amblyopia: attenuation, noise, interocular suppression and binocular summation.

PubMed

Baker, Daniel H; Meese, Tim S; Hess, Robert F

2008-07-01

To investigate amblyopic contrast vision at threshold and above we performed pedestal-masking (contrast discrimination) experiments with a group of eight strabismic amblyopes using horizontal sinusoidal gratings (mainly 3c/deg) in monocular, binocular and dichoptic configurations balanced across eye (i.e. five conditions). With some exceptions in some observers, the four main results were as follows. (1) For the monocular and dichoptic conditions, sensitivity was less in the amblyopic eye than in the good eye at all mask contrasts. (2) Binocular and monocular dipper functions superimposed in the good eye. (3) Monocular masking functions had a normal dipper shape in the good eye, but facilitation was diminished in the amblyopic eye. (4) A less consistent result was normal facilitation in dichoptic masking when testing the good eye, but a loss of this when testing the amblyopic eye. This pattern of amblyopic results was replicated in a normal observer by placing a neutral density filter in front of one eye. The two-stage model of binocular contrast gain control [Meese, T.S., Georgeson, M.A. & Baker, D.H. (2006). Binocular contrast vision at and above threshold. Journal of Vision 6, 1224-1243.] was 'lesioned' in several ways to assess the form of the amblyopic deficit. The most successful model involves attenuation of signal and an increase in noise in the amblyopic eye, and intact stages of interocular suppression and binocular summation. This implies a behavioural influence from monocular noise in the amblyopic visual system as well as in normal observers with an ND filter over one eye.

Evaluating Glaucomatous Retinal Nerve Fiber Damage by GDx VCC Polarimetry in Taiwan Chinese Population

PubMed Central

Chen, Hsin-Yi; Huang, Mei-Ling; Huang, Wei-Cheng

2010-01-01

Purpose To study the capability of scanning laser polarimetry with variable corneal compensation (GDx VCC) to detect differences in retinal nerve fiber layer thickness between normal and glaucomatous eyes in a Taiwan Chinese population. Methods This study included 44 normal eyes and 107 glaucomatous eyes. The glaucomatous eyes were divided into three subgroups on the basis of its visual field defects (early, moderate, severe). Each subject underwent a GDx-VCC exam and visual field testing. The area under the receiver-operating characteristic curve (AROC) of each relevant parameter was used to differentiate normal from each glaucoma subgroup, respectively. The correlation between visual field index and each parameter was evaluated for the eyes in the glaucoma group. Results For normal vs. early glaucoma, the parameter with the best AROC was Nerve fiber indicator (NFI) (0.942). For normal vs. moderate glaucoma, the parameter showing the best AROC was NFI (0.985). For normal vs. severe glaucoma, the parameter that had the best AROC was NFI (1.000). For early vs. moderate glaucoma, the parameter with the best AROC was NFI (0.732). For moderate vs. severe, the parameter showing the best AROC was temporal-superior-nasal-inferior-temporal average (0.652). For early vs. severe, the parameter with the best AROC was NFI (0.852). Conclusions GDx-VCC-measured parameters may serve as a useful tool to distinguish normal from glaucomatous eyes; in particular, NFI turned out to be the best discriminating parameter.

Normal and keratoconic corneal epithelial thickness mapping using Fourier-domain optical coherence tomography

NASA Astrophysics Data System (ADS)

Li, Yan; Tan, Ou; Huang, David

2011-03-01

The detection of early-stage keratoconus is one of the most important safety issues in screening candidates for corneal refractive surgeries. We propose to use epithelial thickness maps to assist the diagnosis of keratoconus. The corneal epithelial thickness in normal and keratoconic eyes was mapped with optical coherence tomography (OCT). A Fourier-domain OCT system capable of acquiring 26,000 axial-scans per second was used. It has an axial resolution of 5μm in cornea. A pachymetry scan pattern (8 radials, 1024 axial-scans each, 6mm diameter, repeat 3 times) centered at the pupil center was used to image the cornea. The 3 repeated radial scans on each meridian were registered and averaged. Then the anterior corneal, posterior corneal and epithelial boundaries were segmented automatically with a computer algorithm by increased signal intensity at corresponding boundaries. The epithelial thickness map was generated by interpolating epithelial thickness profile calculated from each meridian. Normal and keratoconic eyes (24 eyes each) were scanned 3 times. The central epithelial thickness in normal eyes was thicker than those of keratoconic eyes (mean difference 2.1 μm, t-test p=0.05). The epithelium was thinner superiorly than inferiorly in normal eyes (mean difference -1.4+/-1.1μm, p<0.001) while thicker superiorly than inferiorly in keratoconic eyes (2.0+/-4.1 μm, p=0.02).

Overcoming confounded controls in the analysis of gene expression data from microarray experiments.

PubMed

Bhattacharya, Soumyaroop; Long, Dang; Lyons-Weiler, James

2003-01-01

A potential limitation of data from microarray experiments exists when improper control samples are used. In cancer research, comparisons of tumour expression profiles to those from normal samples is challenging due to tissue heterogeneity (mixed cell populations). A specific example exists in a published colon cancer dataset, in which tissue heterogeneity was reported among the normal samples. In this paper, we show how to overcome or avoid the problem of using normal samples that do not derive from the same tissue of origin as the tumour. We advocate an exploratory unsupervised bootstrap analysis that can reveal unexpected and undesired, but strongly supported, clusters of samples that reflect tissue differences instead of tumour versus normal differences. All of the algorithms used in the analysis, including the maximum difference subset algorithm, unsupervised bootstrap analysis, pooled variance t-test for finding differentially expressed genes and the jackknife to reduce false positives, are incorporated into our online Gene Expression Data Analyzer ( http:// bioinformatics.upmc.edu/GE2/GEDA.html ).

The effect of mitomycin C trabeculectomy on the progression of visual field defect in normal-tension glaucoma.

PubMed

Hagiwara, Y; Yamamoto, T; Kitazawa, Y

2000-03-01

We investigated in a prospective fashion the visual prognosis and complications in normal-tension glaucoma following unilateral trabeculectomy with adjunctive mitomycin C. Trabeculectomy with adjunctive mitomycin C was carried out unilaterally in 21 cases of normal-tension glaucoma. Intraocular pressure (IOP), visual prognosis, and complications were compared between the operated eyes and the non-operated fellow eyes. The follow-up period ranged from 2 to 7 years. The IOP dropped significantly from 14.8+/-1.8 mmHg (mean +/- SD) to 9.6+/-3.9 mmHg in the operated eyes (P=0.0002, Wilcoxon signed-rank test), but did not drop in the non-operated eyes. The mean deviation (MD) was -12.69+/-6.41 dB preoperatively and -14.70+/-5.49 dB at the last clinic visit in the operated eyes, whereas in non-operated eyes it was -7.85+/-5.65 dB and -11.15+/-5.62 dB, respectively. The MD deteriorated significantly in both operated and non-operated eyes (operated eyes P=0.0239, non-operated eyes: P=0.0002; Wilcoxon signed-rank test). The MD slope was -0.37+/-0.60 dB/year and -0.71+/-0.89 dB/year for the operated and non-operated eyes, respectively (P=0.5243, Mann-Whitney U-test). Visual field deterioration was more frequently observed in the non-operated eyes by a pointwise definition of the progression (P<0.05, McNemar test). Visual acuity deteriorated in 6 of the operated eyes and in 5 of the non-operated eyes. Cataract developed in 6 (29%) of the 21 operated eyes, while among the non-operated eyes 4 (19%) developed cataract. Mitomycin C trabeculectomy is effective in delaying progression of visual field defect in normal-tension glaucoma, but complications may arise and cause some visual disturbance.

Enhancing interdisciplinary mathematics and biology education: a microarray data analysis course bridging these disciplines.

PubMed

Tra, Yolande V; Evans, Irene M

2010-01-01

BIO2010 put forth the goal of improving the mathematical educational background of biology students. The analysis and interpretation of microarray high-dimensional data can be very challenging and is best done by a statistician and a biologist working and teaching in a collaborative manner. We set up such a collaboration and designed a course on microarray data analysis. We started using Genome Consortium for Active Teaching (GCAT) materials and Microarray Genome and Clustering Tool software and added R statistical software along with Bioconductor packages. In response to student feedback, one microarray data set was fully analyzed in class, starting from preprocessing to gene discovery to pathway analysis using the latter software. A class project was to conduct a similar analysis where students analyzed their own data or data from a published journal paper. This exercise showed the impact that filtering, preprocessing, and different normalization methods had on gene inclusion in the final data set. We conclude that this course achieved its goals to equip students with skills to analyze data from a microarray experiment. We offer our insight about collaborative teaching as well as how other faculty might design and implement a similar interdisciplinary course.

Enhancing Interdisciplinary Mathematics and Biology Education: A Microarray Data Analysis Course Bridging These Disciplines

PubMed Central

Evans, Irene M.

2010-01-01

BIO2010 put forth the goal of improving the mathematical educational background of biology students. The analysis and interpretation of microarray high-dimensional data can be very challenging and is best done by a statistician and a biologist working and teaching in a collaborative manner. We set up such a collaboration and designed a course on microarray data analysis. We started using Genome Consortium for Active Teaching (GCAT) materials and Microarray Genome and Clustering Tool software and added R statistical software along with Bioconductor packages. In response to student feedback, one microarray data set was fully analyzed in class, starting from preprocessing to gene discovery to pathway analysis using the latter software. A class project was to conduct a similar analysis where students analyzed their own data or data from a published journal paper. This exercise showed the impact that filtering, preprocessing, and different normalization methods had on gene inclusion in the final data set. We conclude that this course achieved its goals to equip students with skills to analyze data from a microarray experiment. We offer our insight about collaborative teaching as well as how other faculty might design and implement a similar interdisciplinary course. PMID:20810954

Comparison of smooth pursuit and combined eye-head tracking in human subjects with deficient labyrinthine function

NASA Technical Reports Server (NTRS)

Leigh, R. J.; Thurston, S. E.; Sharpe, J. A.; Ranalli, P. J.; Hamid, M. A.

1987-01-01

The effects of deficient labyrinthine function on smooth visual tracking with the eyes and head were investigated, using ten patients with bilateral peripheral vestibular disease and ten normal controls. Active, combined eye-head tracking (EHT) was significantly better in patients than smooth pursuit with the eyes alone, whereas normal subjects pursued equally well in both cases. Compensatory eye movements during active head rotation in darkness were always less in patients than in normal subjects. These data were used to examine current hypotheses that postulate central cancellation of the vestibulo-ocular reflex (VOR) during EHT. A model that proposes summation of an integral smooth pursuit command and VOR/compensatory eye movements is consistent with the findings. Observation of passive EHT (visual fixation of a head-fixed target during en bloc rotation) appears to indicate that in this mode parametric gain changes contribute to modulation of the VOR.

[Diagnosis of a case with Williams-Beuren syndrome with nephrocalcinosis using chromosome microarray analysis].

PubMed

Jin, S J; Liu, M; Long, W J; Luo, X P

2016-12-02

Objective: To explore the clinical phenotypes and the genetic cause for a boy with unexplained growth retardation, nephrocalcinosis, auditory anomalies and multi-organ/system developmental disorders. Method: Routine G-banding and chromosome microarray analysis were applied to a child with unexplained growth retardation, nephrocalcinosis, auditory anomalies and multi-organ/system developmental disorders treated in the Department of Pediatrics of Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology in September 2015 and his parents to conduct the chromosomal karyotype analysis and the whole genome scanning. Deleted genes were searched in the Decipher and NCBI databases, and their relationships with the clinical phenotypes were analyzed. Result: A six-month-old boy was refered to us because of unexplained growth retardation and feeding intolerance.The affected child presented with abnormal manifestation such as special face, umbilical hernia, growth retardation, hypothyroidism, congenital heart disease, right ear sensorineural deafness, hypercalcemia and nephrocalcinosis. The child's karyotype was 46, XY, 16qh + , and his parents' karyotypes were normal. Chromosome microarray analysis revealed a 1 436 kb deletion on the 7q11.23(72701098_74136633) region of the child. This region included 23 protein-coding genes, which were reported to be corresponding to Williams-Beuren syndrome and its certain clinical phenotypes. His parents' results of chromosome microarray analysis were normal. Conclusion: A boy with characteristic manifestation of Williams-Beuren syndrome and rare nephrocalcinosis was diagnosed using chromosome microarray analysis. The deletion on the 7q11.23 might be related to the clinical phenotypes of Williams-Beuren syndrome, yet further studies are needed.

Peripapillary Retinal Nerve Fiber Layer Vascular Microcirculation in Eyes With Glaucoma and Single-Hemifield Visual Field Loss.

PubMed

Chen, Chieh-Li; Bojikian, Karine D; Wen, Joanne C; Zhang, Qinqin; Xin, Chen; Mudumbai, Raghu C; Johnstone, Murray A; Chen, Philip P; Wang, Ruikang K

2017-05-01

Understanding the differences in vascular microcirculation of the peripapillary retinal nerve fiber layer (RNFL) between the hemispheres in eyes with glaucoma with single-hemifield visual field (VF) defects may provide insight into the pathophysiology of glaucoma. To investigate the changes in the microcirculation of the peripapillary RNFL of eyes with glaucoma by using optical microangiography. Eyes with glaucoma and single-hemifield VF defect and normal eyes underwent scanning using an optical microangiography system covering a 6.7 × 6.7-mm2 area centered at the optic nerve head. The RNFL microcirculation was measured within an annulus region centered at the optic nerve head divided into superior and inferior hemispheres. Blood flux index (the mean flow signal intensity in the vessels) and vessel area density (the percentage of the detected vessels in the annulus) were measured. Differences in microcirculation between the hemispheres in eyes with glaucoma and normal eyes and correlations among blood flow metrics, VF thresholds, and clinical optical coherence tomography structural measurements were assessed. Twenty-one eyes from 21 patients with glaucoma (7 men and 14 women; mean [SD] age, 63.7 [9.9] years) and 20 eyes from 20 healthy control individuals (9 men and 11 women; mean [SD] age, 68.3 [10.7] years) were studied. In eyes with glaucoma, the abnormal hemisphere showed a thinner RNFL (mean [SE] difference, 23.5 [4.5] μm; 95% CI, 15.1-32.0 µm; P < .001), lower RNFL blood flux index (mean [SE] difference, 0.04 [0.01]; 95% CI, 0.02-0.05; P < .001), and less vessel area density (mean [SE] difference, 0.08% [0.02%]; 95% CI, 0.05%-0.10%; P < .001) than did the normal hemisphere. Compared with normal eyes, reduced RNFL microcirculation was found in the normal hemisphere of eyes with glaucoma, measured by mean [SE] differences in blood flux index (0.06 [0.01]; 95% CI, 0.04-0.09; P < .001) and vessel area density (0.04% [0.02%]; 95% CI, 0.02%-0.08%; P = .003) but not in RNFL thickness (3.4 [4.7] μm; 95% CI, -6.2 to 12.9 µm; P = .48). Strong correlations were found between the blood flux index and VF mean deviation (Spearman ρ = 0.44; P = .045) and RNFL thickness (Spearman ρ = 0.65; P = .001) in the normal hemisphere of the eye with glaucoma. Reduced RNFL microcirculation was detected in the normal hemisphere of eyes with glaucoma, with strong correspondence with VF loss and RNFL thinning. Although the results suggest that vascular dysfunction precedes structural changes seen in glaucoma, longitudinal studies would be needed to confirm this finding.

[The 8-year follow-up study for clinical diagnostic potentials of frequency-doubling technology perimetry for perimetrically normal eyes of open-angle glaucoma patients with unilateral visual field loss].

PubMed

Fan, X; Wu, L L; Xiao, G G; Ma, Z Z; Liu, F

2018-03-11

Objective: To analyze potentials of frequency-doubling technology perimetry (FDP) for diagnosing open-angle glaucoma (OAG) in perimetrically normal eyes of OAG patients diagnosed with standard automated perimetry (SAP) and relating factors from abnormalities on FDP to visual field loss on SAP. Methods: A prospective cohort study. Sixty-eight eyes of 68 OAG patients visiting the ophthalmic clinic of Peking University Third Hospital during November 2003 and October 2007 [32 primary open-angle glaucoma patients and 36 normal tension glaucoma patients, 32 males and 36 females, with an average age of (59±13) years] with unilateral field loss detected by SAP (Octopus101 tG2 program) were examined with the FDP N-30 threshold program (Humphrey Instruments) at baseline. Two groups, FDP positive group and FDP negative group, were divided based on the FDP results, and visual field examinations were followed by a series of SAP examinations for the perimetrically normal eyes over 8 years. During the follow-up, the difference of the converting rate of SAP tests between the two groups was analyzed. Differences between "convertors" and "non-convertors" of SAP tests in the FDP positive group, such as the cup-to-disk ratio and glaucomatous optic neuropathy rate, were also compared with the independent-sample t test or Wilcoxon two-sample test for continuous variable data and the χ(2) test or Fisher exact test for classified variable data and rates. Results: Forty-eight perimetrically normal eyes of 48 participants had complete data and a qualifying follow-up. Baseline FDP results were positive in 33 eyes and negative in 15 eyes. Of the eyes with positive FDP results, 22 eyes developed abnormal SAP results after 4.0 to 90.0 months (median 14.5 months) , whereas none of the eyes with negative FDP results developed abnormal SAP results. For perimetrically normal eyes in the FDP positive group, "converters" showed a greater cup-to-disk ratio (0.73±0.09 vs . 0.63±0.14, Wilcoxon two-sample test, P= 0.011) and more eyes with glaucomatous optic neuropathy (19/22 vs . 4/11, Fisher exact test, P= 0.006). Conclusions: In perimetrically normal eyes of OAG patients, FDP could detect visual field loss of these eyes and predict to some extent future visual field loss on SAP. Severity of glaucomatous optic neuropathy at baseline is related to converting from abnormalities on FDP to visual field loss on SAP. (Chin J Ophthalmol, 2018, 54: 177-183) .

Comparative pharmacokinetics of rhein in normal and loperamide-induced constipated rats and microarray analysis of drug-metabolizing genes.

PubMed

Hou, Mei-Ling; Chang, Li-Wen; Lin, Chi-Hung; Lin, Lie-Chwen; Tsai, Tung-Hu

2014-09-11

Rhein is a pharmacological active component found in Rheum palmatum L. that is the major herb of the San-Huang-Xie-Xin-Tang (SHXXT), a medicinal herbal product used as a remedy for constipation. Here we have investigated the comparative pharmacokinetics of rhein in normal and constipated rats. Microarray analysis was used to explore whether drug-metabolizing genes will be altered after SHXXT treatment. The comparative pharmacokinetics of rhein in normal and loperamide-induced constipated rats was studied by liquid chromatography with electrospray ionization tandem mass spectrometry (LC-MS/MS). Gene expression profiling in drug-metabolizing genes after SHXXT treatment was investigated by microarray analysis and real-time polymerase chain reaction (RT-PCR). A validated LC-MS/MS method was applied to investigate the comparative pharmacokinetics of rhein in normal and loperamide-induced constipated rats. The pharmacokinetic results demonstrate that the loperamide-induced constipation reduced the absorption of rhein. Cmax significantly reduced by 2.5-fold, the AUC decreased by 27.8%; however, the elimination half-life (t1/2) was prolonged by 1.6-fold. Tmax and mean residence time (MRT) were significantly prolonged by 2.8-fold, and 1.7-fold, respectively. The volume of distribution (Vss) increased by 2.2-fold. The data of microarray analysis on gene expression indicate that five drug-metabolizing genes, including Cyp7a1, Cyp2c6, Ces2e, Atp1b1, and Slc7a2 were significantly altered by the SHXXT (0.5 g/kg) treatment. The loperamide-induced constipation reduced the absorption of rhein. Since among the 25,338 genes analyzed, there were five genes significantly altered by SHXXT treatment. Thus, information on minor drug-metabolizing genes altered by SHXXT treatment indicates that SHXXT is relatively safe for clinical application. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Correcting for batch effects in case-control microbiome studies

PubMed Central

Gibbons, Sean M.; Duvallet, Claire

2018-01-01

High-throughput data generation platforms, like mass-spectrometry, microarrays, and second-generation sequencing are susceptible to batch effects due to run-to-run variation in reagents, equipment, protocols, or personnel. Currently, batch correction methods are not commonly applied to microbiome sequencing datasets. In this paper, we compare different batch-correction methods applied to microbiome case-control studies. We introduce a model-free normalization procedure where features (i.e. bacterial taxa) in case samples are converted to percentiles of the equivalent features in control samples within a study prior to pooling data across studies. We look at how this percentile-normalization method compares to traditional meta-analysis methods for combining independent p-values and to limma and ComBat, widely used batch-correction models developed for RNA microarray data. Overall, we show that percentile-normalization is a simple, non-parametric approach for correcting batch effects and improving sensitivity in case-control meta-analyses. PMID:29684016

Identification of Differentially Expressed IGFBP5-Related Genes in Breast Cancer Tumor Tissues Using cDNA Microarray Experiments.

PubMed

Akkiprik, Mustafa; Peker, İrem; Özmen, Tolga; Amuran, Gökçe Güllü; Güllüoğlu, Bahadır M; Kaya, Handan; Özer, Ayşe

2015-11-10

IGFBP5 is an important regulatory protein in breast cancer progression. We tried to identify differentially expressed genes (DEGs) between breast tumor tissues with IGFBP5 overexpression and their adjacent normal tissues. In this study, thirty-eight breast cancer and adjacent normal breast tissue samples were used to determine IGFBP5 expression by qPCR. cDNA microarrays were applied to the highest IGFBP5 overexpressed tumor samples compared to their adjacent normal breast tissue. Microarray analysis revealed that a total of 186 genes were differentially expressed in breast cancer compared with normal breast tissues. Of the 186 genes, 169 genes were downregulated and 17 genes were upregulated in the tumor samples. KEGG pathway analyses showed that protein digestion and absorption, focal adhesion, salivary secretion, drug metabolism-cytochrome P450, and phenylalanine metabolism pathways are involved. Among these DEGs, the prominent top two genes (MMP11 and COL1A1) which potentially correlated with IGFBP5 were selected for validation using real time RT-qPCR. Only COL1A1 expression showed a consistent upregulation with IGFBP5 expression and COL1A1 and MMP11 were significantly positively correlated. We concluded that the discovery of coordinately expressed genes related with IGFBP5 might contribute to understanding of the molecular mechanism of the function of IGFBP5 in breast cancer. Further functional studies on DEGs and association with IGFBP5 may identify novel biomarkers for clinical applications in breast cancer.

A Versatile Microarray Platform for Capturing Rare Cells

NASA Astrophysics Data System (ADS)

Brinkmann, Falko; Hirtz, Michael; Haller, Anna; Gorges, Tobias M.; Vellekoop, Michael J.; Riethdorf, Sabine; Müller, Volkmar; Pantel, Klaus; Fuchs, Harald

2015-10-01

Analyses of rare events occurring at extremely low frequencies in body fluids are still challenging. We established a versatile microarray-based platform able to capture single target cells from large background populations. As use case we chose the challenging application of detecting circulating tumor cells (CTCs) - about one cell in a billion normal blood cells. After incubation with an antibody cocktail, targeted cells are extracted on a microarray in a microfluidic chip. The accessibility of our platform allows for subsequent recovery of targets for further analysis. The microarray facilitates exclusion of false positive capture events by co-localization allowing for detection without fluorescent labelling. Analyzing blood samples from cancer patients with our platform reached and partly outreached gold standard performance, demonstrating feasibility for clinical application. Clinical researchers free choice of antibody cocktail without need for altered chip manufacturing or incubation protocol, allows virtual arbitrary targeting of capture species and therefore wide spread applications in biomedical sciences.

Do Unilateral Herpetic Stromal Keratitis and Neurotrophic Ulcers Cause Bilateral Dry Eye?

PubMed

Jabbarvand, Mahmoud; Hashemian, Hesam; Khodaparast, Mehdi; Rafatnejad, Amin; Beheshtnejad, Amirhooshang; Salami, Amir

2015-07-01

To evaluate and compare the ocular surface condition in herpetic interstitial stromal keratitis and neurotrophic ulcer groups and their normal fellow eyes. In this observational, cross-sectional case-control study, 85 consecutive patients were included, including 56 cases of treated herpetic interstitial keratitis and 29 patients with neurotrophic ulcers. Fifty-six age- and sex-matched participants were also recruited from a normal population as the control group. We evaluated and scored the subjective and objective measures of dry eye for both eyes of all patients. Then, we compared the score of the groups with one another and also with the control group. The main outcome measures were the discomfort level, visual symptoms of dry eye, conjunctival injection, conjunctival staining, corneal staining, corneal tear signs of dry eye, meibomian gland dysfunction, tear break-up time, Schirmer test score with anesthesia, and tear osmolarity. The normal fellow eye of the herpetic keratitis group had significantly higher discomfort levels (1.4 ± 0.9 vs. 1.3 ± 0.5, P = 0.003), visual symptoms (1.7 ± 0.8 vs. 1.3 ± 0.7, P = 0.002), tear break-up time (8.3 ± 3.2 vs. 12.1 ± 3.3 seconds, P = 0.003), Schirmer test scores (9.2 ± 3.9 vs. 12.9 ± 3 mm, P = 0.04), and tear osmolarity (9.2 ± 3.9 vs. 12.9 ± 3 mm, P = 0.003) in comparison with normal controls. The normal fellow eyes of the neurotrophic ulcer group had significantly worse values for discomfort level (1.9 ± 0.9 vs. 1.3 ± 0.5, P < 0.001), tear break-up time (7.9 ± 4 vs. 12.1 ± 3.3, P = 0.004), Schirmer test score (8.1 ± 3.9 vs. 12.9 ± 3, P = 0.005), and tear osmolarity (295 ± 9.2 vs. 292.7 ± 5.9, P = 0.02) compared with normal controls. Both eyes of patients with neurotrophic ulcer and interstitial herpetic keratitis have a significantly poorer ocular surface condition compared with that of normal controls.

Non-Orthogonal Corneal Astigmatism among Normal and Keratoconic Brazilian and Chinese populations.

PubMed

Abass, Ahmed; Clamp, John; Bao, FangJun; Ambrósio, Renato; Elsheikh, Ahmed

2018-06-01

To investigate the prevalence of non-orthogonal astigmatism among normal and keratoconic Brazilian and Chinese populations. Topography data were obtained using the Pentacam High Resolution (HR) system ® from 458 Brazilian (aged 35.6 ± 15.8 years) and 505 Chinese (aged 31.6 ± 10.8 years) eyes with no history of keratoconus or refractive surgery, and 314 Brazilian (aged 24.2 ± 5.7 years) and 74 Chinese (aged 22.0 ± 5.5 years) keratoconic eyes. Orthogonal values of optical flat and steep powers were determined by finding the angular positions of two perpendicular meridians that gave the maximum difference in power. Additionally, the angular positions of the meridians with the minimum and maximum optical powers were located while being unrestricted by the usual orthogonality assumption. Eyes were determined to have non-orthogonal astigmatism if the angle between the two meridians with maximum and minimum optical power deviated by more than 5° from 90°. Evidence of non-orthogonal astigmatism was found in 39% of the Brazilian keratoconic eyes, 26% of the Chinese keratoconic eyes, 29% of the Brazilian normal eyes and 20% of the Chinese normal eyes. The large percentage of participants with non-orthogonal astigmatism in both normal and keratoconic eyes illustrates the need for the common orthogonality assumption to be reviewed when correcting for astigmatism. The prevalence of non-orthogonality should be considered by expanding the prescription system to consider the two power meridians and their independent positions.

Retinal cell imaging in myopic chickens using adaptive optics multiphoton microscopy.

PubMed

Bueno, Juan M; Palacios, Raquel; Giakoumaki, Anastasia; Gualda, Emilio J; Schaeffel, Frank; Artal, Pablo

2014-03-01

Abnormal eye growth induced by visual deprivation can modify the structure and density of the retinal cells. We have used an adaptive optics multiphoton microscope to image photoreceptors (PRs) and ganglion cells (GCs) at different retinal locations in unstained retinas of chicken eyes with about 10D of myopia and their normal-sighted fellow eyes. In all samples, the local averaged inter-PR distance increased with eccentricity. No significant differences in PR density were found between control and myopic eyes. GC density declined in myopic eyes compared to control eyes and the inter-cell distance increased. In normal eyes, the size of the GC cell bodies increased approximately two-fold between the area centralis and the peripheral retina. In myopic eyes, this trend was preserved but the GC bodies were larger at each retinal location, compared to control eyes. Obviously, GC morphology is changing when the retinal area is enlarged in myopic eyes.

Retinal cell imaging in myopic chickens using adaptive optics multiphoton microscopy

PubMed Central

Bueno, Juan M.; Palacios, Raquel; Giakoumaki, Anastasia; Gualda, Emilio J.; Schaeffel, Frank; Artal, Pablo

2014-01-01

Abnormal eye growth induced by visual deprivation can modify the structure and density of the retinal cells. We have used an adaptive optics multiphoton microscope to image photoreceptors (PRs) and ganglion cells (GCs) at different retinal locations in unstained retinas of chicken eyes with about 10D of myopia and their normal-sighted fellow eyes. In all samples, the local averaged inter-PR distance increased with eccentricity. No significant differences in PR density were found between control and myopic eyes. GC density declined in myopic eyes compared to control eyes and the inter-cell distance increased. In normal eyes, the size of the GC cell bodies increased approximately two-fold between the area centralis and the peripheral retina. In myopic eyes, this trend was preserved but the GC bodies were larger at each retinal location, compared to control eyes. Obviously, GC morphology is changing when the retinal area is enlarged in myopic eyes. PMID:24688804

Don't it make my blue eyes brown: heterochromia and other abnormalities of the iris

PubMed Central

Rennie, I G

2012-01-01

Eye colour is one of the most important characteristics in determining facial appearance. In this paper I shall discuss the anatomy and genetics of normal eye colour, together with a wide and diverse range of conditions that may produce an alteration in normal iris pigmentation or form. PMID:21979861

Variable corneal compensation improves discrimination between normal and glaucomatous eyes with the scanning laser polarimeter.

PubMed

Tannenbaum, Dana P; Hoffman, Douglas; Lemij, Hans G; Garway-Heath, David F; Greenfield, David S; Caprioli, Joseph

2004-02-01

The presently available scanning laser polarimeter (SLP) has a fixed corneal compensator (FCC) that neutralizes corneal birefringence only in eyes with birefringence that matches the population mode. A prototype variable corneal compensator (VCC) provides neutralization of individual corneal birefringence based on individual macular retardation patterns. The aim of this study was to evaluate the relative ability of the SLP with the FCC and with the VCC to discriminate between normal and glaucomatous eyes. Prospective, nonrandomized, comparative case series. Algorithm-generating set consisting of 56 normal eyes and 55 glaucomatous eyes and an independent data set consisting of 83 normal eyes and 56 glaucomatous eyes. Sixteen retardation measurements were obtained with the SLP with the FCC and the VCC from all subjects. Dependency of parameters on age, gender, ethnic origin, and eye side was sought. Logistic regression was used to evaluate how well the various parameters could detect glaucoma. Discriminant functions were generated, and the area under the receiver operating characteristic (ROC) curve was determined. Discrimination between normal and glaucomatous eyes on the basis of single parameters was significantly better with the VCC than with the FCC for 6 retardation parameters: nasal average (P = 0.0003), superior maximum (P = 0.0003), ellipse average (P = 0.002), average thickness (P = 0.003), superior average (P = 0.010), and inferior average (P = 0.010). Discriminant analysis identified the optimal combination of parameters for the FCC and for the VCC. When the discriminant functions were applied to the independent data set, areas under the ROC curve were 0.84 for the FCC and 0.90 for the VCC (P<0.021). When the discriminant functions were applied to a subset of patients with early visual field loss, areas under the ROC curve were 0.82 for the FCC and 0.90 for the VCC (P<0.016). Individual correction for corneal birefringence with the VCC significantly improved the ability of the SLP to distinguish between normal and glaucomatous eyes and enabled detection of patients with early glaucoma.

Association of IL-21 cytokine with severity of primary Sjögren syndrome dry eye.

PubMed

Lim, Sung A; Nam, Doo Hyun; Lee, Jee Hye; Kwok, Seung-Ki; Park, Sung-Hwan; Chung, So-Hyang

2015-03-01

IL-21 plays an important role in primary Sjögren syndrome (SS) pathogenesis. The purpose of this study was to evaluate IL-21 expression in tears and the conjunctiva and to analyze the impact of IL-21 on primary SS dry eyes. Eighty subjects were enrolled in this study: 30 patients with primary SS dry eye (30 eyes); 30 patients with non-SS dry eye (30 eyes), and 20 normal controls. Tear IL-21 levels were measured by flow cytometry, and IL-21 gene expression in the conjunctiva from impression cytology was evaluated by quantitative polymerase chain reaction. Ocular Surface Disease Index, tear film breakup time, Schirmer I test, and ocular surface staining scores were obtained for all patients. Primary SS dry eyes had significantly higher tear IL-21 levels than non-SS dry eyes and normal controls (P < 0.01). In addition, IL-21 gene expression in the conjunctiva was also higher in primary SS dry eyes than in non-SS dry eyes and normal controls (P < 0.01). However, there were no significant differences in IL-21 expression in tears and the conjunctiva between non-SS dry eyes and controls. The tear IL-21 level was significantly correlated with ocular surface stain scores (r = 0.54, P < 0.01) and Schirmer I test values (r = -0.23, P < 0.05) in primary SS dry eyes. Our findings suggest that severity of primary SS dry eye is associated with IL-21.

Circular RNA Expression Profile of Pancreatic Ductal Adenocarcinoma Revealed by Microarray.

PubMed

Li, Haimin; Hao, Xiaokun; Wang, Huimin; Liu, Zhengcai; He, Yong; Pu, Meng; Zhang, Hongtao; Yu, Hengchao; Duan, Juanli; Qu, Shibin

2016-01-01

Circular RNAs (circRNAs) are a special novel type of a stable, diverse and conserved noncoding RNA in mammalian cells. Particularly in cancer, circRNAs have been reported to be widely involved in the physiological/pathological process of life. However, it is unclear whether circRNAs are specifically involved in pancreatic ductal adenocarcinoma (PDAC). We investigated the expression profile of circRNAs in six PDAC cancer samples and paired adjacent normal tissues using microarray. A high-throughput circRNA microarray was used to identify dysregulated circular RNAs in six PDAC patients. Bioinformatic analyses were applied to study these differentially expressed circRNAs. Furthermore, quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to confirm these results. We revealed and confirmed that a number of circRNAs were dysregulated, which suggests a potential role in pancreatic cancer. this study demonstrates that clusters of circRNAs are aberrantly expressed in PDAC compared with normal samples and provides new potential targets for the future treatment of PDAC and novel insights into PDAC biology. © 2016 The Author(s) Published by S. Karger AG, Basel.

Comparisons of Robustness and Sensitivity between Cancer and Normal Cells by Microarray Data

PubMed Central

Chu, Liang-Hui; Chen, Bor-Sen

2008-01-01

Robustness is defined as the ability to uphold performance in face of perturbations and uncertainties, and sensitivity is a measure of the system deviations generated by perturbations to the system. While cancer appears as a robust but fragile system, few computational and quantitative evidences demonstrate robustness tradeoffs in cancer. Microarrays have been widely applied to decipher gene expression signatures in human cancer research, and quantification of global gene expression profiles facilitates precise prediction and modeling of cancer in systems biology. We provide several efficient computational methods based on system and control theory to compare robustness and sensitivity between cancer and normal cells by microarray data. Measurement of robustness and sensitivity by linear stochastic model is introduced in this study, which shows oscillations in feedback loops of p53 and demonstrates robustness tradeoffs that cancer is a robust system with some extreme fragilities. In addition, we measure sensitivity of gene expression to perturbations in other gene expression and kinetic parameters, discuss nonlinear effects in feedback loops of p53 and extend our method to robustness-based cancer drug design. PMID:19259409

Immunohistochemical evidence of ubiquitous distribution of the metalloendoprotease insulin-degrading enzyme (IDE; insulysin) in human non-malignant tissues and tumor cell lines.

PubMed

Weirich, Gregor; Mengele, Karin; Yfanti, Christina; Gkazepis, Apostolos; Hellmann, Daniela; Welk, Anita; Giersig, Cecylia; Kuo, Wen-Liang; Rosner, Marsha Rich; Tang, Wei-Jen; Schmitt, Manfred

2008-11-01

Immunohistochemical evidence of ubiquitous distribution of the metalloprotease insulin-degrading enzyme (IDE; insulysin) in human non-malignant tissues and tumor cells is presented. Immunohistochemical staining was performed on a multi-organ tissue microarray (pancreas, lung, kidney, central/peripheral nervous system, liver, breast, placenta, myocardium, striated muscle, bone marrow, thymus, and spleen) and on a cell microarray of 31 tumor cell lines of different origin, as well as trophoblast cells and normal blood lymphocytes and granulocytes. IDE protein was expressed in all the tissues assessed and all the tumor cell lines except for Raji and HL-60. Trophoblast cells and granulocytes, but not normal lymphocytes, were also IDE-positive.

Immunohistochemical evidence for ubiquitous distribution of metalloendoprotease insulin-degrading enzyme (IDE; insulysin) in human non-malignant tissues and tumor cell lines

PubMed Central

Weirich, Gregor; Mengele, Karin; Yfanti, Christina; Gkazepis, Apostolos; Hellmann, Daniela; Welk, Anita; Giersig, Cecylia; Kuo, Wen-Liang; Rosner, Marsha Rich; Tang, Wei-Jen; Schmitt, Manfred

2013-01-01

Immunohistochemical evidence for ubiquitous distribution of metalloprotease insulin-degrading enzyme (IDE; insulysin) in human non-malignant tissues and tumor cells is presented. Immunohistochemical staining was performed on a multi-organ tissue microarray (pancreas, lung, kidney, central/peripheral nervous system, liver, breast, placenta, myocardium, striated muscle, bone marrow, thymus, spleen) and on a cell microarray encompassing 31 tumor cell lines of different origin plus trophoblast cells, and normal blood lymphocytes and granulocytes. IDE protein is expressed by all of the tissues assessed and in all of the tumor cell lines except Raji and HL-60; trophoblast cells and granulocytes but not normal lymphocytes are also IDE-positive. PMID:18783335

Biomechanics of the Human Posterior Sclera: Age- and Glaucoma-Related Changes Measured Using Inflation Testing

PubMed Central

Coudrillier, Baptiste; Tian, Jing; Alexander, Stephen; Myers, Kristin M.; Quigley, Harry A.; Nguyen, Thao D.

2012-01-01

Purpose. The objective of this study was to measure the biomechanical response of the human posterior sclera in vitro and to estimate the effects of age and glaucoma. Methods. Scleral specimens from 22 donors with no history of glaucoma and 11 donors with a history of glaucoma were excised 3 mm posterior to the equator and affixed to an inflation chamber. Optic nerve cross-sections were graded to determine the presence of axon loss. The time-dependent inflation response was measured in a series of pressure-controlled load–unload tests to 30 mm Hg and creep tests to 15 and 30 mm Hg. Circumferential and meridional strains were computed from the digital image correlation displacements, and midposterior stresses were determined from pressure and deformed geometry. Results. Among normal specimens, older age was predictive of a stiffer response and a thinner sclera. In the age group 75 to 93, diagnosed glaucoma eyes with axon damage were thicker than normal eyes. Both damaged and undamaged glaucoma eyes had a different strain response in the peripapillary sclera characterized by a stiffer meridional response. Undamaged glaucoma eyes had slower circumferential creep rates in the peripapillary sclera than normal eyes. Glaucoma eyes were not different from normal eyes in stresses and strains in the midposterior sclera. Conclusions. The observed differences in the biomechanical response of normal and glaucoma sclera may represent baseline properties that contribute to axon damage, or may be characteristics that result from glaucomatous disease. PMID:22395883

Glaucoma-induced optic disc morphometric changes and glaucoma diagnostic ability of Heidelberg Retina Tomograph II in highly myopic eyes.

PubMed

Mayama, Chihiro; Tsutsumi, Tae; Saito, Hitomi; Asaoka, Ryo; Tomidokoro, Atsuo; Iwase, Aiko; Otani, Shinichiro; Miyata, Kazunori; Araie, Makoto

2014-01-01

This study was performed to first investigate the morphological differences in the optic nerve head between highly myopic non-glaucomatous controls and highly myopic glaucomatous eyes in comparison with the differences between emmetropic non-glaucomatous controls and emmetropic glaucomatous eyes using confocal scanning laser ophthalmoscopy. Further, the ability of the apparatus in glaucoma diagnosis in highly myopic eyes was compared with that in emmetropic eyes. Healthy subjects and age-matched patients with early-stage open-angle glaucoma were divided into two groups: emmetropic eyes (-1.0 to +1.0 diopters) and highly myopic eyes (-12.0 to -5.0 diopters).The participants were comprised of 65 emmetropic normal eyes, 59 emmetropic glaucomatous eyes, 62 highly myopic normal eyes, and 68 highly myopic glaucomatous eyes and eyes with pathologic myopia were carefully excluded. Confocal scanning laser tomographic parameters were compared among all subjects after adjustment for age and disc area. The ROC curves and sensitivity and specificity for glaucoma detection using several clinical methods were then compared between the emmetropic and highly myopic eyes. Rim area, cup/disc area ratio, mean cup depth, and cup shape measure of glaucoma eyes are significantly different from those of normal eyes in both highly myopic eyes and emmetropic eyes. Methodological overestimation of retinal nerve fiber layer cross sectional area due to optic disc tilting was suggested in the highly myopic eyes. The diagnostic performance of glaucoma using several discriminant methods significantly deteriorated in the highly myopic eyes. In the highly myopic glaucomatous eyes, confocal scanning laser tomographic parameters were significantly different from that of non-glaucomatous highly myopic eyes but diagnostic performance of glaucoma was deteriorated than that in emmetropic eyes. These findings demonstrate the utility and limitations of the apparatus in diagnosing glaucoma in highly myopic patients.

Employing image processing techniques for cancer detection using microarray images.

PubMed

Dehghan Khalilabad, Nastaran; Hassanpour, Hamid

2017-02-01

Microarray technology is a powerful genomic tool for simultaneously studying and analyzing the behavior of thousands of genes. The analysis of images obtained from this technology plays a critical role in the detection and treatment of diseases. The aim of the current study is to develop an automated system for analyzing data from microarray images in order to detect cancerous cases. The proposed system consists of three main phases, namely image processing, data mining, and the detection of the disease. The image processing phase performs operations such as refining image rotation, gridding (locating genes) and extracting raw data from images the data mining includes normalizing the extracted data and selecting the more effective genes. Finally, via the extracted data, cancerous cell is recognized. To evaluate the performance of the proposed system, microarray database is employed which includes Breast cancer, Myeloid Leukemia and Lymphomas from the Stanford Microarray Database. The results indicate that the proposed system is able to identify the type of cancer from the data set with an accuracy of 95.45%, 94.11%, and 100%, respectively. Copyright © 2017 Elsevier Ltd. All rights reserved.

An efficient method to identify differentially expressed genes in microarray experiments

PubMed Central

Qin, Huaizhen; Feng, Tao; Harding, Scott A.; Tsai, Chung-Jui; Zhang, Shuanglin

2013-01-01

Motivation Microarray experiments typically analyze thousands to tens of thousands of genes from small numbers of biological replicates. The fact that genes are normally expressed in functionally relevant patterns suggests that gene-expression data can be stratified and clustered into relatively homogenous groups. Cluster-wise dimensionality reduction should make it feasible to improve screening power while minimizing information loss. Results We propose a powerful and computationally simple method for finding differentially expressed genes in small microarray experiments. The method incorporates a novel stratification-based tight clustering algorithm, principal component analysis and information pooling. Comprehensive simulations show that our method is substantially more powerful than the popular SAM and eBayes approaches. We applied the method to three real microarray datasets: one from a Populus nitrogen stress experiment with 3 biological replicates; and two from public microarray datasets of human cancers with 10 to 40 biological replicates. In all three analyses, our method proved more robust than the popular alternatives for identification of differentially expressed genes. Availability The C++ code to implement the proposed method is available upon request for academic use. PMID:18453554

Evidence for object permanence in the smooth-pursuit eye movements of monkeys.

PubMed

Churchland, Mark M; Chou, I-Han; Lisberger, Stephen G

2003-10-01

We recorded the smooth-pursuit eye movements of monkeys in response to targets that were extinguished (blinked) for 200 ms in mid-trajectory. Eye velocity declined considerably during the target blinks, even when the blinks were completely predictable in time and space. Eye velocity declined whether blinks were presented during steady-state pursuit of a constant-velocity target, during initiation of pursuit before target velocity was reached, or during eye accelerations induced by a change in target velocity. When a physical occluder covered the trajectory of the target during blinks, creating the impression that the target moved behind it, the decline in eye velocity was reduced or abolished. If the target was occluded once the eye had reached target velocity, pursuit was only slightly poorer than normal, uninterrupted pursuit. In contrast, if the target was occluded during the initiation of pursuit, while the eye was accelerating toward target velocity, pursuit during occlusion was very different from normal pursuit. Eye velocity remained relatively stable during target occlusion, showing much less acceleration than normal pursuit and much less of a decline than was produced by a target blink. Anticipatory or predictive eye acceleration was typically observed just prior to the reappearance of the target. Computer simulations show that these results are best understood by assuming that a mechanism of eye-velocity memory remains engaged during target occlusion but is disengaged during target blinks.

Intraocular lens based on double-liquid variable-focus lens.

PubMed

Peng, Runling; Li, Yifan; Hu, Shuilan; Wei, Maowei; Chen, Jiabi

2014-01-10

In this work, the crystalline lens in the Gullstrand-Le Grand human eye model is replaced by a double-liquid variable-focus lens, the structure data of which are based on theoretical analysis and experimental results. When the pseudoaphakic eye is built in Zemax, aspherical surfaces are introduced to the double-liquid variable-focus lens to reduce the axial spherical aberration existent in the system. After optimization, the zoom range of the pseudoaphakic eye greatly exceeds that of normal human eyes, and the spot size on an image plane basically reaches the normal human eye's limit of resolution.

EFFECTS OF TOPICAL CORTICOSTEROID ADMINISTRATION ON INTRAOCULAR PRESSURE IN NORMAL AND GLAUCOMATOUS CATS

PubMed Central

Gosling, Allyson A; Kiland, Julie A; Rutkowski, Lauren E; Hoefs, Adam; Ellinwood, N Matthew; McLellan, Gillian J

2016-01-01

Objective to determine the effect of topical corticosteroid (CCS) therapy on intraocular pressure (IOP) in normal cats and cats with primary feline congenital glaucoma (FCG). Animals studied 5 normal and 11 FCG cats were studied in 2 cohorts. Procedures IOP was measured by a single, masked observer, once daily 3–5 days/week throughout the course of CCS treatment and for up to 11 days after treatment discontinuation. One eye per cat was randomly assigned for treatment twice daily with CCS; Balanced salt solution (BSS) applied to the contralateral eye, served as a control. Differences between eyes and between weeks of the study period were calculated for each cat. A positive response to CCS was defined as a consistent >15% or >25% higher IOP in the treated relative to control eye in normal and FCG cats, respectively. Results 8/11 FCG cats responded to topical CCS after 1–5 weeks of treatment with an increase in IOP relative to the untreated eye (maximum IOP discrepancy of 56 mmHg). 2/5 normal cats responded to topical CCS with appreciable but clinically unimportant increase in IOP in the treated eye (maximum IOP discrepancy of 6.4 mmHg). Conclusions our data indicate that the incidence of steroid induced IOP elevation in cats is lower than previously published feline studies suggest. Cats with pre-existing compromise in aqueous humor outflow may show a greater, clinically relevant response to topical CCS than normal cats. PMID:26876736

Identification of candidate genes in osteoporosis by integrated microarray analysis.

PubMed

Li, J J; Wang, B Q; Fei, Q; Yang, Y; Li, D

2016-12-01

In order to screen the altered gene expression profile in peripheral blood mononuclear cells of patients with osteoporosis, we performed an integrated analysis of the online microarray studies of osteoporosis. We searched the Gene Expression Omnibus (GEO) database for microarray studies of peripheral blood mononuclear cells in patients with osteoporosis. Subsequently, we integrated gene expression data sets from multiple microarray studies to obtain differentially expressed genes (DEGs) between patients with osteoporosis and normal controls. Gene function analysis was performed to uncover the functions of identified DEGs. A total of three microarray studies were selected for integrated analysis. In all, 1125 genes were found to be significantly differentially expressed between osteoporosis patients and normal controls, with 373 upregulated and 752 downregulated genes. Positive regulation of the cellular amino metabolic process (gene ontology (GO): 0033240, false discovery rate (FDR) = 1.00E + 00) was significantly enriched under the GO category for biological processes, while for molecular functions, flavin adenine dinucleotide binding (GO: 0050660, FDR = 3.66E-01) and androgen receptor binding (GO: 0050681, FDR = 6.35E-01) were significantly enriched. DEGs were enriched in many osteoporosis-related signalling pathways, including those of mitogen-activated protein kinase (MAPK) and calcium. Protein-protein interaction (PPI) network analysis showed that the significant hub proteins contained ubiquitin specific peptidase 9, X-linked (Degree = 99), ubiquitin specific peptidase 19 (Degree = 57) and ubiquitin conjugating enzyme E2 B (Degree = 57). Analysis of gene function of identified differentially expressed genes may expand our understanding of fundamental mechanisms leading to osteoporosis. Moreover, significantly enriched pathways, such as MAPK and calcium, may involve in osteoporosis through osteoblastic differentiation and bone formation.Cite this article: J. J. Li, B. Q. Wang, Q. Fei, Y. Yang, D. Li. Identification of candidate genes in osteoporosis by integrated microarray analysis. Bone Joint Res 2016;5:594-601. DOI: 10.1302/2046-3758.512.BJR-2016-0073.R1. © 2016 Fei et al.

Identification of cornifelin and early growth response-1 gene as novel biomarkers for in vitro eye irritation using a 3D reconstructed human cornea model MCTT HCE™.

PubMed

Choi, Seunghye; Lee, Miri; Lee, Su-Hyon; Jung, Haeng-Sun; Kim, Seol-Yeong; Chung, Tae-Young; Choe, Tae-boo; Chun, Young-Jin; Lim, Kyung-Min

2015-09-01

Evaluation of the eye irritation is essential in the development of new cosmetic products. Draize rabbit eye irritation test has been widely used in which chemicals are directly applied to rabbit eye, and the symptoms and signs of eyes are scored. However, due to the invasive procedure, it causes substantial pain and discomfort to animals. Recently, we reported in vitro eye irritation test method using a 3D human corneal epithelial model (MCTT HCE™) which is reconstructed from remaining human tissues after a corneal transplantation. This model exhibited an excellent predictive capacity for 25 reference chemicals (sensitivity 100%, specificity 77% and accuracy 88% vs. GHS). To improve the test performance, we explored new biomarkers for the eye irritation through transcriptomic approach. Three surfactants were selected as model eye irritants that include sodium lauryl sulfate, benzalkonium chloride and triton X-100. After test chemicals were treated, we investigated differentially expressed genes through a whole-gene microarray (Affymetrix GeneChip(®) Human Gene 2.0 ST Array, 48,000 probes). As a result, we identified that mRNAs of cornifelin (CNFN), a constituent of the insoluble cornified cell envelope of stratified squamous epithelia, and early growth response-1 (EGR1), a nuclear transcriptional regulator, were significantly up-regulated by all three irritants. Up-regulation of CNFN and EGR1 was further confirmed by Q-RT-PCR, and immunohistochemistry revealed increased level of CNFN in irritant-treated tissues, supporting the relevance of CNFN and EGR1 as new biomarkers for eye irritation.

Subclinical keratoconus detection by pattern analysis of corneal and epithelial thickness maps with optical coherence tomography

PubMed Central

Li, Yan; Chamberlain, Winston; Tan, Ou; Brass, Robert; Weiss, Jack L.; Huang, David

2016-01-01

PURPOSE To screen for subclinical keratoconus by analyzing corneal, epithelial, and stromal thickness map patterns with Fourier-domain optical coherence tomography (OCT). SETTING Four centers in the United States. DESIGN Cross-sectional observational study. METHODS Eyes of normal subjects, subclinical keratoconus eyes, and the topographically normal eye of a unilateral keratoconus patient were studied. Corneas were scanned using a 26 000 Hz Fourier-domain OCT system (RTVue). Normal subjects were divided into training and evaluation groups. Corneal, epithelial, and stromal thickness maps and derived diagnostic indices, including pattern standard deviation (PSD) variables and pachymetric map–based keratoconus risk scores were calculated from the OCT data. Area under the receiver operating characteristic curve (AUC) analysis was used to evaluate the diagnostic accuracy of the indices. RESULTS The study comprised 150 eyes of 83 normal subjects, 50 subclinical keratoconus eyes of 32 patients, and 1 topographically normal eye of a unilateral keratoconus patient. Subclinical keratoconus was characterized by inferotemporal thinning of the cornea, epithelium, and stroma. The PSD values for corneal (P < .001), epithelial (P < .001), and stromal (P = .049) thickness maps were all significantly higher in subclinical keratoconic eyes than in the normal group. The diagnostic accuracy was significantly higher for PSD variables (pachymetric PSD, AUC = 0.941; epithelial PSD, AUC = 0.985; stromal PSD, AUC = 0.924) than for the pachymetric map–based keratoconus risk score (AUC = 0.735). CONCLUSIONS High-resolution Fourier-domain OCT could map corneal, epithelial, and stromal thicknesses. Corneal and sublayer thickness changes in subclinical keratoconus could be detected with high accuracy using PSD variables. These new diagnostic variables might be useful in the detection of early keratoconus. PMID:27026454

Corneal thickness in dry eyes in an Iraqi population.

PubMed

Ali, Noora Mauwafak; Hamied, Furkaan M; Farhood, Qasim K

2017-01-01

Dry eye disorder is a multifactorial disease of the tears and ocular surface that results in discomfort and visual disturbance. Corneal pachymetry becomes increasingly important in refractive surgery, for the accurate assessment of intraocular pressure, and in the preoperative assessment of other ocular surgeries. To assess the effect of dry eye disorder on the central corneal thickness (CCT) by comparing with CCT of normal eyes of age-matched individuals. The total number of eyes examined was 280 (140 dry eyes from 70 patients and 140 normal eyes from 70 individuals). Pentacam (Scheimpflug imaging system) was used for measuring the CCT of all eyes. Patients with dry eye syndrome had significantly lower CCT compared to the control group ( P <0.01). Its mean was 536.5 versus 561.3, respectively. CCT of dry eyes was significantly reduced when compared with age- and gender-matched population. This result can be attributed to chronic desiccation by the inflammatory mediators in dry eyes, leading to corneal thinning.

[Neuroprotective effect of erigeron breviscapus (vant) hand-mazz on NMDA-induced retinal neuron injury in the rats].

PubMed

Shi, Jingming; Jiag, Youqin; Liu, Xuyang

2004-07-01

To investigate if Erigeron Breviscapus (vant) Hand-Mazz (EBHM) has a neuroprotective effect against NMDA-induced neuron death in retinal ganglion cell layer (RGCL). Sixty healthy SD rats were randomly divided into four groups. 6 animals were in normal control group (group A). The others were divided as group B (EBHM group), group C (normal saline+NMDA group), group D (EBHM+NMDA group). Each group has 18 rats. 10 nmol NMDA was chosen for intravitreal injection to cause partial damage of the neurons in RGCL in the right eyes of Groups C and D. Same volume PBS was intravitreal injected in the left eyes as self-control. Groups B and D were pre-treated intraperitoneally with 6% EBHM solution at a dose of 15 mg x 100 g(-1) x d(-1) seven days before and after NMDA treatment. Group C were administrated intraperitoneally with 0.9% normal saline at the same time of EBHM injection. Rats were sacrificed in 4, 7, 14 days after NMDA treatment. Flat preparation of whole retinas were stained with 0.5% cresyl violet and neuron counting in RGCL from both eyes. Each subgroup has 6 rats. There was no significant difference between the right eye and the left eye of neuron counting from RGCL in normal control group (group A) (P=0.200). There was no significant difference between normal control group and EBHM group either in the right eyes or in the left eye in 4 days, 7 days and 14 days respectively after intravitreal injection of 10 nmol NMDA in group C and group D. (P=0.636, P=0.193). Neuron counting from RGCL of group C and group D were significant decreased in the NMDA-treated eyes in 4 days, 7 days and 14 days after intravitreal injection (P < 0.001). There ws no significant difference between self-control eyes and normal control group (P > 0.05). Neuron counting was significantly higher in the EBHM+NMDA group than normal saline+NMDA group at 14 days after intraviteal injection (P=0.044). However,it is obvious that the difference was still significant between normal control group and EBHM+NMDA group (P < 0.05). EBHM has no effect on neuron counting of RGCL when administered alone in normal rats. It is suggested that EBHM has partial protective effect on NMDA-induced neuron loss in RGCL in the rat.

Postural stability of preoperative acoustic neuroma patients assessed by sway magnetometry: are they unsteady?

PubMed

Collins, Melanie M; Johnson, Ian J M; Clifford, Elaine; Birchall, John P; O'Donoghue, Gerald M

2003-04-01

The objective was to evaluate the preoperative postural stability of acoustic neuroma patients using sway magnetometry. Prospective two-center study. Fifty-one patients (mean age, 53 years) diagnosed with unilateral acoustic neuroma on magnetic resonance imaging at two tertiary referral centers were studied. Preoperatively, each patient had sway patterns (with eyes open and with eyes closed, and standing on foam) recorded for 120 seconds by sway magnetometry. Path length for 30 seconds was calculated. The Romberg coefficient (path length with eyes open divided by path length with eyes closed) was calculated. Forty-four percent of patients had abnormal path lengths with eyes open, and 49% with eyes closed. The Romberg coefficients were significantly lower than normal (P <.001; 95% CI, 0.19-0.87). Mean Romberg coefficient was 0.59 (normal value = 0.73), and all patients had a coefficient of less than 1. Half of preoperative acoustic neuroma patients are unsteady, exhibiting abnormal sway patterns based on path length measurements. The increase in sway path length demonstrable in normal subjects with eyes closed was significantly exaggerated in patients with acoustic neuroma.

The effects of topical aqueous sirolimus on tear production in normal dogs and dogs with refractory dry eye.

PubMed

Spatola, Ronald; Nadelstein, Brad; Berdoulay, Andrew; English, Robert V

2018-05-01

To evaluate the effect of twice daily aqueous 0.02% sirolimus drops on tear production in normal dogs and dogs with refractory keratoconjunctivitis sicca (KCS). Two groups of dogs were studied. Ten normal dogs with no signs of ocular disease were administered topical 0.02% sirolimus ophthalmic solution in right eye, and a vehicle control in the left eye twice daily for 4 weeks. Complete ophthalmic examinations, including Schirmer tear test were performed weekly. Eighteen dogs with refractory KCS were randomly assigned to receive 0.02% sirolumus ophthalmic solution or 0.02% tacrolimus ophthalmic solution twice daily. Complete ophthalmic examinations were was performed at 2 and 6 weeks following treatment. Tear production in the sirolimus-treated eyes of normal dogs was greater when compared to vehicle controls with a mean difference over all time points of 3.46 mm (95% CI 1.17, 5.75; P = 0.006). After 4 weeks of treatment, the mean difference was 5 mm (95% CI 1.95, 8.05; P = 0.002). In dogs with refractory dry eye, 37.5% of eyes treated with sirolimus exhibited increased tear production >4 mm/min after 6 weeks of treatment, compared to 20% of eyes receiving tacrolimus (P = 0.433). One normal dog experienced topical irritation to both sirolimus and vehicle-treatment. Side effects were not reported in any treated eyes with chronic KCS. Topical 0.02% sirolimus might be an alternative treatment for canine patients with keratoconjunctivits sicca. The drug appears safe when applied topically in an aqueous suspension for up to 6 weeks. While initial results are promising, further studies are warranted. © 2017 American College of Veterinary Ophthalmologists.

Maximal subtotal extirpation of the horizontal rectus extraocular muscles for the treatment of nystagmus with no null point. A report of four successful human cases.

PubMed

Sinskey, Robert M; Eshete, Almaz

2002-01-01

To evaluate the visual and restoration of normal appearance results of maximal excision of the horizontal rectus muscles in nystagmus patients. Menelik II Hospital, Addis Ababa, Ethiopia and the Sinskey Eye Institute, Santa Monica, California. The medial and lateral rectus muscles were extirpated as far back as possible with an enucleation snare in four patients with horizontal nystagmus. A complete eye examination was performed pre- and postoperatively. Using a camcorder, ocular movements were recorded before surgery, and at postop; days 1 and 40, and months 1, 3 and 10. All four patients had a marked reduction in both abnormal and normal horizontal eye movement, and improvement in objective visual acuity. Postoperative residual intermittent fine horizontal movement was recorded in the left eye in a 6 year old and in both eyes of a 41 year old patient. A residual rotary component was recorded in a 15 year-old patient. The 6 and 9 year-old patients each developed a moderate exotropia. The 15 and 41 year-old patients maintained binocular fusion with some residual ability to converge. Vision increased subjectively in all cases. Subtotal myectomy of the horizontal muscles in horizontal nystagmus with no null point was very effective in improving and/or eliminating horizontal eye movement. Restoration of normal or near normal appearance and improvement in visual acuity occurred in all cases. None of the patients complained of their loss of horizontal gaze and eye movement. More complete myectomy of the muscles should produce total elimination of both normal and abnormal horizontal eye movement including nystagmus.

Second-generation corneal deformation signal waveform analysis in normal, forme fruste keratoconic, and manifest keratoconic corneas after statistical correction for potentially confounding factors.

PubMed

Zhang, Lijun; Danesh, Jennifer; Tannan, Anjali; Phan, Vivian; Yu, Fei; Hamilton, D Rex

2015-10-01

To evaluate the difference in corneal biomechanical waveform parameters between manifest keratoconus, forme fruste keratoconus, and healthy eyes with a second-generation biomechanical waveform analyzer (Ocular Response Analyzer 2). Jules Stein Eye Institute, University of California, Los Angeles, California, USA. Retrospective chart review. The biomechanical waveform analyzer was used to obtain corneal hysteresis (CH), corneal resistance factor (CRF), and 37 biomechanical waveform parameters in manifest keratoconus eyes, forme fruste keratoconus eyes, and healthy eyes. Useful distinguishing parameters were found using t tests and a multivariable logistic regression model with stepwise variable selection. Potential confounders were controlled for. The study included 68 manifest keratoconus eyes, 64 forme fruste keratoconus eyes, and 249 healthy eyes. There was a statistical difference in the mean CRF between the normal group (10.2 mm Hg ± 1.7 [SD]) and keratoconus group (6.3 ± 1.9 mm Hg) (P = .003), and between the normal group and the forme fruste keratoconus group (7.8 ± 1.4 mm Hg) (P < .0001). There was no statistical difference in the mean CH between the normal group and the keratoconus group or the forme fruste keratoconus group. The CRF, height of peak 1 (P1) (P = .001), downslope of P1 (dslope1) (P = .027), upslope of peak 2 (P2) (P = .004), and downslope of P2 (P = .006) distinguished the normal group from the keratoconus groups. The CRF, downslope of P2 derived from upper 50% of applanation peak (P = .035), dslope1 (P = .014), and upslope of P1 (P = .008) distinguished the normal group from the forme fruste keratoconus group. Differences in multiple biomechanical waveform parameters can differentiate between healthy and diseased conditions and might improve early diagnosis of keratoconus and forme fruste keratoconus. No author has a financial or proprietary interest in any material or method mentioned. Copyright © 2015 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

Microarray analysis of retinal gene expression in Egr-1 knockout mice

PubMed Central

Schippert, Ruth; Schaeffel, Frank

2009-01-01

Purpose We found earlier that 42 day-old Egr-1 knockout mice had longer eyes and a more myopic refractive error compared to their wild-types. To identify genes that could be responsible for the temporarily enhanced axial eye growth, a microarray analysis was performed in knockout and wild-type mice at the postnatal ages of 30 and 42 days. Methods The retinas of homozygous and wild-type Egr-1 knockout mice (Taconic, Ry, Denmark) were prepared for RNA isolation (RNeasy Mini Kit, Qiagen) at the age of 30 or 42 days, respectively (n=12 each). Three retinas were pooled and labeled cRNA was made. The samples were hybridized to Affymetrix GeneChip Mouse Genome 430 2.0 Arrays. Hybridization signals were calculated using GC-RMA normalization. Genes were identified as differentially expressed if they showed a fold-change (FC) of at least 1.5 and a p-value <0.05. A false-discovery rate of 5% was applied. Ten genes with potential biologic relevance were examined further with semiquantitative real-time RT–PCR. Results Comparing mRNA expression levels between wild-type and homozygous Egr-1 knockout mice, we found 73 differentially expressed genes at the age of 30 days and 135 genes at the age of 42 days. Testing for differences in gene expression between the two ages (30 versus 42 days), 54 genes were differently expressed in wild-type mice and 215 genes in homozygous animals. Based on three networks proposed by Ingenuity pathway analysis software, nine differently expressed genes in the homozygous Egr-1 knockout mice were chosen for further validation by real-time RT–PCR, three genes in each network. In addition, the gene that was most prominently regulated in the knockout mice, compared to wild-type, at both 30 days and 42 days of age (protocadherin beta-9 [Pcdhb9]), was tested with real-time RT–PCR. Changes in four of the ten genes could be confirmed by real-time RT–PCR: nuclear prelamin A recognition factor (Narf), oxoglutarate dehydrogenase (Ogdh), selenium binding protein 1 (Selenbp1), and Pcdhb9. Except for Pcdhb9, the genes whose mRNA expression levels were validated were listed in one of the networks proposed by Ingenuity pathway analysis software. In addition to these genes, the software proposed several key-regulators which did not change in our study: retinoic acid, vascular endothelial growth factor A (VEGF-A), FBJ murine osteosarcoma viral oncogene homolog (cFos), and others. Conclusions Identification of genes that are differentially regulated during the development period between postnatal day 30 (when both homozygous and wild-type mice still have the same axial length) and day 42 (where the difference in eye length is apparent) could improve the understanding of mechanisms for the control of axial eye growth and may lead to potential targets for pharmacological intervention. With the aid of pathway-analysis software, a coarse picture of possible biochemical pathways could be generated. Although the mRNA expression levels of proteins proposed by the software, like VEGF, FOS, retinoic acid (RA) receptors, or cellular RA binding protein, did not show any changes in our experiment, these molecules have previously been implicated in the signaling cascades controlling axial eye growth. According to the pathway-analysis software, they represent links between several proteins whose mRNA expression was changed in our study. PMID:20019881

Microarray analysis of retinal gene expression in Egr-1 knockout mice.

PubMed

Schippert, Ruth; Schaeffel, Frank; Feldkaemper, Marita Pauline

2009-12-10

We found earlier that 42 day-old Egr-1 knockout mice had longer eyes and a more myopic refractive error compared to their wild-types. To identify genes that could be responsible for the temporarily enhanced axial eye growth, a microarray analysis was performed in knockout and wild-type mice at the postnatal ages of 30 and 42 days. The retinas of homozygous and wild-type Egr-1 knockout mice (Taconic, Ry, Denmark) were prepared for RNA isolation (RNeasy Mini Kit, Qiagen) at the age of 30 or 42 days, respectively (n=12 each). Three retinas were pooled and labeled cRNA was made. The samples were hybridized to Affymetrix GeneChip Mouse Genome 430 2.0 Arrays. Hybridization signals were calculated using GC-RMA normalization. Genes were identified as differentially expressed if they showed a fold-change (FC) of at least 1.5 and a p-value <0.05. A false-discovery rate of 5% was applied. Ten genes with potential biologic relevance were examined further with semiquantitative real-time RT-PCR. Comparing mRNA expression levels between wild-type and homozygous Egr-1 knockout mice, we found 73 differentially expressed genes at the age of 30 days and 135 genes at the age of 42 days. Testing for differences in gene expression between the two ages (30 versus 42 days), 54 genes were differently expressed in wild-type mice and 215 genes in homozygous animals. Based on three networks proposed by Ingenuity pathway analysis software, nine differently expressed genes in the homozygous Egr-1 knockout mice were chosen for further validation by real-time RT-PCR, three genes in each network. In addition, the gene that was most prominently regulated in the knockout mice, compared to wild-type, at both 30 days and 42 days of age (protocadherin beta-9 [Pcdhb9]), was tested with real-time RT-PCR. Changes in four of the ten genes could be confirmed by real-time RT-PCR: nuclear prelamin A recognition factor (Narf), oxoglutarate dehydrogenase (Ogdh), selenium binding protein 1 (Selenbp1), and Pcdhb9. Except for Pcdhb9, the genes whose mRNA expression levels were validated were listed in one of the networks proposed by Ingenuity pathway analysis software. In addition to these genes, the software proposed several key-regulators which did not change in our study: retinoic acid, vascular endothelial growth factor A (VEGF-A), FBJ murine osteosarcoma viral oncogene homolog (cFos), and others. Identification of genes that are differentially regulated during the development period between postnatal day 30 (when both homozygous and wild-type mice still have the same axial length) and day 42 (where the difference in eye length is apparent) could improve the understanding of mechanisms for the control of axial eye growth and may lead to potential targets for pharmacological intervention. With the aid of pathway-analysis software, a coarse picture of possible biochemical pathways could be generated. Although the mRNA expression levels of proteins proposed by the software, like VEGF, FOS, retinoic acid (RA) receptors, or cellular RA binding protein, did not show any changes in our experiment, these molecules have previously been implicated in the signaling cascades controlling axial eye growth. According to the pathway-analysis software, they represent links between several proteins whose mRNA expression was changed in our study.

Protein Microarray Analysis in Patients With Asthma*

PubMed Central

Kim, Hyo-Bin; Kim, Chang-Keun; Iijima, Koji; Kobayashi, Takao; Kita, Hirohito

2010-01-01

Background Microarray technology offers a new opportunity to gain insight into global gene and protein expression profiles in asthma. To identify novel factors produced in the asthmatic airway, we analyzed sputum samples by using a membrane-based human cytokine microarray technology in patients with bronchial asthma (BA). Methods Induced sputum was obtained from 28 BA subjects, 20 nonasthmatic atopic control (AC) subjects, and 38 nonasthmatic nonatopic normal control (NC) subjects. The microarray samples of subjects were randomly selected from nine BA subjects, three AC subjects, and six NC subjects. Sputum supernatants were analyzed using a custom human cytokine array (RayBio Custom Human Cytokine Array; RayBiotech; Norcross, GA) designed to analyze 79 specific cytokines simultaneously. The levels of growth-regulated oncogene (GRO)-α, eotaxin-2, and pulmonary and activation-regulated chemokine (PARC)/CCL18 were measured by sandwich enzyme-linked immunosorbent assays (ELISAs), and eosinophil-derived neurotoxin (EDN) was measured by radioimmunoassay. Results By microarray, the signal intensities for GRO-α, eotaxin-2, and PARC were significantly higher in BA subjects than in AC and NC subjects (p = 0.036, p = 0.042, and p = 0.033, respectively). By ELISA, the sputum PARC protein levels were significantly higher in BA subjects than in AC and NC subjects (p < 0.0001). Furthermore, PARC levels correlated significantly with sputum eosinophil percentages (r = 0.570, p < 0.0001) and the levels of EDN(r = 0.633, p < 0.0001), the regulated upon activation, normal T cell expressed and secreted cytokine (r = 0.440, p < 0.001), interleukin-4 (r = 0.415, p < 0.01), and interferon-γ (r = 0.491, p < 0.001). Conclusions By a nonbiased screening approach, a chemokine, PARC, is elevated in sputum specimens from patients with asthma. PARC may play important roles in development of airway eosinophilic inflammation in asthma. PMID:19017877

Microarray platform affords improved product analysis in mammalian cell growth studies

PubMed Central

Li, Lingyun; Migliore, Nicole; Schaefer, Eugene; Sharfstein, Susan T.; Dordick, Jonathan S.; Linhardt, Robert J.

2014-01-01

High throughput (HT) platforms serve as cost-efficient and rapid screening method for evaluating the effect of cell culture conditions and screening of chemicals. The aim of the current study was to develop a high-throughput cell-based microarray platform to assess the effect of culture conditions on Chinese hamster ovary (CHO) cells. Specifically, growth, transgene expression and metabolism of a GS/MSX CHO cell line, which produces a therapeutic monoclonal antibody, was examined using microarray system in conjunction with conventional shake flask platform in a non-proprietary medium. The microarray system consists of 60 nl spots of cells encapsulated in alginate and separated in groups via an 8-well chamber system attached to the chip. Results show the non-proprietary medium developed allows cell growth, production and normal glycosylation of recombinant antibody and metabolism of the recombinant CHO cells in both the microarray and shake flask platforms. In addition, 10.3 mM glutamate addition to the defined base media results in lactate metabolism shift in the recombinant GS/MSX CHO cells in the shake flask platform. Ultimately, the results demonstrate that the high-throughput microarray platform has the potential to be utilized for evaluating the impact of media additives on cellular processes, such as, cell growth, metabolism and productivity. PMID:24227746

Upregulation of regulator of G-protein signaling 2 in the sclera of a form deprivation myopic animal model

PubMed Central

Zou, Leilei; Liu, Rui; Zhang, Xiaohui; Chu, Renyuan; Dai, Jinhui; Zhou, Hao

2014-01-01

Purpose Scleral remodeling is an important mechanism underlying the development of myopia. Atropine, an antagonist of G protein-coupled muscarinic receptors, is currently used as an off-label treatment for myopia. Regulator of G-protein signaling 2 (RGS2) functions as an intracellular selective inhibitor of muscarinic receptors. In this study we measured scleral RGS2 expression and scleral remodeling in an animal model of myopia in the presence or absence of atropine treatment. Methods Guinea pigs were assigned to four groups: normal (free of form deprivation), form deprivation myopia (FDM) for 4 weeks, FDM treated with saline, and FDM treated with atropine. Biometric measurements were then performed. RGS2 expression levels and scleral remodeling, including scleral thickness and collagen type I expression, were compared among the four groups. Results Compared with normal eyes and contralateral control eyes, the FDM eyes had the most prominent changes in refraction, axial length, and scleral remodeling, indicating myopia. There was no significant difference between control and normal eyes. Hematoxylin and eosin staining showed that the scleral thickness was significantly thinner in the posterior pole region of FDM eyes compared to normal eyes. Real-time PCR and western blot analysis showed a significant decrease in posterior scleral collagen type I mRNA and protein expression in the FDM eyes compared to the normal eyes. The FDM eyes also had increased levels of RGS2 mRNA and protein expression in the sclera. Atropine treatment attenuated the FDM-induced changes in refraction, axial length, and scleral remodeling. Interestingly, atropine treatment significantly increased collagen type I mRNA expression but decreased RGS2 mRNA and protein expression in the sclera of the FDM eyes. Conclusions We identified a significant RGS2 upregulation and collagen type I downregulation in the sclera of FDM eyes, which could be partially attenuated by atropine treatment. Our data suggest that targeting dysregulated RGS2 may provide a novel strategy for development of therapeutic agents to suppress myopia progression. PMID:25018620

Assessment of corneal epithelial thickness in dry eye patients.

PubMed

Cui, Xinhan; Hong, Jiaxu; Wang, Fei; Deng, Sophie X; Yang, Yujing; Zhu, Xiaoyu; Wu, Dan; Zhao, Yujin; Xu, Jianjiang

2014-12-01

To investigate the features of corneal epithelial thickness topography with Fourier-domain optical coherence tomography (OCT) in dry eye patients. In this cross-sectional study, 100 symptomatic dry eye patients and 35 normal subjects were enrolled. All participants answered the ocular surface disease index questionnaire and were subjected to OCT, corneal fluorescein staining, tear breakup time, Schirmer 1 test without anesthetic (S1t), and meibomian morphology. Several epithelium statistics for each eye, including central, superior, inferior, minimum, maximum, minimum - maximum, and map standard deviation, were averaged. Correlations of epithelial thickness with the symptoms of dry eye were calculated. The mean (±SD) central, superior, and inferior corneal epithelial thickness was 53.57 (±3.31) μm, 52.00 (±3.39) μm, and 53.03 (±3.67) μm in normal eyes and 52.71 (±2.83) μm, 50.58 (±3.44) μm, and 52.53 (±3.36) μm in dry eyes, respectively. The superior corneal epithelium was thinner in dry eye patients compared with normal subjects (p = 0.037), whereas central and inferior epithelium were not statistically different. In the dry eye group, patients with higher severity grades had thinner superior (p = 0.017) and minimum (p < 0.001) epithelial thickness, more wide range (p = 0.032), and greater deviation (p = 0.003). The average central epithelial thickness had no correlation with tear breakup time, S1t, or the severity of meibomian glands, whereas average superior epithelial thickness positively correlated with S1t (r = 0.238, p = 0.017). Fourier-domain OCT demonstrated that the thickness map of the dry eye corneal epithelium was thinner than normal eyes in the superior region. In more severe dry eye disease patients, the superior and minimum epithelium was much thinner, with a greater range of map standard deviation.

Estimating gene function with least squares nonnegative matrix factorization.

PubMed

Wang, Guoli; Ochs, Michael F

2007-01-01

Nonnegative matrix factorization is a machine learning algorithm that has extracted information from data in a number of fields, including imaging and spectral analysis, text mining, and microarray data analysis. One limitation with the method for linking genes through microarray data in order to estimate gene function is the high variance observed in transcription levels between different genes. Least squares nonnegative matrix factorization uses estimates of the uncertainties on the mRNA levels for each gene in each condition, to guide the algorithm to a local minimum in normalized chi2, rather than a Euclidean distance or divergence between the reconstructed data and the data itself. Herein, application of this method to microarray data is demonstrated in order to predict gene function.

Ability of Cirrus™ HD-OCT Optic Nerve Head Parameters to Discriminate Normal from Glaucomatous Eyes

PubMed Central

Mwanza, Jean-Claude; Oakley, Jonathan D; Budenz, Donald L; Anderson, Douglas R

2010-01-01

Purpose To determine the ability of optic nerve head (ONH) parameters measured with spectral domain Cirrus™ HD-OCT to discriminate between normal and glaucomatous eyes and to compare them to the discriminating ability of peripapillary retinal nerve fiber layer (RNFL) thickness measurements performed with Cirrus™ HD-OCT. Design Evaluation of diagnostic test or technology. Participants Seventy-three subjects with glaucoma and one hundred and forty-six age-matched normal subjects. Methods Peripapillary ONH parameters and RNFL thickness were measured in one randomly selected eye of each participant within a 200×200 pixel A-scan acquired with Cirrus™ HD-OCT centered on the ONH. Main Outcome Measures ONH topographic parameters, peripapillary RNFL thickness, and the area under receiver operating characteristic curves (AUCs). Results For distinguishing normal from glaucomatous eyes, regardless of disease stage, the six best parameters (expressed as AUC) were vertical rim thickness (VRT, 0.963), rim area (RA, 0.962), RNFL thickness at clock-hour 7 (0.957), RNFL thickness of the inferior quadrant (0.953), vertical cup-to-disc ratio (VCDR, 0.951) and average RNFL thickness (0.950). The AUC for distinguishing between normal and eyes with mild glaucoma was greatest for RNFL thickness of clock-hour 7 (0.918), VRT (0.914), RA (0.912), RNFL thickness of inferior quadrant (0.895), average RNFL thickness (0.893) and VCDR (0.890). There were no statistically significant differences between AUCs for the best ONH parameters and RNFL thickness measurements (p > 0.05). Conclusions Cirrus™ HD-OCT ONH parameters are able to discriminate between eyes that are normal from those with glaucoma or even mild glaucoma. There is no difference in the ability of ONH parameters and RNFL thickness measurement, as measured with Cirrus™ OCT, to distinguish between normal and glaucomatous eyes. PMID:20920824

Combined application of BDNF to the eye and brain enhances ganglion cell survival and function in the cat after optic nerve injury.

PubMed

Weber, Arthur J; Viswanáthan, Suresh; Ramanathan, Chidambaram; Harman, Christine D

2010-01-01

To determine whether application of BDNF to the eye and brain provides a greater level of neuroprotection after optic nerve injury than treatment of the eye alone. Retinal ganglion cell survival and pattern electroretinographic responses were compared in normal cat eyes and in eyes that received (1) a mild nerve crush and no treatment, (2) a single intravitreal injection of BDNF at the time of the nerve injury, or (3) intravitreal treatment combined with 1 to 2 weeks of continuous delivery of BDNF to the visual cortex, bilaterally. Relative to no treatment, administration of BDNF to the eye alone resulted in a significant increase in ganglion cell survival at both 1 and 2 weeks after nerve crush (1 week, 79% vs. 55%; 2 weeks, 60% vs. 31%). Combined treatment of the eye and visual cortex resulted in a modest additional increase (17%) in ganglion cell survival in the 1-week eyes, a further significant increase (55%) in the 2-week eyes, and ganglion cell survival levels for both that were comparable to normal (92%-93% survival). Pattern ERG responses for all the treated eyes were comparable to normal at 1 week after injury; however, at 2 weeks, only the responses of eyes receiving the combined BDNF treatment remained so. Although treatment of the eye alone with BDNF has a significant impact on ganglion cell survival after optic nerve injury, combined treatment of the eye and brain may represent an even more effective approach and should be considered in the development of future optic neuropathy-related neuroprotection strategies.

Undetected sex chromosome aneuploidy by chromosomal microarray.

PubMed

Markus-Bustani, Keren; Yaron, Yuval; Goldstein, Myriam; Orr-Urtreger, Avi; Ben-Shachar, Shay

2012-11-01

We report on a case of a female fetus found to be mosaic for Turner syndrome (45,X) and trisomy X (47,XXX). Chromosomal microarray analysis (CMA) failed to detect the aneuploidy because of a normal average dosage of the X chromosome. This case represents an unusual instance in which CMA may not detect chromosomal aberrations. Such a possibility should be taken into consideration in similar cases where CMA is used in a clinical setting. © 2012 John Wiley & Sons, Ltd.

Remodeling of the Connective Tissue Microarchitecture of the Lamina Cribrosa in Early Experimental Glaucoma

PubMed Central

Roberts, Michael D.; Grau, Vicente; Grimm, Jonathan; Reynaud, Juan; Bellezza, Anthony J.; Burgoyne, Claude F.; Downs, J. Crawford

2009-01-01

Purpose To characterize the trabeculated connective tissue microarchitecture of the lamina cribrosa (LC) in terms of total connective tissue volume (CTV), connective tissue volume fraction (CTVF), predominant beam orientation, and material anisotropy in monkeys with early experimental glaucoma (EG). Methods The optic nerve heads from three monkeys with unilateral EG and four bilaterally normal monkeys were three dimensionally reconstructed from tissues perfusion fixed at an intraocular pressure of 10 mm Hg. A three-dimensional segmentation algorithm was used to extract a binary, voxel-based representation of the porous LC connective tissue microstructure that was regionalized into 45 subvolumes, and the following quantities were calculated: total CTV within the LC, mean and regional CTVF, regional predominant beam orientation, and mean and regional material anisotropy. Results Regional variation within the laminar microstructure was considerable within the normal eyes of all monkeys. The laminar connective tissue was generally most dense in the central and superior regions for the paired normal eyes, and laminar beams were radially oriented at the periphery for all eyes considered. CTV increased substantially in EG eyes compared with contralateral normal eyes (82%, 44%, 45% increases; P < 0.05), but average CTVF changed little (−7%, 1%, and −2% in the EG eyes). There were more laminar beams through the thickness of the LC in the EG eyes than in the normal controls (46%, 18%, 17% increases). Conclusions The substantial increase in laminar CTV with little change in CTVF suggests that significant alterations in connective and nonconnective tissue components in the laminar region occur in the early stages of glaucomatous damage. PMID:18806292

The Stiles-Crawford Effect: spot-size ratio departure in retinitis pigmentosa

NASA Astrophysics Data System (ADS)

Sharma, Nachieketa K.; Lakshminarayanan, Vasudevan

2016-04-01

The Stiles-Crawford effect of the first kind is the retina's compensative response to loss of luminance efficiency for oblique stimulation manifested as the spot-size ratio departure from the perfect power coupling for a normal human eye. In a retinitis pigmentosa eye (RP), the normal cone photoreceptor morphology is affected due to foveal cone loss and disrupted cone mosaic spatial arrangement with reduction in directional sensitivity. We show that the flattened Stiles-Crawford function (SCF) in a RP eye is due to a different spot-size ratio departure profile, that is, for the same loss of luminance efficiency, a RP eye has a smaller departure from perfect power coupling compared to a normal eye. Again, the difference in spot-size ratio departure increases from the centre towards the periphery, having zero value for axial entry and maximum value for maximum peripheral entry indicating dispersal of photoreceptor alignment which prevents the retina to go for a bigger compensative response as it lacks both in number and appropriate cone morphology to tackle the loss of luminance efficiency for oblique stimulation. The slope of departure profile also testifies to the flattened SCF for a RP eye. Moreover, the discrepancy in spot-size ratio departure between a normal and a RP eye is shown to have a direct bearing on the Stiles-Crawford diminution of visibility.

Evaluation of point-of-care test for elevated tear matrix metalloproteinase 9 in post-LASIK dry eyes.

PubMed

Chan, Tommy C Y; Ye, Cong; Chan, Kwok Ping; Chu, Kai On; Jhanji, Vishal

2016-09-01

To evaluate the performance of a point-of-care test for detection of matrix metalloproteinase 9 (MMP-9) levels in post-laser-assisted in situ keratomileusis (LASIK) dry eyes. A comparative study between patients with mild to moderate post-LASIK dry eyes and age-matched normal subjects was conducted. Ocular surface disease index (OSDI), tear break-up time (TBUT), and tear film MMP-9 and total protein levels were compared between the two groups. A point-of-care test device (RPS InflammaDry, Sarasota, Florida, USA) was utilised to confirm elevated MMP-9 levels in tear film. Fourteen post-LASIK dry eyes and 34 normal eyes were included. There was no significant difference in age and gender between both groups (p>0.175). The OSDI was significantly higher (25.5±7.7 vs 7.4±2.5; p<0.001) and TBUT levels were significantly lower (5.4±0.9 vs 13.5±2.3; p<0.001) in patients with dry eye compared with normal subjects. The tear film MMP-9 levels were 52.7±32.5 ng/mL in dry eyes and 4.1±2.1 ng/mL in normal eyes (p<0.001). MMP-9 levels were >40 ng/mL in 7/14 (50.0%) post-LASIK dry eyes. The InflammaDry was positive in 8/14 (57.1%) post-LASIK eyes. All positive cases had tear film MMP-9 levels ≥38.03 ng/mL. Agreement between InflammaDry and MMP-9 was excellent with Cohen κ value of 0.857 in post-LASIK dry eyes. Only half of post-LASIK dry eyes were found to have significant inflammation associated with elevated MMP-9. The OSDI is useful to non-specifically identify patients with symptomatic dry eye while the InflammaDry determined which patients with dry eye were associated with significant inflammation that may guide therapeutic management decisions. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Infrared ocular thermography in dogs with and without keratoconjunctivitis sicca.

PubMed

Biondi, Flávia; Dornbusch, Peterson T; Sampaio, Manuella; Montiani-Ferreira, Fabiano

2015-01-01

Infrared thermography was used to measure temperature differences of the corneal surface between nasal and temporal limbus regions and central cornea of normal dogs and dogs with keratoconjunctivitis sicca (KCS), in order to establish temperature values in normal canine eyes and in patients with decreased Schirmer tear tests (STT) values. Dogs investigated were all either patients seen at the Veterinary Teaching Hospital of Federal University of Paraná or normal dogs that belonged to the same institution. STT were performed in all eyes. A total of 40 control eyes (STT ≥15 mm/min) and 20 eyes with low STT values (STT ≤14 mm/min) were examined. The mean STT value for eyes with normal STT values was 22.9 ± 3.9 mm/min (mean ± standard deviation), and the mean STT value for eyes with low STT value was 7.2 ± 4.8 mm/min. The mean corneal temperature was significantly lower in eyes with low STT values than in control eyes (P < 0.0001). The following significant correlations were found: (i) Schirmer and breakup time (BUT) (P = 0.0001, r = 0.5); (ii) STT values and corneal surface temperature (P = 0.001, r = 0.256); (iii) STT values and age (P = 0.0001, r = -0.448); (iv) age and corneal surface temperature (P = 0.0001, r = -0.281); and (v) BUT and corneal surface temperature (P = 0.0001, r = 0.36). Thermography is a method that can differentiate between eyes with normal and abnormal STT values. In the future, thermography might be incorporated as part of the ophthalmic examination and perhaps become a popular ancillary test for the diagnoses of ocular surface disorders. © 2013 American College of Veterinary Ophthalmologists.

MAPK Target Sites of Eyes Absent Are Not Required for Eye Development or Survival in Drosophila

PubMed Central

Jusiak, Barbara; Abulimiti, Abuduaini; Haelterman, Nele; Chen, Rui; Mardon, Graeme

2012-01-01

Eyes absent (Eya) is a highly conserved transcription cofactor and protein phosphatase that plays an essential role in eye development and survival in Drosophila. Ectopic eye induction assays using cDNA transgenes have suggested that mitogen activated protein kinase (MAPK) activates Eya by phosphorylating it on two consensus target sites, S402 and S407, and that this activation potentiates the ability of Eya to drive eye formation. However, this mechanism has never been tested in normal eye development. In the current study, we generated a series of genomic rescue transgenes to investigate how loss- and gain-of-function mutations at these two MAPK target sites within Eya affect Drosophila survival and normal eye formation: eya+GR, the wild-type control; eyaSAGR, which lacks phosphorylation at the two target residues; and eyaSDEGR, which contains phosphomimetic amino acids at the same two residues. Contrary to the previous studies in ectopic eye development, all eya genomic transgenes tested rescue both eye formation and survival equally effectively. We conclude that, in contrast to ectopic eye formation, MAPK-mediated phosphorylation of Eya on S402 and S407 does not play a role in normal development. This is the first study in Drosophila to evaluate the difference in outcomes between genomic rescue and ectopic cDNA-based overexpression of the same gene. These findings indicate similar genomic rescue strategies may prove useful for re-evaluating other long-standing Drosophila developmental models. PMID:23251383

Effect of high pressurization versus normal pressurization on changes in intraocular pressure immediately after clear corneal cataract surgery.

PubMed

Hayashi, Ken; Yoshida, Motoaki; Manabe, Shin-Ichi; Yoshimura, Koichi

2014-01-01

To compare changes in intraocular pressure (IOP) immediately after clear corneal incision (CCI) cataract surgery between eyes in which IOP was adjusted to a high or normal range at the conclusion of surgery. Hayashi Eye Hospital, Fukuoka, Japan. Comparative case series. Either eye of patients scheduled for phacoemulsification was randomized to 1 of 2 groups as follows: eyes that were to be adjusted to (1) high IOP (22 to 40 mm Hg) or (2) normal IOP (10 to 21 mm Hg). The IOP was measured using a rebound tonometer preoperatively; at the conclusion of surgery; and 15, 30, 60, 120, and 180 minutes and 24 hours postoperatively. The Seidel test and anterior segment optical coherence tomography (AS-OCT) were performed. The mean IOP at the conclusion of surgery was 31.3 mm Hg in the high IOP group and 17.1 mm Hg in the normal IOP group. The IOP decreased to approximately 15 mm Hg by 15 minutes and did not change until 60 minutes in either group. The mean IOP did not differ significantly between groups throughout the observation period (P ≥.0634). Hypotony of 5 mm Hg or less was not detected in any eye. The Seidel test was negative and based on AS-OCT, the wound was closed at 60 minutes in all eyes. After adjusting IOP to a high or normal range, the IOP normalized within 15 minutes postoperatively and was stable for 24 hours. The wound was closed within 60 minutes postoperatively. Copyright © 2013 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

Measurement of central corneal thickness with optical low-coherence reflectometry and ultrasound pachymetry in normal and post-femtosecond laser in situ keratomileusis eyes.

PubMed

Huang, Jinhai; Liao, Na; Savini, Giacomo; Li, Yuanguang; Bao, Fangjun; Yu, Ye; Yu, Ayong; Wang, Qinmei

2015-02-01

To determine the repeatability and reproducibility of measurements of central corneal thickness (CCT) using optical low-coherence reflectometry (Lenstar LS900; Haag Streit) in normal eyes and post-femtosecond laser in situ keratomileusis (post-FS-LASIK) eyes and evaluate their agreement with ultrasound (US) pachymetry. CCT was measured using Lenstar and US pachymetry sequentially in normal and post-FS-LASIK eyes by 2 experienced observers. Intraoperator repeatability and interoperator reproducibility were assessed by within-subject standard deviation, test-retest repeatability, coefficient of variation (CoV), and intraclass correlation coefficient. Paired t-tests and Bland-Altman plots were used for analyzing agreement between the 2 devices. In this study, 55 healthy subjects and 50 post-FS-LASIK patients were recruited. Test-retest repeatability of Lenstar was within 10 μm, CoV was less than 1.0%, and intraclass correlation coefficient was more than 0.9 in both normal and post-FS-LASIK groups. Mean difference between these methods was 1.4 ± 4.2 μm and -1.7 ± 5.4 μm, respectively. Moreover, measurements of CCT showed narrow 95% limits of agreement (range, normal group: -6.8 and 9.6 μm; post-FS-LASIK group: -12.4 and 8.9 μm), which implied good agreement. Measurements of CCT using Lenstar showed excellent intraoperator repeatability and interoperator reproducibility both in normal eyes and post-FS-LASIK eyes. Measurements of CCT using Lenstar and US pachymetry showed good agreement and both can be used interchangeably.

Evaluation of retinal nerve fiber layer thickness in the area of apparently normal hemifield in glaucomatous eyes with optical coherence tomography.

PubMed

Kee, Changwon; Cho, Changhwan

2003-06-01

The authors investigated the correlation between visual field defects detected by automated perimetry and the thickness of the retinal nerve fiber layer measured with optical coherence tomography, and examined whether there is a decrease in retinal nerve fiber layer thickness in the apparently normal hemifield of glaucomatous eyes. Forty-one patients with glaucoma and 41 normal control subjects were included in this study. Statistical correlations between the sum of the total deviation of 37 stimuli of each hemifield and the ratio of decrease in retinal nerve fiber layer thickness were evaluated. The statistical difference between the retinal nerve fiber layer thickness of the apparently normal hemifield in glaucomatous eyes and that of the corresponding hemifield in normal subjects was also evaluated. There was a statistically significant correlation in the sum of the total deviation and retinal nerve fiber layer thickness decrease ratio (superior hemifield, P = 0.001; inferior hemifield, P = 0.003). There was no significant decrease in retinal nerve fiber layer thickness in the area that corresponded to the normal visual field in the hemifield defect with respect to the horizontal meridian in glaucomatous eyes (superior side, P = 0.148; inferior side, P = 0.341). Optical coherence tomography was capable of demonstrating and measuring retinal nerve fiber layer abnormalities. No changes in the retinal nerve fiber layer thickness of the apparently normal hemifield were observed in glaucomatous eyes.

A simple implementation of a normal mixture approach to differential gene expression in multiclass microarrays.

PubMed

McLachlan, G J; Bean, R W; Jones, L Ben-Tovim

2006-07-01

An important problem in microarray experiments is the detection of genes that are differentially expressed in a given number of classes. We provide a straightforward and easily implemented method for estimating the posterior probability that an individual gene is null. The problem can be expressed in a two-component mixture framework, using an empirical Bayes approach. Current methods of implementing this approach either have some limitations due to the minimal assumptions made or with more specific assumptions are computationally intensive. By converting to a z-score the value of the test statistic used to test the significance of each gene, we propose a simple two-component normal mixture that models adequately the distribution of this score. The usefulness of our approach is demonstrated on three real datasets.

Anteroposterior Patterning of Gene Expression in the Human Infant Sclera: Chondrogenic Potential and Wnt Signaling.

PubMed

Seko, Yuko; Azuma, Noriyuki; Yokoi, Tadashi; Kami, Daisuke; Ishii, Ryuga; Nishina, Sachiko; Toyoda, Masashi; Shimokawa, Hitoyata; Umezawa, Akihiro

2017-01-01

Purpose/Aim: We sought to identify the anteroposterior spatial gene expression hierarchy in the human sclera to develop a hypothesis for axial elongation and deformity of the eyeball. We analyzed the global gene expression of human scleral cells derived from distinct parts of the human infant sclera obtained from surgically enucleated eyes with retinoblastoma, using Affymetrix GeneChip oligonucleotide arrays, and compared, in particular, gene expression levels between the anterior and posterior parts of the sclera. The ages of three donors were 10M, 4M, and 1Y9M. K-means clustering analysis of gene expression revealed that expression levels of cartilage-associated genes such as COLXIA and ACAN increased from the anterior to the posterior part of the sclera. Microarray analyses and RT-PCR data showed that the expression levels of MGP, COLXIA, BMP4, and RARB were significantly higher in the posterior than in the anterior sclera of two independent infant eyes. Conversely, expression levels of WNT2, DKK2, GREM1, and HOXB2 were significantly higher in the anterior sclera. Among several Wnt-family genes examined, WNT2B was found to be expressed at a significantly higher level in the posterior sclera, and the reverse order was observed for WNT2. The results of luciferase reporter assays suggested that a GSK-3β inhibitor stimulated Wnt/β-catenin signaling particularly strongly in the posterior sclera. The expression pattern of RARB, a myopia-related gene, was similar in three independent eyes. Chondrogenic potential was higher and Wnt/β-catenin signaling was more potently activated by a GSK-3β inhibitor in the posterior than in the anterior part of the human infant sclera. Although the differences in the gene expression profiles between the anterior and posterior sclera might be involved only in normal growth processes, this anteroposterior hierarchy in the sclera might contribute to disorders involving abnormal elongation and deformity of the eyeball, including myopia.

Assessment of visual disability using visual evoked potentials.

PubMed

Jeon, Jihoon; Oh, Seiyul; Kyung, Sungeun

2012-08-06

The purpose of this study is to validate the use of visual evoked potential (VEP) to objectively quantify visual acuity in normal and amblyopic patients, and determine if it is possible to predict visual acuity in disability assessment to register visual pathway lesions. A retrospective chart review was conducted of patients diagnosed with normal vision, unilateral amblyopia, optic neuritis, and visual disability who visited the university medical center for registration from March 2007 to October 2009. The study included 20 normal subjects (20 right eyes: 10 females, 10 males, ages 9-42 years), 18 unilateral amblyopic patients (18 amblyopic eyes, ages 19-36 years), 19 optic neuritis patients (19 eyes: ages 9-71 years), and 10 patients with visual disability having visual pathway lesions. Amplitude and latencies were analyzed and correlations with visual acuity (logMAR) were derived from 20 normal and 18 amblyopic subjects. Correlation of VEP amplitude and visual acuity (logMAR) of 19 optic neuritis patients confirmed relationships between visual acuity and amplitude. We calculated the objective visual acuity (logMAR) of 16 eyes from 10 patients to diagnose the presence or absence of visual disability using relations derived from 20 normal and 18 amblyopic eyes. Linear regression analyses between amplitude of pattern visual evoked potentials and visual acuity (logMAR) of 38 eyes from normal (right eyes) and amblyopic (amblyopic eyes) subjects were significant [y = -0.072x + 1.22, x: VEP amplitude, y: visual acuity (logMAR)]. There were no significant differences between visual acuity prediction values, which substituted amplitude values of 19 eyes with optic neuritis into function. We calculated the objective visual acuity of 16 eyes of 10 patients to diagnose the presence or absence of visual disability using relations of y = -0.072x + 1.22 (-0.072). This resulted in a prediction reference of visual acuity associated with malingering vs. real disability in a range >5.77 μV. The results could be useful, especially in cases of no obvious pale disc with trauma. Visual acuity quantification using absolute value of amplitude in pattern visual evoked potentials was useful in confirming subjective visual acuity for cutoff values >5.77 μV in disability evaluation to discriminate the malingering from real disability.

Assessment of visual disability using visual evoked potentials

PubMed Central

2012-01-01

Background The purpose of this study is to validate the use of visual evoked potential (VEP) to objectively quantify visual acuity in normal and amblyopic patients, and determine if it is possible to predict visual acuity in disability assessment to register visual pathway lesions. Methods A retrospective chart review was conducted of patients diagnosed with normal vision, unilateral amblyopia, optic neuritis, and visual disability who visited the university medical center for registration from March 2007 to October 2009. The study included 20 normal subjects (20 right eyes: 10 females, 10 males, ages 9–42 years), 18 unilateral amblyopic patients (18 amblyopic eyes, ages 19–36 years), 19 optic neuritis patients (19 eyes: ages 9–71 years), and 10 patients with visual disability having visual pathway lesions. Amplitude and latencies were analyzed and correlations with visual acuity (logMAR) were derived from 20 normal and 18 amblyopic subjects. Correlation of VEP amplitude and visual acuity (logMAR) of 19 optic neuritis patients confirmed relationships between visual acuity and amplitude. We calculated the objective visual acuity (logMAR) of 16 eyes from 10 patients to diagnose the presence or absence of visual disability using relations derived from 20 normal and 18 amblyopic eyes. Results Linear regression analyses between amplitude of pattern visual evoked potentials and visual acuity (logMAR) of 38 eyes from normal (right eyes) and amblyopic (amblyopic eyes) subjects were significant [y = −0.072x + 1.22, x: VEP amplitude, y: visual acuity (logMAR)]. There were no significant differences between visual acuity prediction values, which substituted amplitude values of 19 eyes with optic neuritis into function. We calculated the objective visual acuity of 16 eyes of 10 patients to diagnose the presence or absence of visual disability using relations of y = −0.072x + 1.22 (−0.072). This resulted in a prediction reference of visual acuity associated with malingering vs. real disability in a range >5.77 μV. The results could be useful, especially in cases of no obvious pale disc with trauma. Conclusions Visual acuity quantification using absolute value of amplitude in pattern visual evoked potentials was useful in confirming subjective visual acuity for cutoff values >5.77 μV in disability evaluation to discriminate the malingering from real disability. PMID:22866948

Three-Dimensional Eye Tracking in a Surgical Scenario.

PubMed

Bogdanova, Rositsa; Boulanger, Pierre; Zheng, Bin

2015-10-01

Eye tracking has been widely used in studying the eye behavior of surgeons in the past decade. Most eye-tracking data are reported in a 2-dimensional (2D) fashion, and data for describing surgeons' behaviors on stereoperception are often missed. With the introduction of stereoscopes in laparoscopic procedures, there is an increasing need for studying the depth perception of surgeons under 3D image-guided surgery. We developed a new algorithm for the computation of convergence points in stereovision by measuring surgeons' interpupillary distance, the distance to the view target, and the difference between gaze locations of the 2 eyes. To test the feasibility of our new algorithm, we recruited 10 individuals to watch stereograms using binocular disparity and asked them to develop stereoperception using a cross-eyed viewing technique. Participants' eye motions were recorded by the Tobii eye tracker while they performed the trials. Convergence points between normal and stereo-viewing conditions were computed using the developed algorithm. All 10 participants were able to develop stereovision after a short period of training. During stereovision, participants' eye convergence points were 14 ± 1 cm in front of their eyes, which was significantly closer than the convergence points under the normal viewing condition (77 ± 20 cm). By applying our method of calculating convergence points using eye tracking, we were able to elicit the eye movement patterns of human operators between the normal and stereovision conditions. Knowledge from this study can be applied to the design of surgical visual systems, with the goal of improving surgical performance and patient safety. © The Author(s) 2015.

Supervised normalization of microarrays

PubMed Central

Mecham, Brigham H.; Nelson, Peter S.; Storey, John D.

2010-01-01

Motivation: A major challenge in utilizing microarray technologies to measure nucleic acid abundances is ‘normalization’, the goal of which is to separate biologically meaningful signal from other confounding sources of signal, often due to unavoidable technical factors. It is intuitively clear that true biological signal and confounding factors need to be simultaneously considered when performing normalization. However, the most popular normalization approaches do not utilize what is known about the study, both in terms of the biological variables of interest and the known technical factors in the study, such as batch or array processing date. Results: We show here that failing to include all study-specific biological and technical variables when performing normalization leads to biased downstream analyses. We propose a general normalization framework that fits a study-specific model employing every known variable that is relevant to the expression study. The proposed method is generally applicable to the full range of existing probe designs, as well as to both single-channel and dual-channel arrays. We show through real and simulated examples that the method has favorable operating characteristics in comparison to some of the most highly used normalization methods. Availability: An R package called snm implementing the methodology will be made available from Bioconductor (http://bioconductor.org). Contact: jstorey@princeton.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:20363728

Eye-specific retinogeniculate segregation proceeds normally following disruption of patterned spontaneous retinal activity.

PubMed

Speer, Colenso M; Sun, Chao; Liets, Lauren C; Stafford, Ben K; Chapman, Barbara; Cheng, Hwai-Jong

2014-11-07

Spontaneous retinal activity (SRA) is important during eye-specific segregation within the dorsal lateral geniculate nucleus (dLGN), but the feature(s) of activity critical for retinogeniculate refinement are controversial. Pharmacologically or genetically manipulating cholinergic signaling during SRA perturbs correlated retinal ganglion cell (RGC) spiking and disrupts eye-specific retinofugal refinement in vivo, consistent with an instructive role for SRA during visual system development. Paradoxically, ablating the starburst amacrine cells (SACs) that generate cholinergic spontaneous activity disrupts correlated RGC firing without impacting retinal activity levels or eye-specific segregation in the dLGN. Such experiments suggest that patterned SRA during retinal waves is not critical for eye-specific refinement and instead, normal activity levels are permissive for retinogeniculate development. Here we revisit the effects of ablating the cholinergic network during eye-specific segregation and show that SAC ablation disrupts, but does not eliminate, retinal waves with no concomitant impact on normal eye-specific segregation in the dLGN. We induced SAC ablation in postnatal ferret pups beginning at birth by intraocular injection of a novel immunotoxin selective for the ferret vesicular acetylcholine transporter (Ferret VAChT-Sap). Through dual-patch whole-cell and multi-electrode array recording we found that SAC ablation altered SRA patterns and led to significantly smaller retinal waves compared with controls. Despite these defects, eye-specific segregation was normal. Further, interocular competition for target territory in the dLGN proceeded in cases where SAC ablation was asymmetric in the two eyes. Our data demonstrate normal eye-specific retinogeniculate development despite significant abnormalities in patterned SRA. Comparing our current results with earlier studies suggests that defects in retinal wave size, absolute levels of SRA, correlations between RGC pairs, RGC burst frequency, high frequency RGC firing during bursts, and the number of spikes per RGC burst are each uncorrelated with abnormalities in eye-specific segregation in the dLGN. An increase in the fraction of asynchronous spikes occurring outside of bursts and waves correlates with eye-specific segregation defects in studies reported to date. These findings highlight the relative importance of different features of SRA while providing additional constraints for computational models of Hebbian plasticity mechanisms in the developing visual system.

Rotating Scheimpflug Imaging Indices in Different Grades of Keratoconus

PubMed Central

2016-01-01

Purpose. To evaluate accuracy of various Keratoconus (KC) screening indices, in relation to Topographic Keratoconus (TKC) grading. Setting. Al Watany Eye Hospital, Cairo, Egypt. Methods. Data of 103 normal (group 1) and 73 KC eyes (group 2), imaged by Pentacam (branded as Allegro Oculyzer), were analysed. Group 2 was divided into 2a: 14 eyes (TKC = 1, early KC), 2b: 25 eyes (TKC = 1 to 2 or 2, moderate KC), and 2c: 34 eyes (TKC = 2 to 3 up to 4, severe KC). Participants were followed up for six years to confirm diagnosis. Area under the receiver operating characteristic curve (AUROC) was calculated for evaluated curvature, elevation, and pachymetry indices with various reference shapes at different diameters. Results. When comparing normal to KC eyes, ten indices had significantly higher AUROC. Only five of them had significantly higher AUROC in early KC compared to normal corneas: Pachymetry Progression Index- (PPI-) Maximum (Max), Ambrósio's Relational Thickness- (ART-) Max, PPI-Max minus PPI-Minimum (Min), central corneal thickness (CCT), and diagonal decentration of thinnest point from the apex (AUROC = 0.690, 0.690, 0.687, 0.683, and 0.674, resp.). Conclusion. Generally, ten pachymetry and elevation-based indices had significantly higher AUROC. Five indices had statistically significant high AUROC when comparing early KC to normal corneas. PMID:27579178

Differences in intermittent postural control between normal-weight and obese children.

PubMed

Villarrasa-Sapiña, Israel; García-Massó, Xavier; Serra-Añó, Pilar; Garcia-Lucerga, Consolación; Gonzalez, Luis-Millán; Lurbe, Empar

2016-09-01

The main objective of this study was to determine differences in postural control between obese and non-obese children. The study design was cross-sectional, prospective, between-subjects. Postural control variables were obtained from a group of obese children and a normal-weight control group under two different postural conditions: bipedal standing position with eyes open and bipedal standing with eyes closed. Variables were obtained for each balance condition using time domain and sway-density plot analysis of the center of pressure signals acquired by means of a force plate. Pairwise comparisons revealed significant differences between obese and normal-weight children in mean velocity in antero-posterior and medio-lateral directions, ellipse area and mean distance with both eyes open and eyes closed. Normal-weight subjects obtained lower values in all these variables than obese subjects. Furthermore, there were differences between both groups in mean peaks with eyes open and in mean time with eyes closed. Alterations were detected in the intermittent postural control in obese children. According to the results obtained, active anticipatory control produces higher center of pressure displacement responses in obese children and the periods during which balance is maintained by passive control and reflex mechanisms are of shorter duration. Copyright © 2016 Elsevier B.V. All rights reserved.

Construction of a robust microarray from a non-model species (largemouth bass) using pyrosequencing technology

PubMed Central

Garcia-Reyero, Natàlia; Griffitt, Robert J.; Liu, Li; Kroll, Kevin J.; Farmerie, William G.; Barber, David S.; Denslow, Nancy D.

2009-01-01

A novel custom microarray for largemouth bass (Micropterus salmoides) was designed with sequences obtained from a normalized cDNA library using the 454 Life Sciences GS-20 pyrosequencer. This approach yielded in excess of 58 million bases of high-quality sequence. The sequence information was combined with 2,616 reads obtained by traditional suppressive subtractive hybridizations to derive a total of 31,391 unique sequences. Annotation and coding sequences were predicted for these transcripts where possible. 16,350 annotated transcripts were selected as target sequences for the design of the custom largemouth bass oligonucleotide microarray. The microarray was validated by examining the transcriptomic response in male largemouth bass exposed to 17β-œstradiol. Transcriptomic responses were assessed in liver and gonad, and indicated gene expression profiles typical of exposure to œstradiol. The results demonstrate the potential to rapidly create the tools necessary to assess large scale transcriptional responses in non-model species, paving the way for expanded impact of toxicogenomics in ecotoxicology. PMID:19936325

Cross-platform normalization of microarray and RNA-seq data for machine learning applications

PubMed Central

Thompson, Jeffrey A.; Tan, Jie

2016-01-01

Large, publicly available gene expression datasets are often analyzed with the aid of machine learning algorithms. Although RNA-seq is increasingly the technology of choice, a wealth of expression data already exist in the form of microarray data. If machine learning models built from legacy data can be applied to RNA-seq data, larger, more diverse training datasets can be created and validation can be performed on newly generated data. We developed Training Distribution Matching (TDM), which transforms RNA-seq data for use with models constructed from legacy platforms. We evaluated TDM, as well as quantile normalization, nonparanormal transformation, and a simple log2 transformation, on both simulated and biological datasets of gene expression. Our evaluation included both supervised and unsupervised machine learning approaches. We found that TDM exhibited consistently strong performance across settings and that quantile normalization also performed well in many circumstances. We also provide a TDM package for the R programming language. PMID:26844019

Knowledge and attitude of guardians towards eye health of primary school pupils in Ilorin, Nigeria.

PubMed

Ayanniyi, A A; Olatunji, F O; Mahmoud, A O; Ayanniyi, R O

2010-03-01

To determine guardians' knowledge and attitude towards pupils' eye health and draw implication for designing children-oriented ocular health messages. A survey of 1,393 guardians selected through multistage random sampling in Ilorin, Nigeria. Using structured questionnaire, information sought included guardians' demographic characteristics, relationship to pupils, occupation, awareness of eye specialists, perception of normal vision, pupils' eye complaints, and ways of treating children eye conditions. Data analysis was done with SPSS 12.0.1. The test of significance was performed using Chi square test and significance was taken at p < 0.05. Guardians comprised 689 (49.4%) males and 704 (50.6%) females, mean age 43.61 SD 11.45. Most (88.54%) were pupils' parents and (11.46%) were relations (n=1,318); (55.15%) were in low-paying occupations (n=1,311); (87.92%) were aware of eye specialists, (12.08%) unaware, (n=1192); (97.27%) adjudged normal vision at least important, (2.73%) not important (n=1,174). Pupils' eye complaints (n=914) included pain (26.04%), itching (24.73%), redness (21.12%), discharge (8.53%), blur vision (8.21%), photophobia (7.33%) and lacrimation (4.05%). Guardians (n=1,069) managed pupils' eye diseases using hospital treatment (61.65%), neglect (21.33%), self medication (9.26%) and traditional medication (7.76%). There were no significant associations between guardians' ways of managing pupils' eye diseases and their views on normal vision (p = 0.940); awareness of eye care specialists (p = 0.952); and economic occupational grouping (p = 0.959). The negative implications of neglecting eye diseases and use of self and harmful traditional eye-medications by some of the guardians need to be discouraged by appropriate eye health education.

A microarray analysis of retinal transcripts that are controlled by image contrast in mice

PubMed Central

Brand, Christine; Schaeffel, Frank

2007-01-01

Purpose The development of myopia is controlled by still largely unknown retinal signals. The aim of this study was to investigate the changes in retinal mRNA expression after different periods of visual deprivation in mice, while controlling for retinal illuminance. Methods Each group consisted of three male C57BL/6 mice. Treatment periods were 30 min, 4 h, and 6+6 h. High spatial frequencies were filtered from the retinal image by frosted diffusers over one eye while the fellow eyes were covered by clear neutral density (ND) filters that exhibited similar light attenuating properties (0.1 log units) as the diffusers. For the final 30 min of the respective treatment period mice were individually placed in a clear Perspex cylinder that was positioned in the center of a rotating (60 degrees) large drum. The inside of the drum was covered with a 0.1 cyc/degree vertical square wave grating. This visual environment was chosen to standardize illuminances and contrasts seen by the mice. Labeled cRNA was prepared and hybridized to Affymetrix GeneChip® Mouse Genome 430 2.0 arrays. Alterations in mRNA expression levels of candidate genes with potential biological relevance were confirmed by semi-quantitative real-time reverse transcription polymerase chain reaction (RT-PCR). Results In all groups, Egr-1 mRNA expression was reduced in diffuser-treated eyes. Furthermore, the degradation of the spatial frequency spectrum also changed the cFos mRNA level, with reduced expression after 4 h of diffuser treatment. Other interesting candidates were Akt2, which was up-regulated after 30 min of deprivation and Mapk8ip3, a neuron specific JNK binding and scaffolding protein that was temporally regulated in the diffuser-treated eyes only. Conclusions The microarray analysis demonstrated a pattern of differential transcriptional changes, even though differences in the retinal images were restricted to spatial features. The candidate genes may provide further insight into the biochemical short-term changes following retinal image degradation in mice. Because deprivation of spatial vision leads to increased eye growth and myopia in both animals and humans, it is believed some of the identified genes play a role in myopia development. PMID:17653032

Iris autofluorescence in Fuchs' heterochromic uveitis.

PubMed

Liu, Qian; Jia, Yading; Zhang, Suhua; Xie, Juan; Chang, Xin; Hou, Jia; Li, Gaiyun; Koch, Douglas D; Wang, Li

2016-10-01

To explore the characteristic autofluorescence patterns of iris depigmentation in eyes diagnosed with Fuchs' heterochromic uveitis (FHU). Near-infrared autofluorescence images and colour images of iris were taken in 21 eyes of 21 patients with FHU, 30 eyes of 15 normal subjects, 30 eyes of 15 normal age-related iris atrophy and 33 eyes of 20 patients with uveitis other than FHU. The confocal scanning laser ophthalmoscope (Heidelberg Retina Angiograph 2, HRA2) was used for melanin-related autofluorescence imaging. The indocyanine green angiography mode of HRA2 was applied for near-infrared laser imaging, and the wavelength of the excitation laser was 795 nm. Iris colour images were also taken with the slit lamp. In normal iris, moderately intense autofluorescence was noted for the pigment ruff at the pupillary border, the crests in the pupillary zone and the collarette; and there was mild autofluorescence in the ciliary zone. In eyes with age-related iris atrophy and uveitis, much less autofluorescence was seen than the healthy normal irides. In eyes with FHU, there was moderate but discontinuous autofluorescence in the pigment ruff, a petaloid pattern of autofluorescence in the pupillary zone, moderate autofluorescence in the collarette and reticular pattern of autofluorescence in the ciliary zone. Characteristic autofluorescence patterns appeared in eyes diagnosed with FHU. Near-infrared autofluorescence is a promising objective technique to document the iris changes in FHU. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Correcting highly aberrated eyes using large-stroke adaptive optics.

PubMed

Sabesan, Ramkumar; Ahmad, Kamran; Yoon, Geunyoung

2007-11-01

To investigate the optical performance of a large-stroke deformable mirror in correcting large aberrations in highly aberrated eyes. A large-stroke deformable mirror (Mirao 52D; Imagine Eyes) and a Shack-Hartmann wavefront sensor were used in an adaptive optics system. Closed-loop correction of the static aberrations of a phase plate designed for an advanced keratoconic eye was performed for a 6-mm pupil. The same adaptive optics system was also used to correct the aberrations in one eye each of two moderate keratoconic and three normal human eyes for a 6-mm pupil. With closed-loop correction of the phase plate, the total root-mean-square (RMS) over a 6-mm pupil was reduced from 3.54 to 0.04 microm in 30 to 40 iterations, corresponding to 3 to 4 seconds. Adaptive optics closed-loop correction reduced an average total RMS of 1.73+/-0.998 to 0.10+/-0.017 microm (higher order RMS of 0.39+/-0.124 to 0.06+/-0.004 microm) in the three normal eyes and 2.73+/-1.754 to 0.10+/-0.001 microm (higher order RMS of 1.82+/-1.058 to 0.05+/-0.017 microm) in the two keratoconic eyes. Aberrations in both normal and highly aberrated eyes were successfully corrected using the large-stroke deformable mirror to provide almost perfect optical quality. This mirror can be a powerful tool to assess the limit of visual performance achievable after correcting the aberrations, especially in eyes with abnormal corneal profiles.

Functional visual acuity in patients with successfully treated amblyopia: a pilot study.

PubMed

Hoshi, Sujin; Hiraoka, Takahiro; Kotsuka, Junko; Sato, Yumiko; Izumida, Shinya; Kato, Atsuko; Ueno, Yuta; Fukuda, Shinichi; Oshika, Tetsuro

2017-06-01

The aim of this study was to use conventional visual acuity measurements to quantify the functional visual acuity (FVA) in eyes with successfully treated amblyopia, and to compare the findings with those for contralateral normal eyes. Nineteen patients (7 boys, 12 girls; age 7.5 ± 2.2 years) with successfully treated unilateral amblyopia and the same conventional decimal visual acuity in both eyes (better than 1.0) were enrolled. FVA, the visual maintenance ratio (VMR), maximum and minimum visual acuity, and the average response time were recorded for both eyes of all patients using an FVA measurement system. The differences in FVA values between eyes were analyzed. The mean LogMAR FVA scores, VMR (p < 0.001 for both), and the LogMAR maximum (p < 0.005) and minimum visual acuity (p < 0.001) were significantly poorer for the eyes with treated amblyopia than for the contralateral normal eyes. There was no significant difference in the average response time. Our results indicate that FVA and VMR were poorer for eyes with treated amblyopia than for normal eyes, even though the treatment for amblyopia was considered successful on the basis of conventional visual acuity measurements. These results suggest that visual function is impaired in eyes with amblyopia, regardless of treatment success, and that FVA measurements can provide highly valuable diagnosis and treatment information that is not readily provided by conventional visual acuity measurements.

Genomic profiling of neutrophil transcripts in Asian Qigong practitioners: a pilot study in gene regulation by mind-body interaction.

PubMed

Li, Quan-Zhen; Li, Ping; Garcia, Gabriela E; Johnson, Richard J; Feng, Lili

2005-02-01

The great similarity of the genomes of humans and other species stimulated us to search for genes regulated by elements associated with human uniqueness, such as the mind-body interaction. DNA microarray technology offers the advantage of analyzing thousands of genes simultaneously, with the potential to determine healthy phenotypic changes in gene expression. The aim of this study was to determine the genomic profile and function of neutrophils in Falun Gong (FLG, an ancient Chinese Qigong) practitioners, with healthy subjects as controls. Six (6) Asian FLG practitioners and 6 Asian normal healthy controls were recruited for our study. The practitioners have practiced FLG for at least 1 year (range, 1-5 years). The practice includes daily reading of FLG books and daily practice of exercises lasting 1-2 hours. Selected normal healthy controls did not perform Qigong, yoga, t'ai chi, or any other type of mind-body practice, and had not followed any conventional physical exercise program for at least 1 year. Neutrophils were isolated from fresh blood and assayed for gene expression, using microarrays and RNase protection assay (RPA), as well as for function (phagocytosis) and survival (apoptosis). The changes in gene expression of FLG practitioners in contrast to normal healthy controls were characterized by enhanced immunity, downregulation of cellular metabolism, and alteration of apoptotic genes in favor of a rapid resolution of inflammation. The lifespan of normal neutrophils was prolonged, while the inflammatory neutrophils displayed accelerated cell death in FLG practitioners as determined by enzyme-linked immunosorbent assay. Correlating with enhanced immunity reflected by microarray data, neutrophil phagocytosis was significantly increased in Qigong practitioners. Some of the altered genes observed by microarray were confirmed by RPA. Qigong practice may regulate immunity, metabolic rate, and cell death, possibly at the transcriptional level. Our pilot study provides the first evidence that Qigong practice may exert transcriptional regulation at a genomic level. New approaches are needed to study how genes are regulated by elements associated with human uniqueness, such as consciousness, cognition, and spirituality.

Gene Expression Profiling of Gastric Cancer

PubMed Central

Marimuthu, Arivusudar; Jacob, Harrys K.C.; Jakharia, Aniruddha; Subbannayya, Yashwanth; Keerthikumar, Shivakumar; Kashyap, Manoj Kumar; Goel, Renu; Balakrishnan, Lavanya; Dwivedi, Sutopa; Pathare, Swapnali; Dikshit, Jyoti Bajpai; Maharudraiah, Jagadeesha; Singh, Sujay; Sameer Kumar, Ghantasala S; Vijayakumar, M.; Veerendra Kumar, Kariyanakatte Veeraiah; Premalatha, Chennagiri Shrinivasamurthy; Tata, Pramila; Hariharan, Ramesh; Roa, Juan Carlos; Prasad, T.S.K; Chaerkady, Raghothama; Kumar, Rekha Vijay; Pandey, Akhilesh

2015-01-01

Gastric cancer is the second leading cause of cancer death worldwide, both in men and women. A genomewide gene expression analysis was carried out to identify differentially expressed genes in gastric adenocarcinoma tissues as compared to adjacent normal tissues. We used Agilent’s whole human genome oligonucleotide microarray platform representing ~41,000 genes to carry out gene expression analysis. Two-color microarray analysis was employed to directly compare the expression of genes between tumor and normal tissues. Through this approach, we identified several previously known candidate genes along with a number of novel candidate genes in gastric cancer. Testican-1 (SPOCK1) was one of the novel molecules that was 10-fold upregulated in tumors. Using tissue microarrays, we validated the expression of testican-1 by immunohistochemical staining. It was overexpressed in 56% (160/282) of the cases tested. Pathway analysis led to the identification of several networks in which SPOCK1 was among the topmost networks of interacting genes. By gene enrichment analysis, we identified several genes involved in cell adhesion and cell proliferation to be significantly upregulated while those corresponding to metabolic pathways were significantly downregulated. The differentially expressed genes identified in this study are candidate biomarkers for gastric adenoacarcinoma. PMID:27030788

Comparing the Effects of Particulate Matter on the Ocular Surfaces of Normal Eyes and a Dry Eye Rat Model.

PubMed

Han, Ji Yun; Kang, Boram; Eom, Youngsub; Kim, Hyo Myung; Song, Jong Suk

2017-05-01

To compare the effect of exposure to particulate matter on the ocular surface of normal and experimental dry eye (EDE) rat models. Titanium dioxide (TiO2) nanoparticles were used as the particulate matter. Rats were divided into 4 groups: normal control group, TiO2 challenge group of the normal model, EDE control group, and TiO2 challenge group of the EDE model. After 24 hours, corneal clarity was compared and tear samples were collected for quantification of lactate dehydrogenase, MUC5AC, and tumor necrosis factor-α concentrations. The periorbital tissues were used to evaluate the inflammatory cell infiltration and detect apoptotic cells. The corneal clarity score was greater in the EDE model than in the normal model. The score increased after TiO2 challenge in each group compared with each control group (normal control vs. TiO2 challenge group, 0.0 ± 0.0 vs. 0.8 ± 0.6, P = 0.024; EDE control vs. TiO2 challenge group, 2.2 ± 0.6 vs. 3.8 ± 0.4, P = 0.026). The tear lactate dehydrogenase level and inflammatory cell infiltration on the ocular surface were higher in the EDE model than in the normal model. These measurements increased significantly in both normal and EDE models after TiO2 challenge. The tumor necrosis factor-α levels and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling-positive cells were also higher in the EDE model than in the normal model. TiO2 nanoparticle exposure on the ocular surface had a more prominent effect in the EDE model than it did in the normal model. The ocular surface of dry eyes seems to be more vulnerable to fine dust of air pollution than that of normal eyes.

Hypodense regions (holes) in the retinal nerve fiber layer in frequency-domain OCT scans of glaucoma patients and suspects.

PubMed

Xin, Daiyan; Talamini, Christine L; Raza, Ali S; de Moraes, Carlos Gustavo V; Greenstein, Vivienne C; Liebmann, Jeffrey M; Ritch, Robert; Hood, Donald C

2011-09-09

To better understand hypodense regions (holes) that appear in the retinal nerve fiber layer (RNFL) of frequency-domain optical coherence tomography (fdOCT) scans of patients with glaucoma and glaucoma suspects. Peripapillary circle (1.7-mm radius) and cube optic disc fdOCT scans were obtained on 208 eyes from 110 patients (57.4 ± 13.2 years) with glaucomatous optic neuropathy (GON) and 45 eyes of 45 controls (48.0 ± 12.6 years) with normal results of fundus examination. Holes in the RNFL were identified independently by two observers on the circle scans. Holes were found in 33 (16%) eyes of 28 (25%) patients; they were not found in any of the control eyes. Twenty-four eyes had more than one hole. Although some holes were relatively large, others were small. In general, the holes were located adjacent to blood vessels; only three eyes had isolated holes that were not adjacent to a vessel. The holes tended to be in the regions that are thickest in healthy controls and were associated with arcuate defects in patients. Holes were not seen in the center of the temporal disc region. They were more common in the superior (25 eyes) than in the inferior (15 eyes) disc. Of the 30 eyes with holes with reliable visual fields, seven were glaucoma suspect eyes with normal visual fields. The holes in the RNFL seen in patients with GON were probably due to a local loss of RNFL fibers and can occur in the eyes of glaucoma suspects with normal visual fields.

Food-Predicting Stimuli Differentially Influence Eye Movements and Goal-Directed Behavior in Normal-Weight, Overweight, and Obese Individuals

PubMed Central

Lehner, Rea; Balsters, Joshua H.; Bürgler, Alexandra; Hare, Todd A.; Wenderoth, Nicole

2017-01-01

Obese individuals have been shown to exhibit abnormal sensitivity to rewards and reward-predicting cues as for example food-associated cues frequently used in advertisements. It has also been shown that food-associated cues can increase goal-directed behavior but it is currently unknown, whether this effect differs between normal-weight, overweight, and obese individuals. Here, we investigate this question by using a Pavlovian-to-instrumental transfer (PIT) task in normal-weight (N = 20), overweight (N = 17), and obese (N = 17) individuals. Furthermore, we applied eye tracking during Pavlovian conditioning to measure the participants’ conditioned response as a proxy of the incentive salience of the predicted reward. Our results show that the goal-directed behavior of overweight individuals was more strongly influenced by food-predicting cues (i.e., stronger PIT effect) than that of normal-weight and obese individuals (p < 0.001). The weight groups were matched for age, gender, education, and parental education. Eye movements during Pavlovian conditioning also differed between weight categories (p < 0.05) and were used to categorize individuals based on their fixation style into “high eye index” versus “low eye index” as well. Our main finding was that the fixation style exhibited a complex interaction with the weight category. Furthermore, we found that normal-weight individuals of the group “high eye index” had higher body mass index within the healthy range than individuals of the group “low eye index” (p < 0.001), but this relationship was not found within in the overweight or obese groups (p > 0.646). Our findings are largely consistent with the incentive sensitization theory predicting that overweight individuals are more susceptible to food-related cues than normal-weight controls. However, this hypersensitivity might be reduced in obese individuals, possibly due to habitual/compulsive overeating or differences in reward valuation. PMID:29180968

Food-Predicting Stimuli Differentially Influence Eye Movements and Goal-Directed Behavior in Normal-Weight, Overweight, and Obese Individuals.

PubMed

Lehner, Rea; Balsters, Joshua H; Bürgler, Alexandra; Hare, Todd A; Wenderoth, Nicole

2017-01-01

Obese individuals have been shown to exhibit abnormal sensitivity to rewards and reward-predicting cues as for example food-associated cues frequently used in advertisements. It has also been shown that food-associated cues can increase goal-directed behavior but it is currently unknown, whether this effect differs between normal-weight, overweight, and obese individuals. Here, we investigate this question by using a Pavlovian-to-instrumental transfer (PIT) task in normal-weight ( N  = 20), overweight ( N  = 17), and obese ( N  = 17) individuals. Furthermore, we applied eye tracking during Pavlovian conditioning to measure the participants' conditioned response as a proxy of the incentive salience of the predicted reward. Our results show that the goal-directed behavior of overweight individuals was more strongly influenced by food-predicting cues (i.e., stronger PIT effect) than that of normal-weight and obese individuals ( p  < 0.001). The weight groups were matched for age, gender, education, and parental education. Eye movements during Pavlovian conditioning also differed between weight categories ( p  < 0.05) and were used to categorize individuals based on their fixation style into "high eye index" versus "low eye index" as well. Our main finding was that the fixation style exhibited a complex interaction with the weight category. Furthermore, we found that normal-weight individuals of the group "high eye index" had higher body mass index within the healthy range than individuals of the group "low eye index" ( p  < 0.001), but this relationship was not found within in the overweight or obese groups ( p  > 0.646). Our findings are largely consistent with the incentive sensitization theory predicting that overweight individuals are more susceptible to food-related cues than normal-weight controls. However, this hypersensitivity might be reduced in obese individuals, possibly due to habitual/compulsive overeating or differences in reward valuation.

Amblyopia

MedlinePlus

Amblyopia, or "lazy eye," is the most common cause of visual impairment in children. It happens when an eye fails to work properly with the brain. The eye may look normal, but the brain favors the ...

Chromosomal Microarray versus Karyotyping for Prenatal Diagnosis

PubMed Central

Wapner, Ronald J.; Martin, Christa Lese; Levy, Brynn; Ballif, Blake C.; Eng, Christine M.; Zachary, Julia M.; Savage, Melissa; Platt, Lawrence D.; Saltzman, Daniel; Grobman, William A.; Klugman, Susan; Scholl, Thomas; Simpson, Joe Leigh; McCall, Kimberly; Aggarwal, Vimla S.; Bunke, Brian; Nahum, Odelia; Patel, Ankita; Lamb, Allen N.; Thom, Elizabeth A.; Beaudet, Arthur L.; Ledbetter, David H.; Shaffer, Lisa G.; Jackson, Laird

2013-01-01

Background Chromosomal microarray analysis has emerged as a primary diagnostic tool for the evaluation of developmental delay and structural malformations in children. We aimed to evaluate the accuracy, efficacy, and incremental yield of chromosomal microarray analysis as compared with karyotyping for routine prenatal diagnosis. Methods Samples from women undergoing prenatal diagnosis at 29 centers were sent to a central karyotyping laboratory. Each sample was split in two; standard karyotyping was performed on one portion and the other was sent to one of four laboratories for chromosomal microarray. Results We enrolled a total of 4406 women. Indications for prenatal diagnosis were advanced maternal age (46.6%), abnormal result on Down’s syndrome screening (18.8%), structural anomalies on ultrasonography (25.2%), and other indications (9.4%). In 4340 (98.8%) of the fetal samples, microarray analysis was successful; 87.9% of samples could be used without tissue culture. Microarray analysis of the 4282 nonmosaic samples identified all the aneuploidies and unbalanced rearrangements identified on karyotyping but did not identify balanced translocations and fetal triploidy. In samples with a normal karyotype, microarray analysis revealed clinically relevant deletions or duplications in 6.0% with a structural anomaly and in 1.7% of those whose indications were advanced maternal age or positive screening results. Conclusions In the context of prenatal diagnostic testing, chromosomal microarray analysis identified additional, clinically significant cytogenetic information as compared with karyotyping and was equally efficacious in identifying aneuploidies and unbalanced rearrangements but did not identify balanced translocations and triploidies. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and others; ClinicalTrials.gov number, NCT01279733.) PMID:23215555

The Role of Eye Movement Driven Attention in Functional Strabismic Amblyopia

PubMed Central

2015-01-01

Strabismic amblyopia “blunt vision” is a developmental anomaly that affects binocular vision and results in lowered visual acuity. Strabismus is a term for a misalignment of the visual axes and is usually characterized by impaired ability of the strabismic eye to take up fixation. Such impaired fixation is usually a function of the temporally and spatially impaired binocular eye movements that normally underlie binocular shifts in visual attention. In this review, we discuss how abnormal eye movement function in children with misaligned eyes influences the development of normal binocular visual attention and results in deficits in visual function such as depth perception. We also discuss how eye movement function deficits in adult amblyopia patients can also lead to other abnormalities in visual perception. Finally, we examine how the nonamblyopic eye of an amblyope is also affected in strabismic amblyopia. PMID:25838941

caCORRECT2: Improving the accuracy and reliability of microarray data in the presence of artifacts

PubMed Central

2011-01-01

Background In previous work, we reported the development of caCORRECT, a novel microarray quality control system built to identify and correct spatial artifacts commonly found on Affymetrix arrays. We have made recent improvements to caCORRECT, including the development of a model-based data-replacement strategy and integration with typical microarray workflows via caCORRECT's web portal and caBIG grid services. In this report, we demonstrate that caCORRECT improves the reproducibility and reliability of experimental results across several common Affymetrix microarray platforms. caCORRECT represents an advance over state-of-art quality control methods such as Harshlighting, and acts to improve gene expression calculation techniques such as PLIER, RMA and MAS5.0, because it incorporates spatial information into outlier detection as well as outlier information into probe normalization. The ability of caCORRECT to recover accurate gene expressions from low quality probe intensity data is assessed using a combination of real and synthetic artifacts with PCR follow-up confirmation and the affycomp spike in data. The caCORRECT tool can be accessed at the website: http://cacorrect.bme.gatech.edu. Results We demonstrate that (1) caCORRECT's artifact-aware normalization avoids the undesirable global data warping that happens when any damaged chips are processed without caCORRECT; (2) When used upstream of RMA, PLIER, or MAS5.0, the data imputation of caCORRECT generally improves the accuracy of microarray gene expression in the presence of artifacts more than using Harshlighting or not using any quality control; (3) Biomarkers selected from artifactual microarray data which have undergone the quality control procedures of caCORRECT are more likely to be reliable, as shown by both spike in and PCR validation experiments. Finally, we present a case study of the use of caCORRECT to reliably identify biomarkers for renal cell carcinoma, yielding two diagnostic biomarkers with potential clinical utility, PRKAB1 and NNMT. Conclusions caCORRECT is shown to improve the accuracy of gene expression, and the reproducibility of experimental results in clinical application. This study suggests that caCORRECT will be useful to clean up possible artifacts in new as well as archived microarray data. PMID:21957981

Effects of Device on Video Head Impulse Test (vHIT) Gain.

PubMed

Janky, Kristen L; Patterson, Jessie N; Shepard, Neil T; Thomas, Megan L A; Honaker, Julie A

2017-10-01

Numerous video head impulse test (vHIT) devices are available commercially; however, gain is not calculated uniformly. An evaluation of these devices/algorithms in healthy controls and patients with vestibular loss is necessary for comparing and synthesizing work that utilizes different devices and gain calculations. Using three commercially available vHIT devices/algorithms, the purpose of the present study was to compare: (1) horizontal canal vHIT gain among devices/algorithms in normal control subjects; (2) the effects of age on vHIT gain for each device/algorithm in normal control subjects; and (3) the clinical performance of horizontal canal vHIT gain between devices/algorithms for differentiating normal versus abnormal vestibular function. Prospective. Sixty-one normal control adult subjects (range 20-78) and eleven adults with unilateral or bilateral vestibular loss (range 32-79). vHIT was administered using three different devices/algorithms, randomized in order, for each subject on the same day: (1) Impulse (Otometrics, Schaumberg, IL; monocular eye recording, right eye only; using area under the curve gain), (2) EyeSeeCam (Interacoustics, Denmark; monocular eye recording, left eye only; using instantaneous gain), and (3) VisualEyes (MicroMedical, Chatham, IL, binocular eye recording; using position gain). There was a significant mean difference in vHIT gain among devices/algorithms for both the normal control and vestibular loss groups. vHIT gain was significantly larger in the ipsilateral direction of the eye used to measure gain; however, in spite of the significant mean differences in vHIT gain among devices/algorithms and the significant directional bias, classification of "normal" versus "abnormal" gain is consistent across all compared devices/algorithms, with the exception of instantaneous gain at 40 msec. There was not an effect of age on vHIT gain up to 78 years regardless of the device/algorithm. These findings support that vHIT gain is significantly different between devices/algorithms, suggesting that care should be taken when making direct comparisons of absolute gain values between devices/algorithms. American Academy of Audiology

Normative database of donor keratographic readings in an eye-bank setting.

PubMed

Lewis, Jennifer R; Bogucki, Jennifer M; Mahmoud, Ashraf M; Lembach, Richard G; Roberts, Cynthia J

2010-04-01

To generate a normative donor topographic database from rasterstereography images of whole globes acquired in an eye-bank setting with minimal manipulation or handling. Eye-bank laboratory. In a retrospective study, rasterstereography topographic images that had been prospectively collected in duplicate of donor eyes received by the Central Ohio Lions Eye Bank between 1997 and 1999 were analyzed. Best-fit sphere (BFS) and simulated keratometry (K) values were extracted. These values were recalculated after application of custom software to correct any tilt of the mapped surfaces relative to the image plane. The mean value variances between right eyes and left eyes, between consecutive scans, and after untilting were analyzed by repeated-measures analysis of variance and t tests (P.05, Kolmogorov-Smirnov). There was no difference between right and left eyes or consecutive scans (P>.05). The mean values changed when the images were tilt-corrected (P<.05). The right eye BFS, Kflat, and Ksteep values of 42.03 diopters (D) +/- 1.88 (SD), 42.21 +/- 2.10 D, and 43.82 +/- 2.00 D, respectively, increased to 42.52 +/- 1.73 D, 43.05 +/- 1.99 D, and 44.57 +/- 2.02 D, respectively, after tilt correction. Keratometric parameter frequency distributions from the donor database of tilt-corrected data were normal in distribution and comparable to parameters reported for normal eyes in a living population. These findings show the feasibility and reliability of routine donor-eye topography by rasterstereography. No author has a financial or proprietary interest in any material or method mentioned. Additional disclosures are found in the footnotes. Copyright (c) 2010 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

Effect of mistletoe combined with carboxymethyl cellulose on dry eye in postmenopausal women

PubMed Central

Jiang, Nan; Ye, Lin-Hong; Ye, Lei; Yu, Jing; Yang, Qi-Chen; Yuan, Qing; Zhu, Pei-Wen; Shao, Yi

2017-01-01

AIM To investigate the protective effect of mistletoe combined with carboxymethyl cellulose eye drops on dry eye in postmenopausal women. METHODS Sixty postmenopause female patients diagnosed of dry eye were assigned randomly to mistletoe combined with carboxymethyl cellulose eye drops treatment group (n=30) and control group treated with normal saline eye drops (n=30). The subjective symptoms of ocular surface, Ocular Surface Disease Index (OSDI), tear film function tests, tear protein and corneal morphology by confocal scanning microscopy were analyzed before treatment and at 1, 2, 4 and 8wk after treatment respectively. To ensure the safety of the trial, all patients were examined with systolic pressure, diastolic pressure, glutamic-pyruvic transaminase, glutamic oxaloacetic transaminase, urine creatinine, and blood urea nitrogen at 8wk after treatment. RESULTS There were no obvious differences between two groups before the treatment (P>0.05). In two months after the treatment, the symptoms of ocular surface, OSDI, tear protein, and tear film function were only slightly changed in normal saline eye drops group. However, all indices were improved after the treatment of mistletoe combined with carboxymethyl cellulose eye drops group (P<0.05). In addition, the average amount of corneal epithelium basal cells and inflammatory cells of mistletoe treated group were 3174±379 and 38±25 cells/mm2, significantly decreased as compared to the control group with 4309±612 and 158± 61 cells/mm2, respectively. In the control group, although nerves still maintained straight under corneal epithelium, the number of nerves were significantly decreased, as compared with normal female. In the mistletoe treated group, the number of nerves was only slightly reduced, compared with normal female. CONCLUSION Mistletoe combined with carboxymethyl cellulose eye drops can alleviate the symptoms and signs of dry eye symptoms. PMID:29181309

Comparison of optic disc topography in non-glaucomatous eyes of children with juvenile diabetes mellitus and normal children.

PubMed

Elgin, Ufuk; Cankaya, Bülent; Simsek, Tulay; Batman, Aygen

2010-01-01

To compare the optic disc topography parameters of children with juvenile diabetes mellitus and normal children using the Heidelberg Retinal Tomograph (HRT III) (Heidelberg Engineering, Heidelberg, Germany). The topographic optic disc parameters (cup volume, cup area, rim volume, rim area, disc area, mean cup-to-disc ratio, and mean cup depth) of 28 non-glaucomatous eyes of 28 children with type 1 diabetes mellitus and 28 eyes of 28 age-matched healthy children were compared using the nonparametric Mann-Whitney U test. No statistically significant differences were found between cup volume (P = .782), cup area (P = .878), rim volume (P = .853), disc area (P = .452), mean cup-to-disc ratio (P = .852), and mean cup depth (P = .711) of eyes of cases with diabetes mellitus and normal subjects. This result suggests that non-glaucomatous eyes of children with type 1 diabetes mellitus and healthy subjects have similar topographic optic disc characteristics. Copyright 2010, SLACK Incorporated.

GenePublisher: Automated analysis of DNA microarray data.

PubMed

Knudsen, Steen; Workman, Christopher; Sicheritz-Ponten, Thomas; Friis, Carsten

2003-07-01

GenePublisher, a system for automatic analysis of data from DNA microarray experiments, has been implemented with a web interface at http://www.cbs.dtu.dk/services/GenePublisher. Raw data are uploaded to the server together with a specification of the data. The server performs normalization, statistical analysis and visualization of the data. The results are run against databases of signal transduction pathways, metabolic pathways and promoter sequences in order to extract more information. The results of the entire analysis are summarized in report form and returned to the user.

Wolf-Hirschhorn Syndrome with Epibulbar Dermoid: An Unusual Association in a Patient with 4p Deletion and Functional Xp Disomy.

PubMed

Bragagnolo, Silvia; Colovati, Mileny E S; Guilherme, Roberta S; Dantas, Anelisa G; de Souza, Malú Zamariolli; de Soares, Maria F; Melaragno, Maria I; Perez, Ana B

2016-01-01

Wolf-Hirschhorn syndrome (WHS) is a contiguous gene and multiple malformation syndrome that results from a deletion in the 4p16.3 region. We describe here a 6-month-old girl that presented with WHS features but also displayed unusual findings, such as epibulbar dermoid in the left eye, ear tags, and left microtia. Although on G-banding her karyotype appeared to be normal, chromosomal microarray analysis revealed an ∼13-Mb 4p16.3p15.33 deletion and an ∼9-Mb Xp22.33p22.31 duplication, resulting from a balanced maternal t(X;4)(p22.31;p15.33) translocation. The patient presented with functional Xp disomy due to an unbalanced X-autosome translocation, a rare cytogenetic finding in females with unbalanced rearrangements. Sequencing of both chromosome breakpoints detected no gene disruption. To the best of our knowledge, this is the first patient described in the literature with WHS and epibulbar dermoid, a typical characteristic of the oculoauriculovertebral spectrum (OAVS). Our data suggest that possible candidate genes for OAVS may have been deleted along with the WHS critical region. © 2016 S. Karger AG, Basel.

Measuring eye movements during locomotion: filtering techniques for obtaining velocity signals from a video-based eye monitor

NASA Technical Reports Server (NTRS)

Das, V. E.; Thomas, C. W.; Zivotofsky, A. Z.; Leigh, R. J.

1996-01-01

Video-based eye-tracking systems are especially suited to studying eye movements during naturally occurring activities such as locomotion, but eye velocity records suffer from broad band noise that is not amenable to conventional filtering methods. We evaluated the effectiveness of combined median and moving-average filters by comparing prefiltered and postfiltered records made synchronously with a video eye-tracker and the magnetic search coil technique, which is relatively noise free. Root-mean-square noise was reduced by half, without distorting the eye velocity signal. To illustrate the practical use of this technique, we studied normal subjects and patients with deficient labyrinthine function and compared their ability to hold gaze on a visual target that moved with their heads (cancellation of the vestibulo-ocular reflex). Patients and normal subjects performed similarly during active head rotation but, during locomotion, patients held their eyes more steadily on the visual target than did subjects.

Determination of the toxicity of intravitreal minocycline in rabbit eyes.

PubMed

Falavarjani, Khalil Ghasemi; Pourhabibi, Arash; Aghdam, Kaveh Abri; Hosseini, Seyed Bagher; Modarres, Mehdi; Pazouki, Abdolreza; Khanamiri, Hossein Nazari

2016-09-01

To evaluate the retinal toxicity of intravitreal minocycline in rabbit eyes. Intravitreal injection of minocycline with concentrations of 1000, 500, 250, 125 and 62.5 μg in 0.1 ml was performed in 10 New Zealand albino rabbits. Each concentration was injected into two rabbit eyes. For each dose, normal saline was injected in one contralateral eye and the other fellow eye remained non-injected. Electrophysiologic testing was performed before and 4 weeks after injections. The eyes were enucleated 4 weeks after injections and examined using light microscopy. The clinical examination was unremarkable after injections. Electroretinography recordings were significantly affected at all doses in at least one of the a- or b-waves of photopic or scotopic responses. Histopathologic examination revealed marked atrophy and loss of integrity in all retinal layers in all minocycline injected eyes. Contralateral eyes were normal. In our study, intravitreal minocycline was toxic to the retina in albino rabbits even at a concentration of 62.5 µg/0.1 ml.

P gene as an inherited biomarker of human eye color.

PubMed

Rebbeck, Timothy R; Kanetsky, Peter A; Walker, Amy H; Holmes, Robin; Halpern, Allan C; Schuchter, Lynn M; Elder, David E; Guerry, DuPont

2002-08-01

Human pigmentation, including eye color, has been associated with skin cancer risk. The P gene is the human homologue to the mouse pink-eye dilution locus and is responsible for oculocutaneous albinism type 2 and other phenotypes that confer eye hypopigmentation. The P gene is located on chromosome 15q11.2-q12, which is also the location of a putative eye pigmentation gene (EYCL3) inferred to exist by linkage analysis. Therefore, the P gene is a strong candidate for determination of human eye color. Using a sample of 629 normally pigmented individuals, we found that individuals were less likely to have blue or gray eyes if they had P gene variants Arg305Trp (P = 0.002), Arg419Gln (P = 0.001), or the combination of both variants (P = 0.003). These results suggest that P gene, in part, determines normal phenotypic variation in human eye color and may therefore represent an inherited biomarker of cutaneous cancer risk.

Removing Batch Effects from Longitudinal Gene Expression - Quantile Normalization Plus ComBat as Best Approach for Microarray Transcriptome Data

PubMed Central

Müller, Christian; Schillert, Arne; Röthemeier, Caroline; Trégouët, David-Alexandre; Proust, Carole; Binder, Harald; Pfeiffer, Norbert; Beutel, Manfred; Lackner, Karl J.; Schnabel, Renate B.; Tiret, Laurence; Wild, Philipp S.; Blankenberg, Stefan

2016-01-01

Technical variation plays an important role in microarray-based gene expression studies, and batch effects explain a large proportion of this noise. It is therefore mandatory to eliminate technical variation while maintaining biological variability. Several strategies have been proposed for the removal of batch effects, although they have not been evaluated in large-scale longitudinal gene expression data. In this study, we aimed at identifying a suitable method for batch effect removal in a large study of microarray-based longitudinal gene expression. Monocytic gene expression was measured in 1092 participants of the Gutenberg Health Study at baseline and 5-year follow up. Replicates of selected samples were measured at both time points to identify technical variability. Deming regression, Passing-Bablok regression, linear mixed models, non-linear models as well as ReplicateRUV and ComBat were applied to eliminate batch effects between replicates. In a second step, quantile normalization prior to batch effect correction was performed for each method. Technical variation between batches was evaluated by principal component analysis. Associations between body mass index and transcriptomes were calculated before and after batch removal. Results from association analyses were compared to evaluate maintenance of biological variability. Quantile normalization, separately performed in each batch, combined with ComBat successfully reduced batch effects and maintained biological variability. ReplicateRUV performed perfectly in the replicate data subset of the study, but failed when applied to all samples. All other methods did not substantially reduce batch effects in the replicate data subset. Quantile normalization plus ComBat appears to be a valuable approach for batch correction in longitudinal gene expression data. PMID:27272489

Eye and head motion during head turns in spaceflight

NASA Technical Reports Server (NTRS)

Thornton, William E.; Uri, John J.; Moore, Thomas P.; Pool, Sam L.

1988-01-01

Eye-head motion was studied pre-, in- and postflight during single voluntary head turns. A transient increase in vestibulo-ocular reflex (VOR) gain occurred early in the flight, but later trended toward normal. This increased gain was produced by a relative increase in eye counterrotation velocity. Asymmetries in gain with right and left turns also occurred, caused by asymmetries in eye counterrotation velocities. These findings were remarkably similar to those from Soviet primate studies using gaze fixation targets, except the human study trended more rapidly toward normal. These findings differ substantially from those measuring VOR gain by head oscillation, in which no significant changes were found inflight. No visual disturbances were noted in either test condition or in normal activities. These head turn studies are the only ones to date documenting any functional change in VOR in weightlessness.

Comparing multifocal VEP and standard automated perimetry in high-risk ocular hypertension and early glaucoma.

PubMed

Fortune, Brad; Demirel, Shaban; Zhang, Xian; Hood, Donald C; Patterson, Emily; Jamil, Annisa; Mansberger, Steven L; Cioffi, George A; Johnson, Chris A

2007-03-01

To compare the diagnostic performance of multifocal visual evoked potential (mfVEP) and standard automated perimetry (SAP), in eyes with high-risk ocular hypertension or early glaucoma. Both eyes of 185 individuals with high-risk ocular hypertension or early glaucoma were evaluated. Subjects ranged in age from 37 to 87 (mean +/- SD: 61 +/- 11 years). Pattern-reversal mfVEPs were obtained by using VERIS (Electro-Diagnostic Imaging, San Mateo, CA) with a four-electrode array and were analyzed with custom software. SAP visual fields (SITA-standard; Carl Zeiss Meditec, Inc., Dublin, CA) were obtained within 22.3 +/- 27.0 days of the mfVEP. Stereo disc photographs and Heidelberg Retina Tomograph (HRT) images were obtained during one visit, which was within 24.8 +/- 50.4 days of the mfVEP and 33.1 +/- 62.9 days of the SAP visual field. Abnormalities on the mfVEP were defined by using a variety of cluster criteria: SAP with pattern standard deviation (PSD) P

Lasik eye surgery - slideshow

MedlinePlus

... this page: //medlineplus.gov/ency/presentations/100206.htm Lasik eye surgery - series—Normal anatomy To use the ... A.M. Editorial team. Related MedlinePlus Health Topics Laser Eye Surgery A.D.A.M., Inc. is accredited by ...

Correlation of outer nuclear layer thickness with cone density values in patients with retinitis pigmentosa and healthy subjects.

PubMed

Menghini, Moreno; Lujan, Brandon J; Zayit-Soudry, Shiri; Syed, Reema; Porco, Travis C; Bayabo, Kristine; Carroll, Joseph; Roorda, Austin; Duncan, Jacque L

2014-12-16

We studied the correlation between outer nuclear layer (ONL) thickness and cone density in normal eyes and eyes with retinitis pigmentosa (RP). Spectral-domain optical coherence tomography (SD-OCT) scans were acquired using a displaced pupil entry position of the scanning beam to distinguish Henle's fiber layer from the ONL in 20 normal eyes (10 subjects) and 12 eyes with RP (7 patients). Cone photoreceptors were imaged using adaptive optics scanning laser ophthalmoscopy. The ONL thickness and cone density were measured at 0.5° intervals along the horizontal meridian through the fovea nasally and temporally. The ONL thickness and cone density were correlated using Spearman's rank correlation coefficient r. Cone densities averaged over the central 6° were lower in eyes with RP than normal, but showed high variability in both groups. The ONL thickness and cone density were significantly correlated when all retinal eccentricities were combined (r = 0.74); the correlation for regions within 0.5° to 1.5° eccentricity was stronger (r = 0.67) than between 1.5° and 3.0° eccentricity (r = 0.23). Although cone densities were lower between 0.5° and 1.5° in eyes with RP, ONL thickness measures at identical retinal locations were similar in the two groups (P = 0.31), and interindividual variation was high for ONL and cone density measures. Although ONL thickness and retinal eccentricity were important predictors of cone density, eccentricity was over 3 times more important. The ONL thickness and cone density were correlated in normal eyes and eyes with RP, but both were strongly correlated with retinal eccentricity, precluding estimation of cone density from ONL thickness. (ClinicalTrials.gov number, NCT00254605.). Copyright 2015 The Association for Research in Vision and Ophthalmology, Inc.

Correlation of Outer Nuclear Layer Thickness With Cone Density Values in Patients With Retinitis Pigmentosa and Healthy Subjects

PubMed Central

Menghini, Moreno; Lujan, Brandon J.; Zayit-Soudry, Shiri; Syed, Reema; Porco, Travis C.; Bayabo, Kristine; Carroll, Joseph; Roorda, Austin; Duncan, Jacque L.

2015-01-01

Purpose. We studied the correlation between outer nuclear layer (ONL) thickness and cone density in normal eyes and eyes with retinitis pigmentosa (RP). Methods. Spectral-domain optical coherence tomography (SD-OCT) scans were acquired using a displaced pupil entry position of the scanning beam to distinguish Henle's fiber layer from the ONL in 20 normal eyes (10 subjects) and 12 eyes with RP (7 patients). Cone photoreceptors were imaged using adaptive optics scanning laser ophthalmoscopy. The ONL thickness and cone density were measured at 0.5° intervals along the horizontal meridian through the fovea nasally and temporally. The ONL thickness and cone density were correlated using Spearman's rank correlation coefficient r. Results. Cone densities averaged over the central 6° were lower in eyes with RP than normal, but showed high variability in both groups. The ONL thickness and cone density were significantly correlated when all retinal eccentricities were combined (r = 0.74); the correlation for regions within 0.5° to 1.5° eccentricity was stronger (r = 0.67) than between 1.5° and 3.0° eccentricity (r = 0.23). Although cone densities were lower between 0.5° and 1.5° in eyes with RP, ONL thickness measures at identical retinal locations were similar in the two groups (P = 0.31), and interindividual variation was high for ONL and cone density measures. Although ONL thickness and retinal eccentricity were important predictors of cone density, eccentricity was over 3 times more important. Conclusions. The ONL thickness and cone density were correlated in normal eyes and eyes with RP, but both were strongly correlated with retinal eccentricity, precluding estimation of cone density from ONL thickness. (ClinicalTrials.gov number, NCT00254605.) PMID:25515570

Role of percent tissue altered on ectasia after LASIK in eyes with suspicious topography.

PubMed

Santhiago, Marcony R; Smadja, David; Wilson, Steven E; Krueger, Ronald R; Monteiro, Mario L R; Randleman, J Bradley

2015-04-01

To investigate the association of the percent tissue altered (PTA) with the occurrence of ectasia after LASIK in eyes with suspicious preoperative corneal topography. This retrospective comparative case-control study compared associations of reported ectasia risk factors in 129 eyes, including 57 eyes with suspicious preoperative Placido-based corneal topography that developed ectasia after LASIK (suspect ectasia group), 32 eyes with suspicious topography that remained stable for at least 3 years after LASIK (suspect control group), and 30 eyes that developed ectasia with bilateral normal topography (normal topography ectasia group). Groups were subdivided based on topographic asymmetry into high- or low-suspect groups. The PTA, preoperative central corneal thickness (CCT), residual stromal bed (RSB), and age (years) were evaluated in univariate and multivariate analyses. Average PTA values for normal topography ectasia (45), low-suspect ectasia (39), high-suspect ectasia (36), low-suspect control (32), and high-suspect control (29) were significantly different from one another in all comparisons (P < .003) except high- and low-suspect ectasia groups (P = .033), and presented the highest discriminative capability of all variables evaluated. Age was only significantly different between the high-suspect ectasia and normal topography ectasia groups, and CCT was not significantly different between any groups. Stepwise logistic regression revealed the PTA as the most significant independent variable (P < .0001), with RSB the next most significant parameter. There remains a significant correlation between PTA values and ectasia risk after LASIK, even in eyes with suspicious corneal topography. Less tissue alteration, or a lower PTA value, was necessary to induce ectasia in eyes with more remarkable signs of topographic abnormality, and PTA provided better discriminative capabilities than RSB for all study populations. Copyright 2015, SLACK Incorporated.

Gene expression signatures in tree shrew choroid in response to three myopiagenic conditions

PubMed Central

He, Li; Frost, Michael R.; Siegwart, John T.; Norton, Thomas T.

2014-01-01

We examined gene expression in tree shrew choroid in response to three different myopiagenic conditions: minus lens (ML) wear, form deprivation (FD), and continuous darkness (DK). Four groups of tree shrews (n = 7 per group) were used. Starting 24 days after normal eye opening (days of visual experience [DVE]), the ML group wore a monocular −5 D lens for 2 days. The FD group wore a monocular translucent diffuser for 2 days. The DK group experienced continuous darkness binocularly for 11 days, starting at 17 DVE. An age-matched normal group was examined at 26 DVE. Quantitative PCR was used to measure the relative (treated eye vs. control eye) differences in mRNA levels in the choroid for 77 candidate genes. Small myopic changes were observed in the treated eyes (relative to the control eyes) of the ML group (−1.0 ± 0.2 D; mean ± SEM) and FD group (−1.9 ± 0.2 D). A larger myopia developed in the DK group (−4.4 ± 1.0 D) relative to Normal eyes (both groups, mean of right and left eyes). In the ML group, 28 genes showed significant differential mRNA expression; eighteen were down-regulated. A very similar pattern occurred in the FD group; twenty-seven of the same genes were similarly regulated, along with five additional genes. Fewer expression differences in the DK group were significant compared to normal or the control eyes of the ML and FD groups, but the pattern was similar to that of the ML and FD differential expression patterns. These data suggest that, at the level of the choroid, the gene expression signatures produced by “GO” emmetropization signals are highly similar despite the different visual conditions. PMID:25072854

Morphological Alterations Within the Peripheral Fixation of the Iris Dilator Muscle in Eyes With Pigmentary Glaucoma

PubMed Central

Flügel-Koch, Cassandra M.; Tektas, Ozan Y.; Kaufman, Paul L.; Paulsen, Friedrich P.; Lütjen-Drecoll, Elke

2014-01-01

Purpose. To analyze the peripheral fixation of the iris dilator muscle in normal eyes and in eyes with pigmentary glaucoma (PG). Methods. Using 63 control eyes (age 18 months–99 years), the peripheral iris dilator was investigated by light microscopy, immunohistochemistry, and electron microscopy. Development was studied using 18 differently aged fetal eyes stained immunohistochemically against α-smooth muscle (SM) actin. The peripheral iris dilator muscle in PG was analyzed using semithin and ultrathin sections of six glutaraldehyde-fixed eyes from three donors aged 38, 62, and 74 years. Results. In normal eyes, the peripheral end of the iris dilator muscle is arranged in a sphincter-like manner. Arcade-shaped tendinous connections associated with myofibroblasts (iridial strands) anchor the iris dilator within the elastic–fibromuscular ciliary meshwork that also serves as fixation area for the elastic tendons of the inner ciliary muscle portions. The iridial strands are innervated and can adapt their length during accommodation. The PG eyes show incomplete circular bundles and iridial strands that are mainly anchored to the iris stroma and the flexible uveal parts of the trabecular meshwork. Conclusions. The normal anchorage of the peripheral iris dilator and its presumably neuronally regulated length adaptation stabilize the peripheral iris during accommodation. Insufficient fixation in PG could promote posterior bowing of the iris with rubbing against the zonular fibers and pigment liberation from the iris pigmented epithelium. PMID:24938519

Highly sensitive detection of multiple tumor markers for lung cancer using gold nanoparticle probes and microarrays.

PubMed

Gao, Wanlei; Wang, Wentao; Yao, Shihua; Wu, Shan; Zhang, Honglian; Zhang, Jishen; Jing, Fengxiang; Mao, Hongju; Jin, Qinghui; Cong, Hui; Jia, Chunping; Zhang, Guojun; Zhao, Jianlong

2017-03-15

Assay of multiple serum tumor markers such as carcinoembryonic antigen (CEA), cytokeratin 19 fragment antigen (CYFRA21-1), and neuron specific enolase (NSE), is important for the early diagnosis of lung cancer. Dickkopf-1 (DKK1), a novel serological and histochemical biomarker, was recently reported to be preferentially expressed in lung cancer. Four target proteins were sandwiched by capture antibodies attached to microarrays and detection antibodies carried on modified gold nanoparticles. Optical signals generated by the sandwich structures were amplified by gold deposition with HAuCl 4 and H 2 O 2 , and were observable by microscopy or the naked eye. The four tumor markers were subsequently measured in 106 lung cancer patients and 42 healthy persons. The assay was capable of detecting multiple biomarkers in serum sample at concentration of <1 ng mL -1 in 1 h. Combined detection of the four tumor markers highly improved the sensitivity (to 87.74%) for diagnosis of lung cancer compared with sensitivity of single markers. A rapid, highly sensitive co-detection method for multiple biomarkers based on gold nanoparticles and microarrays was developed. In clinical use, it would be expected to improve the early diagnosis of lung cancer. Copyright © 2016 Elsevier B.V. All rights reserved.

Spdef Null Mice Lack Conjunctival Goblet Cells and Provide a Model of Dry Eye

PubMed Central

Marko, Christina K.; Menon, Balaraj B.; Chen, Gang; Whitsett, Jeffrey A.; Clevers, Hans; Gipson, Ilene K.

2014-01-01

Goblet cell numbers decrease within the conjunctival epithelium in drying and cicatrizing ocular surface diseases. Factors regulating goblet cell differentiation in conjunctival epithelium are unknown. Recent data indicate that the transcription factor SAM-pointed domain epithelial-specific transcription factor (Spdef) is essential for goblet cell differentiation in tracheobronchial and gastrointestinal epithelium of mice. Using Spdef−/− mice, we determined that Spdef is required for conjunctival goblet cell differentiation and that Spdef−/− mice, which lack conjunctival goblet cells, have significantly increased corneal surface fluorescein staining and tear volume, a phenotype consistent with dry eye. Microarray analysis of conjunctival epithelium in Spdef−/− mice revealed down-regulation of goblet cell–specific genes (Muc5ac, Tff1, Gcnt3). Up-regulated genes included epithelial cell differentiation/keratinization genes (Sprr2h, Tgm1) and proinflammatory genes (Il1-α, Il-1β, Tnf-α), all of which are up-regulated in dry eye. Interestingly, four Wnt pathway genes were down-regulated. SPDEF expression was significantly decreased in the conjunctival epithelium of Sjögren syndrome patients with dry eye and decreased goblet cell mucin expression. These data demonstrate that Spdef is required for conjunctival goblet cell differentiation and down-regulation of SPDEF may play a role in human dry eye with goblet cell loss. Spdef−/− mice have an ocular surface phenotype similar to that in moderate dry eye, providing a new, more convenient model for the disease. PMID:23665202

Spdef null mice lack conjunctival goblet cells and provide a model of dry eye.

PubMed

Marko, Christina K; Menon, Balaraj B; Chen, Gang; Whitsett, Jeffrey A; Clevers, Hans; Gipson, Ilene K

2013-07-01

Goblet cell numbers decrease within the conjunctival epithelium in drying and cicatrizing ocular surface diseases. Factors regulating goblet cell differentiation in conjunctival epithelium are unknown. Recent data indicate that the transcription factor SAM-pointed domain epithelial-specific transcription factor (Spdef) is essential for goblet cell differentiation in tracheobronchial and gastrointestinal epithelium of mice. Using Spdef(-/-) mice, we determined that Spdef is required for conjunctival goblet cell differentiation and that Spdef(-/-) mice, which lack conjunctival goblet cells, have significantly increased corneal surface fluorescein staining and tear volume, a phenotype consistent with dry eye. Microarray analysis of conjunctival epithelium in Spdef(-/-) mice revealed down-regulation of goblet cell-specific genes (Muc5ac, Tff1, Gcnt3). Up-regulated genes included epithelial cell differentiation/keratinization genes (Sprr2h, Tgm1) and proinflammatory genes (Il1-α, Il-1β, Tnf-α), all of which are up-regulated in dry eye. Interestingly, four Wnt pathway genes were down-regulated. SPDEF expression was significantly decreased in the conjunctival epithelium of Sjögren syndrome patients with dry eye and decreased goblet cell mucin expression. These data demonstrate that Spdef is required for conjunctival goblet cell differentiation and down-regulation of SPDEF may play a role in human dry eye with goblet cell loss. Spdef(-/-) mice have an ocular surface phenotype similar to that in moderate dry eye, providing a new, more convenient model for the disease. Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

A comparison of preservative-free diclofenac and preserved diclofenac eye drops after cataract surgery in patients with diabetic retinopathy.

PubMed

Yasuda, Kanako; Miyazawa, Akiko; Shimura, Masahiko

2012-06-01

The aim of this study was to compare the anti-inflammatory efficacy of preservative-free and preserved 0.1% diclofenac eye drops for the management of postoperative inflammation after cataract surgery in patients with nonproliferative diabetic retinopathy and in normal controls. Forty-two diabetic patients and 50 normal control patients who underwent small-incision phacoemulsification cataract surgery bilaterally received topical preservative-free diclofenac in 1 eye and preserved diclofenac in the other eye. The corrected distance visual acuity (CDVA) as determined by a logarithm of the minimum angle of resolution (logMAR) chart, intraocular pressure (IOP), foveal thickness (FT) using optical coherence tomography (OCT), and the anterior chamber flare (ACF) score measured with a laser flare cell meter were monitored for 12 weeks after surgery. In the eyes with diabetic retinopathy, there were no significant differences in CDVA, IOP, FT, and ACF score between the right and left eyes at the initial exam. After cataract surgery, changes in CDVA, IOP, and FT were not influenced by the preservative in the diclofenac eye drops. In contrast, the ACF score in the eyes treated with preserved diclofenac showed slower recovery from postoperative inflammation than the eyes treated with preservative-free diclofenac. In the normal control eyes, similar but milder changes were observed in each of the clinical parameters. Because preservative suppressed the anti-inflammatory efficacy of topical diclofenac after cataract surgery, preservative-free diclofenac may have an improved safety profile during postoperative treatment, especially in patients with diabetic retinopathy.

Your Aging Eyes: How You See as Time Goes By

MedlinePlus

... Lengthen Life Keep an Eye on Your Eyes Building Social Bonds Coping with Caregiving Wise Choices Protect Your Vision Have a comprehensive eye exam each year after age 50. Stop smoking. Eat a diet rich in green, leafy vegetables and fish. Exercise. Maintain normal blood ...

Hyperosmolarity response of ocular standing potential as a clinical test for retinal pigment epithelium activity. Chorioretinal dystrophies.

PubMed

Yonemura, D; Kawasaki, K; Madachi-Yamamoto, S

1984-05-30

The hyperosmolarity response of the standing potential was recorded in retinitis pigmentosa (20 eyes), central (pericentral) retinitis pigmentosa (4 eyes), pigmented paravenous retinochoroidal atrophy (2 eyes), fundus albipunctatus (8 eyes), and Stargardt's disease (or fundus flavimaculatus) (14 eyes). The light peak/dark trough ratio (the L/D ratio) and the Diamox response were also determined. The hyperosmolarity response was greatly suppressed (less than M-4SD; M and SD indicate respectively the mean and the standard deviation in normal control subjects) in all examined eyes with retinitis pigmentosa (20 eyes) including retinitis pigmentosa sine pigmento (8 eyes), central (pericentral) retinitis pigmentosa (4 eyes), and pigmented paravenous retinochoroidal atrophy (2 eyes). The L/D ratio was larger than 1.26 (M-2.5 SD) in the half of the eyes with the above-described diseases. The hyperosmolarity response was abnormal (less than M-2 SD) in 4 of 8 eyes with fundus albipunctatus. The L/D ratio was normal in all 8 eyes. The hyperosmolarity response was abnormal (less than M-2 SD) in all 14 eyes with Stargardt's disease or fundus flavimaculatus. The L/D ratio was abnormal in 5 of these 14 eyes. The hyperosmolarity response was more frequently abnormal than the L/D ratio in the chorioretinal dystrophies mentioned above, and hence is useful particularly for early diagnosis of these disorders.

Hyperosmolarity response of ocular standing potential as a clinical test for retinal pigment epithelium activity chorioretinal dystrophies.

PubMed

Yonemura, D; Kawasaki, K; Madachi-Yamamoto, S

1984-05-01

The hyperosmolarity response of the standing potential was recorded in retinitis pigmentosa (20 eyes), central (pericentral) retinitis pigmentosa (4 eyes), pigmented paravenous retinochoroidal atrophy (2 eyes), fundus albipunctatus (8 eyes), and Stargardt's disease (or fundus flavimaculatus) (14 eyes). The light peak/dark trough ratio (the L/D ratio) and the Diamox response were also determined.The hyperosmolarity response was greatly suppressed (less than M-4SD; M and SD indicate respectively the mean and the standard deviation in normal control subjects) in all examined eyes with retinitis pigmentosa (20 eyes) including retinitis pigmentosa sine pigmento (8 eyes), central (pericentral) retinitis pigmentosa (4 eyes), and pigmented paravenous retinochoroidal atrophy (2 eyes). The L/D ratio was larger than 1.26 (M-2.5 SD) in the half of the eyes with the above-described diseases.The hyperosmolarity response was abnormal (less than M-2 SD) in 4 of 8 eyes with fundus albipunctatus. The L/D ratio was normal in all 8 eyes.The hyperosmolarity response was abnormal (less than M-2 SD) in all 14 eyes with Stargardt's disease or fundus flavimaculatus. The L/D ratio was abnormal in 5 of these 14 eyes.The hyperosmolarity response was more frequently abnormal than the L/D ratio in the chorioretinal dystrophies mentioned above, and hence is useful particularly for early diagnosis of these disorders.

The vestibulo-ocular reflex in fourth nerve palsy: deficits and adaptation.

PubMed

Wong, Agnes M F; Sharpe, James A; Tweed, Douglas

2002-08-01

The effects of fourth nerve palsy on the vestibulo-ocular reflex (VOR) had not been systematically investigated. We used the magnetic scleral search coil technique to study the VOR in patients with unilateral fourth nerve palsy during sinusoidal head rotations in yaw, pitch and roll at different frequencies. In darkness, VOR gains are reduced during incyclotorsion, depression and abduction of the paretic eye, as anticipated from paresis of the superior oblique muscle. VOR gains during excyclotorsion, elevation and adduction of the paretic eye are also reduced, whereas gains in the non-paretic eye remain normal, indicating a selective adjustment of innervation to the paretic eye. In light, torsional visually enhanced VOR (VVOR) gains in the paretic eye remain reduced; however, visual input increases vertical and horizontal VVOR gains to normal in the paretic eye, without a conjugate increase in VVOR gains in the non-paretic eye, providing further evidence of selective adaptation in the paretic eye. Motions of the eyes after fourth nerve palsy exemplify monocular adaptation of the VOR, in response to peripheral neuromuscular deficits.

Exogenous orienting of attention depends upon the ability to execute eye movements.

PubMed

Smith, Daniel T; Rorden, Chris; Jackson, Stephen R

2004-05-04

Shifts of attention can be made overtly by moving the eyes or covertly with attention being allocated to a region of space that does not correspond to the current direction of gaze. However, the precise relationship between eye movements and the covert orienting of attention remains controversial. The influential premotor theory proposes that the covert orienting of attention is produced by the programming of (unexecuted) eye movements and thus predicts a strong relationship between the ability to execute eye movements and the operation of spatial attention. Here, we demonstrate for the first time that impaired spatial attention is observed in an individual (AI) who is neurologically healthy but who cannot execute eye movements as a result of a congenital impairment in the elasticity of her eye muscles. This finding provides direct support for the role of the eye-movement system in the covert orienting of attention and suggests that whereas intact cortical structures may be necessary for normal attentional reflexes, they are not sufficient. The ability to move our eyes is essential for the development of normal patterns of spatial attention.

Recurrent pregnancy loss evaluation combined with 24-chromosome microarray of miscarriage tissue provides a probable or definite cause of pregnancy loss in over 90% of patients.

PubMed

Popescu, F; Jaslow, C R; Kutteh, W H

2018-04-01

Will the addition of 24-chromosome microarray analysis on miscarriage tissue combined with the standard American Society for Reproductive Medicine (ASRM) evaluation for recurrent miscarriage explain most losses? Over 90% of patients with recurrent pregnancy loss (RPL) will have a probable or definitive cause identified when combining genetic testing on miscarriage tissue with the standard ASRM evaluation for recurrent miscarriage. RPL is estimated to occur in 2-4% of reproductive age couples. A probable cause can be identified in approximately 50% of patients after an ASRM recommended workup including an evaluation for parental chromosomal abnormalities, congenital and acquired uterine anomalies, endocrine imbalances and autoimmune factors including antiphospholipid syndrome. Single-center, prospective cohort study that included 100 patients seen in a private RPL clinic from 2014 to 2017. All 100 women had two or more pregnancy losses, a complete evaluation for RPL as defined by the ASRM, and miscarriage tissue evaluated by 24-chromosome microarray analysis after their second or subsequent miscarriage. Frequencies of abnormal results for evidence-based diagnostic tests considered definite or probable causes of RPL (karyotyping for parental chromosomal abnormalities, and 24-chromosome microarray evaluation for products of conception (POC); pelvic sonohysterography, hysterosalpingogram, or hysteroscopy for uterine anomalies; immunological tests for lupus anticoagulant and anticardiolipin antibodies; and blood tests for thyroid stimulating hormone (TSH), prolactin and hemoglobin A1c) were evaluated. We excluded cases where there was maternal cell contamination of the miscarriage tissue or if the ASRM evaluation was incomplete. A cost analysis for the evaluation of RPL was conducted to determine whether a proposed procedure of 24-chromome microarray evaluation followed by an ASRM RPL workup (for those RPL patients who had a normal 24-chromosome microarray evaluation) was more cost-efficient than conducting ASRM RPL workups on RPL patients followed by 24-chromosome microarray analysis (for those RPL patients who had a normal RPL workup). A definite or probable cause of pregnancy loss was identified in the vast majority (95/100; 95%) of RPL patients when a 24-chromosome pair microarray evaluation of POC testing is combined with the standard ASRM RPL workup evaluation at the time of the second or subsequent loss. The ASRM RPL workup identified an abnormality and a probable explanation for pregnancy loss in only 45/100 or 45% of all patients. A definite abnormality was identified in 67/100 patients or 67% when initial testing was performed using 24-chromosome microarray analyses on the miscarriage tissue. Only 5/100 (5%) patients, who had a euploid loss and a normal ASRM RPL workup, had a pregnancy loss without a probable or definitive cause identified. All other losses were explained by an abnormal 24-chromosome microarray analysis of the miscarriage tissue, an abnormal finding of the RPL workup, or a combination of both. Results from the cost analysis indicated that an initial approach of using a 24-chromosome microarray analysis on miscarriage tissue resulted in a 50% savings in cost to the health care system and to the patient. This is a single-center study on a small group of well-characterized women with RPL. There was an incomplete follow-up on subsequent pregnancy outcomes after evaluation, however this should not affect our principal results. The maternal age of patients varied from 26 to 45 years old. More aneuploid pregnancy losses would be expected in older women, particularly over the age of 35 years old. Evaluation of POC using 24-chromosome microarray analysis adds significantly to the ASRM recommended evaluation of RPL. Genetic evaluation on miscarriage tissue obtained at the time of the second and subsequent pregnancy losses should be offered to all couples with two or more consecutive pregnancy losses. The combination of a genetic evaluation on miscarriage tissue with an evidence-based evaluation for RPL will identify a probable or definitive cause in over 90% of miscarriages. No funding was received for this study and there are no conflicts of interest to declare. Not applicable.

Ocular dominance in layer IV of the cat's visual cortex and the effects of monocular deprivation.

PubMed Central

Shatz, C J; Stryker, M P

1978-01-01

1. The relation between the physiological pattern of ocular dominance and the anatomical distribution of geniculocortical afferents serving each eye was studied in layer IV of the primary visual cortex of normal and monocularly deprived cats. 2. One eye was injected with radioactive label. After allowing sufficient time for transeuronal transport, micro-electrode recordings were made, and the geniculocoritcal afferents serving the injected eye were located autoradiographically. 3. In layer IV of normal cats, cell were clustered according to eye preference, and fewer cells were binocularly driven than in other layers. Points of transition between groups of cells dominated by one eye and those dominated by the other were marked with electrolytic lesions. A good correspondence was found between the location of cells dominated by the injected eye and the patches of radioactively labelled geniculocortical afferents. 4. Following prolonged early monocular deprivation, the patches of geniculocortical afferents in layer IV serving the deprived eye were smaller, and those serving the non-deprived eye larger, than normal. Again there was a coincidence between the patches of radioactively labelled afferents and the location of cells dominated by the injected eye. 5. The deprived eye was found to dominate a substantial fraction (22%) of cortical cells in the fourth layer. In other cortical layers, only 7% of the cells were dominated by the deprived eye. 6. These findings suggest that the thalamocortical projection is physically rearranged as a consequence of monocular deprivation, as has been demonstrated for layer IVc of the monkey's visual cortex (Hubel, Wiesel & Le Vay, 1977). Images Plate 1 Plate 2 Plate 3 Plate 4 Plate 5 Plate 6 PMID:702379

Therapeutic potential of Dickkopf-1 in wild-type BRAF papillary thyroid cancer via regulation of β-catenin/E-cadherin signaling.

PubMed

Cho, Sun Wook; Kim, Young A; Sun, Hyun Jin; Ahn, Hwa Young; Lee, Eun Kyung; Yi, Ka Hee; Oh, Byung-Chul; Park, Do Joon; Cho, Bo Youn; Park, Young Joo

2014-09-01

Aberrant activation of the Wnt/β-catenin pathway is a common pathogenesis of various human cancers. We investigated the role of the Wnt inhibitor, Dkk-1, in papillary thyroid cancer (PTC). Immunohistochemical β-catenin staining was performed in tissue microarray containing 148 PTCs and five normal thyroid tissues. In vivo effects of Dkk-1 were explored using ectopic tumors with BHP10-3SC cells. In 27 PTC patients, 60% of patients showed β-catenin up-regulation and Dkk-1 down-regulation in tumor vs normal tissues. Tissue microarray analysis showed that 14 of 148 PTC samples exhibited cytoplasmic-dominant β-catenin expression compared to membranous-dominant expression in normal tissues. Aberrant β-catenin expression was significantly correlated with higher rates of the loss of membranous E-cadherin expression and poor disease-free survival than that in the normal membranous expression group over a median follow-up period of 14 years. Implantation of Dkk-1-overexpressing BHP10-3SC cells revealed delayed tumor growth, resulting from the rescue of membranous β-catenin and E-cadherin expressions. Furthermore, tissue microarray analysis demonstrated that BRAF(WT) patients had higher rates of aberrant expressions of β-catenin and E-cadherin than BRAF(V600E) patients. Indeed, the inhibitory effects of Dkk-1 on cell survival were more sensitive in BRAF(WT) (BHP10-3SC and TPC-1) than in BRAF(V600E) (SNU-790 and BCPAP) cells. Overexpression of BRAF(V600E) in normal thyroid epithelial (H tori) cells also reduced the effects of Dkk-1 on cell survival. A subset of PTC patients showed aberrant expression of β-catenin/E-cadherin signaling and poor disease-free survival. Dkk-1 might have a therapeutic role, particularly in BRAF(WT) patients.

The role of visual evoked potential and electroretinography in the preoperative assessment of osteo-keratoprosthesis or osteo-odonto-keratoprosthesis surgery.

PubMed

de Araujo, Aline L; Charoenrook, Victor; de la Paz, Maria F; Temprano, Jose; Barraquer, Rafael I; Michael, Ralph

2012-09-01

To determine the value of electroretinography (ERG) and visual evoked potential (VEP) in predicting visual outcome in patients undergoing osteo-keratoprosthesis (OKP) or osteo-odonto-keratoprosthesis (OOKP) surgery. We performed a retrospective cohort study of 143 eyes in 101 patients who underwent OKP or OOKP surgery. The subjects underwent ERG, VEP testing or both up to 6 months prior to surgery. The ERG and VEP results were classified into four categories based on wave amplitude, latency and configuration. The main outcome was the maximum best-corrected visual acuity (maxBCVA) reached at any time postoperatively. One hundred thirty-four cases had undergone preoperative ERG, 82 VEP and 73 both examinations. The sensitivities of ERG and VEP to detect maxBCVA≥0.05 were 68.5% and 87%, respectively, while the specificity was 63.2% for ERG and 47.4% for VEP. The maxBCVA was significantly better in patients with normal ERG (p=0.033) and those with normal VEP (p=0.048), once having defined appropriate normal and abnormal cut-off levels. When comparing fellow eyes in patients who underwent surgery in both eyes, maxBCVA was better in the eyes that had better VEP results (p=0.013). Eyes demonstrating normal ERG or VEP achieved better visual outcome than those with abnormal results. In addition, VEP proved instrumental in determining the eye with the best prognosis when comparing both eyes of a given patient. © 2011 The Authors. Acta Ophthalmologica © 2011 Acta Ophthalmologica Scandinavica Foundation.

The Initiation of Smooth Pursuit is Delayed in Anisometropic Amblyopia.

PubMed

Raashid, Rana Arham; Liu, Ivy Ziqian; Blakeman, Alan; Goltz, Herbert C; Wong, Agnes M F

2016-04-01

Several behavioral studies have shown that the reaction times of visually guided movements are slower in people with amblyopia, particularly during amblyopic eye viewing. Here, we tested the hypothesis that the initiation of smooth pursuit eye movements, which are responsible for accurately keeping moving objects on the fovea, is delayed in people with anisometropic amblyopia. Eleven participants with anisometropic amblyopia and 14 visually normal observers were asked to track a step-ramp target moving at ±15°/s horizontally as quickly and as accurately as possible. The experiment was conducted under three viewing conditions: amblyopic/nondominant eye, binocular, and fellow/dominant eye viewing. Outcome measures were smooth pursuit latency, open-loop gain, steady state gain, and catch-up saccade frequency. Participants with anisometropic amblyopia initiated smooth pursuit significantly slower during amblyopic eye viewing (206 ± 20 ms) than visually normal observers viewing with their nondominant eye (183 ± 17 ms, P = 0.002). However, mean pursuit latency in the anisometropic amblyopia group during binocular and monocular fellow eye viewing was comparable to the visually normal group. Mean open-loop gain, steady state gain, and catch-up saccade frequency were similar between the two groups, but participants with anisometropic amblyopia exhibited more variable steady state gain (P = 0.045). This study provides evidence of temporally delayed smooth pursuit initiation in anisometropic amblyopia. After initiation, the smooth pursuit velocity profile in anisometropic amblyopia participants is similar to visually normal controls. This finding differs from what has been observed previously in participants with strabismic amblyopia who exhibit reduced smooth pursuit velocity gains with more catch-up saccades.

Vergence-mediated changes in the axis of eye rotation during the human vestibulo-ocular reflex can occur independent of eye position.

PubMed

Migliaccio, Americo A; Cremer, Phillip D; Aw, Swee T; Halmagyi, G Michael; Curthoys, Ian S; Minor, Lloyd B; Todd, Michael J

2003-07-01

The aim of this study was to determine whether vergence-mediated changes in the axis of eye rotation in the human vestibulo-ocular reflex (VOR) would obey Listing's Law (normally associated with saccadic eye movements) independent of the initial eye position. We devised a paradigm for disassociating the saccadic velocity axis from eye position by presenting near and far targets that were centered with respect to one eye. We measured binocular 3-dimensional eye movements using search coils in ten normal subjects and 3-dimensional linear head acceleration using Optotrak in seven normal subjects. The stimuli consisted of passive, unpredictable, pitch head rotations with peak acceleration of approximately 2000 degrees /s(2 )and amplitude of approximately 20 degrees. During the pitch head rotation, each subject fixated straight ahead with one eye, whereas the other eye was adducted 4 degrees during far viewing (94 cm) and 25 degrees during near viewing (15 cm). Our data showed expected compensatory pitch rotations in both eyes, and a vergence-mediated horizontal rotation only in the adducting eye. In addition, during near viewing we observed torsional eye rotations not only in the adducting eye but also in the eye looking straight ahead. In the straight-ahead eye, the change in torsional eye velocity between near and far viewing, which began approximately 40 ms after the start of head rotation, was 10+/-6 degrees /s (mean +/- SD). This change in torsional eye velocity resulted in a 2.4+/-1.5 degrees axis tilt toward Listing's plane in that eye. In the adducting eye, the change in torsional eye velocity between near and far viewing was 16+/-6 degrees /s (mean +/- SD) and resulted in a 4.1+/-1.4 degrees axis tilt. The torsional eye velocities were conjugate and both eyes partially obeyed Listing's Law. The axis of eye rotation tilted in the direction of the line of sight by approximately one-third of the angle between the line of sight and a line orthogonal to Listing's plane. This tilt was higher than predicted by the one-quarter rule. The translational acceleration component of the pitch head rotation measured 0.5 g and may have contributed to the increased torsional component observed during near viewing. Our data show that vergence-mediated eye movements obey a VOR/Listing's Law compromise strategy independent of the initial eye position.

[Expression of cell adhesion molecules in acute leukemia cell].

PubMed

Ju, Xiaoping; Peng, Min; Xu, Xiaoping; Lu, Shuqing; Li, Yao; Ying, Kang; Xie, Yi; Mao, Yumin; Xia, Fang

2002-11-01

To investigate the role of cell adhesion molecule in the development and extramedullary infiltration (EI) of acute leukemia. The expressions of neural cell adhesion molecule (NCAM) gene, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule (VCAM-1) genes in 25 acute leukemia patients bone marrow cells were detected by microarray and reverse transcriptase-polymerase chain reaction (RT-PCR). The expressions of NCAM, ICAM-1 and VCAM-1 gene were significantly higher in acute leukemia cells and leukemia cells with EI than in normal tissues and leukemia cells without EI, respectively, both by cDNA microarray and by RT-PCR. The cDNA microarray is a powerful technique in analysis of acute leukemia cells associated genes. High expressions of cell adhesion molecule genes might be correlated with leukemia pathogenesis and infiltration of acute leukemia cell.

Mycoplasma and associated bacteria isolated from ovine pink-eye.

PubMed

Langford, E V

1971-01-01

A mycoplasma was recovered from the untreated conjunctival membranes of nine sheep affected by Pink-eye. It was neither isolated from the conjunctiva of treated animals which were affected nor from the conjunctiva of normal animals either in contact or not in contact with affected animals. Bacteria found on normal conjunctival membranes were Neisseria ovis, Escherichia coli, Staphylococcus epidermididis, Streptococcus and Bacillus spp. Bacteria found in clinical cases of Pink-eye were N. ovis, E. coli, a Streptococcus and Pseudomonas spp.

Gene expression profiling of two distinct neuronal populations in the rodent spinal cord.

PubMed

Ryge, Jesper; Westerdahl, Ann-Charlotte; Alstrøm, Preben; Kiehn, Ole

2008-01-01

In the field of neuroscience microarray gene expression profiles on anatomically defined brain structures are being used increasingly to study both normal brain functions as well as pathological states. Fluorescent tracing techniques in brain tissue that identifies distinct neuronal populations can in combination with global gene expression profiling potentially increase the resolution and specificity of such studies to shed new light on neuronal functions at the cellular level. We examine the microarray gene expression profiles of two distinct neuronal populations in the spinal cord of the neonatal rat, the principal motor neurons and specific interneurons involved in motor control. The gene expression profiles of the respective cell populations were obtained from amplified mRNA originating from 50-250 fluorescently identified and laser microdissected cells. In the data analysis we combine a new microarray normalization procedure with a conglomerate measure of significant differential gene expression. Using our methodology we find 32 genes to be more expressed in the interneurons compared to the motor neurons that all except one have not previously been associated with this neuronal population. As a validation of our method we find 17 genes to be more expressed in the motor neurons than in the interneurons and of these only one had not previously been described in this population. We provide an optimized experimental protocol that allows isolation of gene transcripts from fluorescent retrogradely labeled cell populations in fresh tissue, which can be used to generate amplified aRNA for microarray hybridization from as few as 50 laser microdissected cells. Using this optimized experimental protocol in combination with our microarray analysis methodology we find 49 differentially expressed genes between the motor neurons and the interneurons that reflect the functional differences between these two cell populations in generating and transmitting the motor output in the rodent spinal cord.

Gene Expression Profiling of Two Distinct Neuronal Populations in the Rodent Spinal Cord

PubMed Central

Alstrøm, Preben; Kiehn, Ole

2008-01-01

Background In the field of neuroscience microarray gene expression profiles on anatomically defined brain structures are being used increasingly to study both normal brain functions as well as pathological states. Fluorescent tracing techniques in brain tissue that identifies distinct neuronal populations can in combination with global gene expression profiling potentially increase the resolution and specificity of such studies to shed new light on neuronal functions at the cellular level. Methodology/Principal Findings We examine the microarray gene expression profiles of two distinct neuronal populations in the spinal cord of the neonatal rat, the principal motor neurons and specific interneurons involved in motor control. The gene expression profiles of the respective cell populations were obtained from amplified mRNA originating from 50–250 fluorescently identified and laser microdissected cells. In the data analysis we combine a new microarray normalization procedure with a conglomerate measure of significant differential gene expression. Using our methodology we find 32 genes to be more expressed in the interneurons compared to the motor neurons that all except one have not previously been associated with this neuronal population. As a validation of our method we find 17 genes to be more expressed in the motor neurons than in the interneurons and of these only one had not previously been described in this population. Conclusions/Significance We provide an optimized experimental protocol that allows isolation of gene transcripts from fluorescent retrogradely labeled cell populations in fresh tissue, which can be used to generate amplified aRNA for microarray hybridization from as few as 50 laser microdissected cells. Using this optimized experimental protocol in combination with our microarray analysis methodology we find 49 differentially expressed genes between the motor neurons and the interneurons that reflect the functional differences between these two cell populations in generating and transmitting the motor output in the rodent spinal cord. PMID:18923679

A Customized DNA Microarray for Microbial Source Tracking ...

EPA Pesticide Factsheets

It is estimated that more than 160, 000 miles of rivers and streams in the United States are impaired due to the presence of waterborne pathogens. These pathogens typically originate from human and other animal fecal pollution sources; therefore, a rapid microbial source tracking (MST) method is needed to facilitate water quality assessment and impaired water remediation. We report a novel qualitative DNA microarray technology consisting of 453 probes for the detection of general fecal and host-associated bacteria, viruses, antibiotic resistance, and other environmentally relevant genetic indicators. A novel data normalization and reduction approach is also presented to help alleviate false positives often associated with high-density microarray applications. To evaluate the performance of the approach, DNA and cDNA was isolated from swine, cattle, duck, goose and gull fecal reference samples, as well as soiled poultry liter and raw municipal sewage. Based on nonmetric multidimensional scaling analysis of results, findings suggest that the novel microarray approach may be useful for pathogen detection and identification of fecal contamination in recreational waters. The ability to simultaneously detect a large collection of environmentally important genetic indicators in a single test has the potential to provide water quality managers with a wide range of information in a short period of time. Future research is warranted to measure microarray performance i

Protein microarray analysis reveals BAFF-binding autoantibodies in systemic lupus erythematosus

PubMed Central

Price, Jordan V.; Haddon, David J.; Kemmer, Dodge; Delepine, Guillaume; Mandelbaum, Gil; Jarrell, Justin A.; Gupta, Rohit; Balboni, Imelda; Chakravarty, Eliza F.; Sokolove, Jeremy; Shum, Anthony K.; Anderson, Mark S.; Cheng, Mickie H.; Robinson, William H.; Browne, Sarah K.; Holland, Steven M.; Baechler, Emily C.; Utz, Paul J.

2013-01-01

Autoantibodies against cytokines, chemokines, and growth factors inhibit normal immunity and are implicated in inflammatory autoimmune disease and diseases of immune deficiency. In an effort to evaluate serum from autoimmune and immunodeficient patients for Abs against cytokines, chemokines, and growth factors in a high-throughput and unbiased manner, we constructed a multiplex protein microarray for detection of serum factor–binding Abs and used the microarray to detect autoantibody targets in SLE. We designed a nitrocellulose-surface microarray containing human cytokines, chemokines, and other circulating proteins and demonstrated that the array permitted specific detection of serum factor–binding probes. We used the arrays to detect previously described autoantibodies against cytokines in samples from individuals with autoimmune polyendocrine syndrome type 1 and chronic mycobacterial infection. Serum profiling from individuals with SLE revealed that among several targets, elevated IgG autoantibody reactivity to B cell–activating factor (BAFF) was associated with SLE compared with control samples. BAFF reactivity correlated with the severity of disease-associated features, including IFN-α–driven SLE pathology. Our results showed that serum factor protein microarrays facilitate detection of autoantibody reactivity to serum factors in human samples and that BAFF-reactive autoantibodies may be associated with an elevated inflammatory disease state within the spectrum of SLE. PMID:24270423

Quantitative analysis of iris changes after physiologic and pharmacologic mydriasis in a rural Chinese population.

PubMed

Zhang, Ye; Li, Si Zhen; Li, Lei; He, Ming Guang; Thomas, Ravi; Wang, Ning Li

2014-04-24

To estimate and compare the change in iris cross-sectional area (IA) and iris volume (IV) following physiologic and pharmacologic pupil dilation in primary angle closure suspects (PACS) and normal subjects. Anterior segment-optical coherence tomography (AS-OCT) measurements in light, dark, and following pharmacologic dilation were obtained on 186 PACS and 224 normal subjects examined during the 5-year follow-up of the Handan Eye Study. Iris cross-sectional area, IV, and other biometric parameters calculated using the Zhongshan angle assessment program in the right eyes of all subjects were analyzed. The mean IA and IV decreased in dark compared with light and after pharmacologic dilation in both PACS and normal eyes. This change was statistically significant in normal eyes: light versus pharmacologic dilation for IA (P = 0.038) and for IV, both light versus dark (P = 0.031) and light versus pharmacologic dilation (P = 0.012). A longer axial length (P = 0.028) and a greater change in pupil diameter (PD) (P < 0.001) were associated with a larger decrease of IA for the light to dark comparison. A diagnosis of normal eyes (P = 0.011), larger PD in dark (P = 0.001), and a larger change in PD (P = 0.001) were associated with a larger decrease of IV from light to dark. The differences in iris behavior between PACS and normal rural Chinese subjects following physiologic or pharmacologic pupillary dilation may help provide insights into the pathogenesis of angle closure. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

Sensory Eye Dominance in Treated Anisometropic Amblyopia

PubMed Central

Chen, Yao

2017-01-01

Amblyopia results from inadequate visual experience during the critical period of visual development. Abnormal binocular interactions are believed to play a critical role in amblyopia. These binocular deficits can often be resolved, owing to the residual visual plasticity in amblyopes. In this study, we quantitatively measured the sensory eye dominance in treated anisometropic amblyopes to determine whether they had fully recovered. Fourteen treated anisometropic amblyopes with normal or corrected to normal visual acuity participated, and their sensory eye dominance was assessed by using a binocular phase combination paradigm. We found that the two eyes were unequal in binocular combination in most (11 out of 14) of our treated anisometropic amblyopes, but none of the controls. We concluded that the treated anisometropic amblyopes, even those with a normal range of visual acuity, exhibited abnormal binocular processing. Our results thus suggest that there is potential for improvement in treated anisometropic amblyopes that may further enhance their binocular visual functioning. PMID:28573051

Ultrasonography of the eye and orbit.

PubMed

Eisenberg, H M

1985-11-01

The eye and orbit are excellent subjects for ultrasonic evaluation. Examination and interpretation are relatively simple procedures. The normal ultrasonic anatomy of the eye and orbit is presented. Some examples of ocular and orbital pathology are discussed also.

A Multidisciplinary Approach for Rehabilitation of Enucleated Sockets: Ocular Implants with Custom Ocular Prosthesis.

PubMed

Choudhury, Minati; Banu, Fathima; Natarajan, Shanmuganathan; Kumar, Anand; Tv, Padmanabhan

2018-02-16

Interdisciplinary prosthodontics goes beyond our imagination into fields that have a direct effect on our total body health and quality of life. Removal of an eye has a detrimental effect on the psychology of the patient. Enucleation involves removal of the eyeball proper and leads to an enophthalmic socket with a shrunken eye, which has a crippling effect on patient's emotional and social life. Custom-made eye prosthesis simulates the characteristics of the companion eye and helps in restoring the normal facial appearance. Restoration of saccadic eye movements occurring during speech is desirable because this greatly contributes to a normal facial expression. This can be achieved by an orbital implant, which helps in orbital volume replacement and restoration of prosthesis movement and comfort. This article describes prosthodontic rehabilitation of enucleated eye sockets with orbital implants for two patients.

Adaptable gene-specific dye bias correction for two-channel DNA microarrays.

PubMed

Margaritis, Thanasis; Lijnzaad, Philip; van Leenen, Dik; Bouwmeester, Diane; Kemmeren, Patrick; van Hooff, Sander R; Holstege, Frank C P

2009-01-01

DNA microarray technology is a powerful tool for monitoring gene expression or for finding the location of DNA-bound proteins. DNA microarrays can suffer from gene-specific dye bias (GSDB), causing some probes to be affected more by the dye than by the sample. This results in large measurement errors, which vary considerably for different probes and also across different hybridizations. GSDB is not corrected by conventional normalization and has been difficult to address systematically because of its variance. We show that GSDB is influenced by label incorporation efficiency, explaining the variation of GSDB across different hybridizations. A correction method (Gene- And Slide-Specific Correction, GASSCO) is presented, whereby sequence-specific corrections are modulated by the overall bias of individual hybridizations. GASSCO outperforms earlier methods and works well on a variety of publically available datasets covering a range of platforms, organisms and applications, including ChIP on chip. A sequence-based model is also presented, which predicts which probes will suffer most from GSDB, useful for microarray probe design and correction of individual hybridizations. Software implementing the method is publicly available.

Adaptable gene-specific dye bias correction for two-channel DNA microarrays

PubMed Central

Margaritis, Thanasis; Lijnzaad, Philip; van Leenen, Dik; Bouwmeester, Diane; Kemmeren, Patrick; van Hooff, Sander R; Holstege, Frank CP

2009-01-01

DNA microarray technology is a powerful tool for monitoring gene expression or for finding the location of DNA-bound proteins. DNA microarrays can suffer from gene-specific dye bias (GSDB), causing some probes to be affected more by the dye than by the sample. This results in large measurement errors, which vary considerably for different probes and also across different hybridizations. GSDB is not corrected by conventional normalization and has been difficult to address systematically because of its variance. We show that GSDB is influenced by label incorporation efficiency, explaining the variation of GSDB across different hybridizations. A correction method (Gene- And Slide-Specific Correction, GASSCO) is presented, whereby sequence-specific corrections are modulated by the overall bias of individual hybridizations. GASSCO outperforms earlier methods and works well on a variety of publically available datasets covering a range of platforms, organisms and applications, including ChIP on chip. A sequence-based model is also presented, which predicts which probes will suffer most from GSDB, useful for microarray probe design and correction of individual hybridizations. Software implementing the method is publicly available. PMID:19401678

Laser speckle flowgraphy for differentiating between nonarteritic ischemic optic neuropathy and anterior optic neuritis.

PubMed

Maekubo, Tomoyuki; Chuman, Hideki; Nao-I, Nobuhisa

2013-07-01

The aim of this study was to investigate the usefulness of laser speckle flowgraphy (LSFG) for the differentiation of acute nonarteritic ischemic optic neuropathy (NAION) from anterior optic neuritis (ON). To investigate blood flow in the optic disc under normal conditions, NAION, and anterior ON, we compared the tissue blood flow of the right eye with that of the left eye in the control group, and that of the affected eye with that of the unaffected eye in the NAION and anterior ON groups. In the normal control group, the tissue blood flow did not significantly differ between the right and left eyes. In the NAION group, all 6 patients had decreased optic disc blood flow in the NAION eye when compared with the unaffected eye. By contrast, in the anterior ON group, all 6 patients had increased optic disc blood flow in the anterior ON eye when compared with the unaffected eye. In the NAION group, the mean blur rate (MBR) of the affected eyes was 29.5 % lower than that of the unaffected eyes. In the anterior ON group, the MBR of the affected eyes was 15.9 % higher than that of the unaffected eyes. LSFG could be useful in differentiating between NAION and anterior ON. In addition, this imaging technique saves time and is noninvasive.

New screening methods for donor eye-bank eyes.

PubMed

Terry, M A; Ousley, P J

1999-07-01

Current methods of screening donor eyes for corneal transplantation are not always effective in excluding corneas with abnormal topography. We used the Orbscan to determine whether corneal-thickness maps could be used as a technique for donor tissue screening. Forty eye-bank eyes were measured with the Orbscan, and a corneal-thickness map was generated. Average central pachymetry measurements from each map were compared with the thinnest midperipheral thickness reading. Two eyes from a donor who had photorefractive keratectomy (PRK) and two eyes from a donor with keratoconus were then compared with the normal donor eye results. The average difference between the thinnest midperipheral pachymetry and the central pachymetry in the control group was 0.040 +/- 0.026 mm. The eyes from the donor with PRK showed larger disparities between the central and midperipheral thicknesses because of the thinned central cornea, with differences of 0.154 mm in the right eye and 0.106 mm in the left eye. The eyes from the donor with keratoconus had midperipheral corneas that were thinner than the center, indicating eccentric, ectatic cones. The differences in thickness between the center and midperiphery in the eyes from the donor with PRK and the donor with keratoconus differed from the control group by >2 SD. Diseases or surgery that affect the relationship between the central and midperipheral corneal thickness may be screened through Orbscan pachymetry mapping with comparison with a normal range.

Comparative Study of Anterior Eye Segment Measurements with Spectral Swept-Source and Time-Domain Optical Coherence Tomography in Eyes with Corneal Dystrophies

PubMed Central

Teper, Sławomir J.; Janiszewska, Dominika A.; Lyssek-Boron, Anita; Dobrowolski, Dariusz; Koprowski, Robert; Wylegala, Edward

2015-01-01

Purpose. To compare anterior eye segment measurements and morphology obtained with two optical coherence tomography systems (TD OCT, SS OCT) in eyes with corneal dystrophies (CDs). Methods. Fifty healthy volunteers (50 eyes) and 54 patients (96 eyes) diagnosed with CD (epithelial basement membrane dystrophy, EBMD = 12 eyes; Thiel-Behnke CD = 6 eyes; lattice CD TGFBI type = 15 eyes; granular CD type 1 = 7 eyes, granular CD type 2 = 2 eyes; macular CD = 23 eyes; and Fuchs endothelial CD = 31 eyes) were recruited for the study. Automated and manual central corneal thickness (aCCT, mCCT), anterior chamber depth (ACD), and nasal and temporal trabecular iris angle (nTIA, tTIA) were measured and compared with Bland-Altman plots. Results. Good agreement between the TD and SS OCT measurements was demonstrated for mCCT and aCCT in normal individuals and for mCCT in the CDs group. The ACD, nTIA, and tTIA measurements differed significantly in both groups. TBCD, LCD, and FECD caused increased CCT. MCD caused significant corneal thinning. FECD affected all analyzed parameters. Conclusions. Better agreement between SS OCT and TD OCT measurements was demonstrated in normal individuals compared to the CDs group. OCT provides comprehensive corneal deposits analysis and demonstrates the association of CD with CCT, ACD, and TIA measurements. PMID:26457303

Comparative Study of Anterior Eye Segment Measurements with Spectral Swept-Source and Time-Domain Optical Coherence Tomography in Eyes with Corneal Dystrophies.

PubMed

Nowinska, Anna K; Teper, Sławomir J; Janiszewska, Dominika A; Lyssek-Boron, Anita; Dobrowolski, Dariusz; Koprowski, Robert; Wylegala, Edward

2015-01-01

To compare anterior eye segment measurements and morphology obtained with two optical coherence tomography systems (TD OCT, SS OCT) in eyes with corneal dystrophies (CDs). Fifty healthy volunteers (50 eyes) and 54 patients (96 eyes) diagnosed with CD (epithelial basement membrane dystrophy, EBMD = 12 eyes; Thiel-Behnke CD = 6 eyes; lattice CD TGFBI type = 15 eyes; granular CD type 1 = 7 eyes, granular CD type 2 = 2 eyes; macular CD = 23 eyes; and Fuchs endothelial CD = 31 eyes) were recruited for the study. Automated and manual central corneal thickness (aCCT, mCCT), anterior chamber depth (ACD), and nasal and temporal trabecular iris angle (nTIA, tTIA) were measured and compared with Bland-Altman plots. Good agreement between the TD and SS OCT measurements was demonstrated for mCCT and aCCT in normal individuals and for mCCT in the CDs group. The ACD, nTIA, and tTIA measurements differed significantly in both groups. TBCD, LCD, and FECD caused increased CCT. MCD caused significant corneal thinning. FECD affected all analyzed parameters. Better agreement between SS OCT and TD OCT measurements was demonstrated in normal individuals compared to the CDs group. OCT provides comprehensive corneal deposits analysis and demonstrates the association of CD with CCT, ACD, and TIA measurements.

Biomechanical Changes in the Sclera of Monkey Eyes Exposed to Chronic IOP Elevations

PubMed Central

Girard, Michaël J. A.; Suh, J.-K. Francis; Bottlang, Michael; Burgoyne, Claude F.

2011-01-01

Purpose. To characterize scleral biomechanics in both eyes of eight monkeys in which chronic intraocular pressure (IOP) elevation was induced in one eye. Methods. Each posterior sclera was mounted on a pressurization apparatus, IOP was elevated from 5 to 45 mm Hg while the 3D displacements of the scleral surface were measured by speckle interferometry. Finite element (FE) models of each scleral shell were constructed that incorporated stretch-induced stiffening and multidirectionality of the collagen fibers. FE model predictions were then iteratively matched to experimental displacements to extract unique sets of scleral biomechanical properties. Results. For all eyes, the posterior sclera exhibited inhomogeneous, anisotropic, nonlinear biomechanical behavior. Biomechanical changes caused by chronic IOP elevation were complex and specific to each subject. Specifically: (1) Glaucomatous eyes in which the contralateral normal eyes displayed large modulus or thickness were less prone to biomechanical changes; (2) glaucomatous scleral modulus associated with an IOP of 10 mm Hg decreased (when compared with that of the contralateral normal) after minimal chronic IOP elevation; (3) glaucomatous scleral modulus associated with IOPs of 30 and 45 mm Hg increased (when compared with that of the contralateral normal) after moderate IOP elevation; and (4) FE-based estimates of collagen fiber orientation demonstrated no change in the glaucomatous eyes. Conclusions. Significant stiffening of the sclera follows exposure to moderate IOP elevations in most eyes. Scleral hypercompliance may precede stiffening or be a unique response to minimal chronic IOP elevation in some eyes. These biomechanical changes are likely to be the result of scleral extracellular matrix remodeling. PMID:21519033

Comparison of glaucoma diagnostic accuracy of macular ganglion cell complex thickness based on nonhighly myopic and highly myopic normative database

PubMed Central

Chen, Henry Shen-Lih; Liu, Chun-Hsiu; Lu, Da-Wen

2016-01-01

Background/Purpose: To evaluate and compare the diagnostic discriminative ability for detecting glaucoma in highly myopic eyes from a normative database of macular ganglion cell complex (mGCC) thickness based on nonhighly myopic and highly myopic normal eyes. Methods: Forty-nine eyes of 49 participants with high myopia (axial length ≥ 26.0 mm) were enrolled. Spectral-domain optical coherence tomography scans were done using RS-3000, and the mGCC thickness/significance maps within a 9-mm diameter circle were generated using built-in software. We compared the difference of sensitivity, specificity, and diagnostic accuracy between the nonhighly myopic database and the highly myopic database for differentiating the early glaucomatous eyes from the nonglaucomatous eyes. Results: This study enrolled 15 normal eyes and 34 eyes with glaucoma. The mean mGCC thickness of the glaucoma group was significantly less than that of the normal group (p < 0.001). Sensitivity was 96.3%, and the specificity was 50.0% when using the nonhighly myopic normative database. When the highly myopic normative database was used, the sensitivity was 88.9%, and the specificity was 90.0%. The false positive rate was significantly lower when using the highly myopic normative database (p < 0.05). Conclusion: The evaluations of glaucoma in eyes with high myopia using a nonhighly myopic normative database may lead to a frequent misdiagnosis. When evaluating glaucoma in high myopic eyes, the mGCC thickness determined by the long axial length high myopic normative database should be applied. PMID:29018704

The Cerebellar Dysplasia of Chiari II Malformation as Revealed by Eye Movements

PubMed Central

Salman, Michael S.; Dennis, Maureen; Sharpe, James A.

2011-01-01

Introduction Chiari type II malformation (CII) is a developmental deformity of the hindbrain. We have previously reported that many patients with CII have impaired smooth pursuit, while few make inaccurate saccades or have an abnormal vestibulo-ocular reflex. In contrast, saccadic adaptation and visual fixation are normal. In this report, we correlate results from several eye movement studies with neuroimaging in CII. We present a model for structural changes within the cerebellum in CII. Methods Saccades, smooth pursuit, the vestibulo-ocular reflex, and visual fixation were recorded in 21 patients with CII, aged 8–19 years and 39 age-matched controls, using an infrared eye tracker. Qualitative and quantitative MRI data were correlated with eye movements in 19 CII patients and 28 controls. Results Nine patients with CII had abnormal eye movements. Smooth pursuit gain was subnormal in eight, saccadic accuracy abnormal in four, and vestibulo-ocular reflex gain abnormal in three. None had fixation instability. Patients with CII had a significantly smaller cerebellar volume than controls, and those with normal eye motion had an expanded midsagittal vermis compared to controls. However, patients with abnormal eye movements had a smaller (non-expanded) midsagittal vermis area, posterior fossa area and medial cerebellar volumes than CII patients with normal eye movements. Conclusions The deformity of CII affects the structure and function of the cerebellum selectively and differently in those with abnormal eye movements. We propose that the vermis can expand when compressed within a small posterior fossa in some CII patients, thus sparing its ocular motor functions. PMID:19960749

Cone structure imaged with adaptive optics scanning laser ophthalmoscopy in eyes with nonneovascular age-related macular degeneration.

PubMed

Zayit-Soudry, Shiri; Duncan, Jacque L; Syed, Reema; Menghini, Moreno; Roorda, Austin J

2013-11-15

To evaluate cone spacing using adaptive optics scanning laser ophthalmoscopy (AOSLO) in eyes with nonneovascular AMD, and to correlate progression of AOSLO-derived cone measures with standard measures of macular structure. Adaptive optics scanning laser ophthalmoscopy images were obtained over 12 to 21 months from seven patients with AMD including four eyes with geographic atrophy (GA) and four eyes with drusen. Adaptive optics scanning laser ophthalmoscopy images were overlaid with color, infrared, and autofluorescence fundus photographs and spectral domain optical coherence tomography (SD-OCT) images to allow direct correlation of cone parameters with macular structure. Cone spacing was measured for each visit in selected regions including areas over drusen (n = 29), at GA margins (n = 14), and regions without drusen or GA (n = 13) and compared with normal, age-similar values. Adaptive optics scanning laser ophthalmoscopy imaging revealed continuous cone mosaics up to the GA edge and overlying drusen, although reduced cone reflectivity often resulted in hyporeflective AOSLO signals at these locations. Baseline cone spacing measures were normal in 13/13 unaffected regions, 26/28 drusen regions, and 12/14 GA margin regions. Although standard clinical measures showed progression of GA in all study eyes, cone spacing remained within normal ranges in most drusen regions and all GA margin regions. Adaptive optics scanning laser ophthalmoscopy provides adequate resolution for quantitative measurement of cone spacing at the margin of GA and over drusen in eyes with AMD. Although cone spacing was often normal at baseline and remained normal over time, these regions showed focal areas of decreased cone reflectivity. These findings may provide insight into the pathophysiology of AMD progression. (ClinicalTrials.gov number, NCT00254605).

Cone Integrity in Glaucoma: An Adaptive-Optics Scanning Laser Ophthalmoscopy Study.

PubMed

Hasegawa, Tomoko; Ooto, Sotaro; Takayama, Kohei; Makiyama, Yukiko; Akagi, Tadamichi; Ikeda, Hanako O; Nakanishi, Hideo; Suda, Kenji; Yamada, Hiroshi; Uji, Akihito; Yoshimura, Nagahisa

2016-11-01

To investigate photoreceptor changes in eyes with glaucoma. Cross-sectional study. The study included 35 eyes of 35 patients with primary open-angle glaucoma who had suffered parafoveal visual field loss at least 3 years previously, as well as 21 eyes of 21 normal subjects. Eyes with an axial length ≥26.0 mm were excluded. All subjects underwent a full ophthalmologic examination, including spectral-domain optical coherence tomography (SDOCT) and prototype adaptive-optics scanning laser ophthalmoscopy (AO-SLO) imaging. As determined using AO-SLO, eyes with glaucoma did not differ significantly from normal eyes in terms of either cone density (26 468 ± 3392 cones/m 2 vs 26 147 ± 2700 cones/m 2 , respectively; P = .77; measured 0.5 mm from the foveal center) or cone spatial organization (ratio of hexagonal Voronoi domain: 43.7% ± 4.4% vs 44.3% ± 4.9%; P = .76; measured 0.5 mm from the foveal center). Furthermore, SDOCT showed that the 2 groups did not differ significantly in terms of the photoreceptor-related layer thickness, and that the photoreceptor ellipsoid zone band was continuous in all normal and glaucoma eyes. In glaucoma eyes with vertically asymmetric severity, the more affected side did not significantly differ from the less affected side in terms of cone density, cone spatial organization, or photoreceptor-related layer thickness. In 8 eyes (22.9%) with glaucoma, dark, partition-like areas surrounded the cones on the AO-SLO. Both AO-SLO and SDOCT showed cone integrity in eyes with glaucoma, even in areas with visual field and nerve fiber loss. In AO-SLO, microcystic lesions in the inner nuclear layer may influence images of the cone mosaic. Copyright © 2016 Elsevier Inc. All rights reserved.

"If it helps..." the use of microarray technology in prenatal testing: patient and partners reflections.

PubMed

Hillman, Sarah C; Skelton, John; Quinlan-Jones, Elizabeth; Wilson, Amie; Kilby, Mark D

2013-07-01

The objective was to gain insight into the experiences of women and their partners diagnosed with a fetal abnormality on prenatal ultrasound examination and receiving genetic testing including microarray. Twenty-five semi-structured interviews were performed with women +/- their partners after receiving the results of prenatal genetic testing. Framework analysis was performed to elicit themes and subthemes. Five main themes were recognized; diagnosis, genetic testing, family and support, reflections of the treatment received and emotions. Our results showed that women recall being told about QFPCR for trisomy 13, 18, and 21 but often no further testing. Women expected the conventional karyotype and microarray result would be normal following a normal QFPCR result. There were frequent misconceptions by couples regarding aspects of counseling/testing. Communication of variants of unknown (clinical) significance (VOUS) presents a particularly difficult challenge. Good clear communication by health care professionals is paramount. When counseling women and their partners for fetal chromosomal testing it should be reinforced that although the most common, trisomy 13, 18, and 21 only account for some of the chromosomal changes resulting in abnormal scan findings. Couples should have literature to take home summarizing scan anomalies and reinforcing information about genetic testing. Copyright © 2013 Wiley Periodicals, Inc.

[DNA microarray reveals changes in gene expression of endothelial cells under shear stress].

PubMed

Cheng, Min; Zhang, Wensheng; Chen, Huaiqing; Wu, Wenchao; Huang, Hua

2004-04-01

cDNA microarray technology is used as a powerful tool for rapid, comprehensive, and quantitative analysis of gene profiles of cultured human umbilical vein endothelial cells(HUVECs) in the normal static group and the shear stressed (4.20 dyne/cm2, 2 h) group. The total RNA from normal static cultured HUVECs was labeled by Cy3-dCTP, and total RNA of HUVECs from the paired shear stressed experiment was labeled by Cy5-dCTP. The expression ratios reported are the average from the two separate experiments. After bioinformatics analysis, we identified a total of 108 genes (approximately 0.026%) revealing differential expression. Of these 53 genes expressions were up-regulated, the most enhanced ones being human homolog of yeast IPP isomerase, human low density lipoprotein receptor gene, Squalene epoxidase gene, 7-dehydrocholesterol reductase, and 55 were down-regulated, the most decreased ones being heat shock 70 kD protein 1, TCB gene encoding cytosolic thyroid hormone-binding protein in HUVECs exposed to low shear stress. These results indicate that the cDNA microarray technique is effective in screening the differentially expressed genes in endothelial cells induced by various experimental conditions and the data may serve as stimuli to further researches.

3D modeling to characterize lamina cribrosa surface and pore geometries using in vivo images from normal and glaucomatous eyes

PubMed Central

Sredar, Nripun; Ivers, Kevin M.; Queener, Hope M.; Zouridakis, George; Porter, Jason

2013-01-01

En face adaptive optics scanning laser ophthalmoscope (AOSLO) images of the anterior lamina cribrosa surface (ALCS) represent a 2D projected view of a 3D laminar surface. Using spectral domain optical coherence tomography images acquired in living monkey eyes, a thin plate spline was used to model the ALCS in 3D. The 2D AOSLO images were registered and projected onto the 3D surface that was then tessellated into a triangular mesh to characterize differences in pore geometry between 2D and 3D images. Following 3D transformation of the anterior laminar surface in 11 normal eyes, mean pore area increased by 5.1 ± 2.0% with a minimal change in pore elongation (mean change = 0.0 ± 0.2%). These small changes were due to the relatively flat laminar surfaces inherent in normal eyes (mean radius of curvature = 3.0 ± 0.5 mm). The mean increase in pore area was larger following 3D transformation in 4 glaucomatous eyes (16.2 ± 6.0%) due to their more steeply curved laminar surfaces (mean radius of curvature = 1.3 ± 0.1 mm), while the change in pore elongation was comparable to that in normal eyes (−0.2 ± 2.0%). This 3D transformation and tessellation method can be used to better characterize and track 3D changes in laminar pore and surface geometries in glaucoma. PMID:23847739

Effect of Intravenous Mannitol on Intraocular Pressure in Vitrectomized Silicone-Oil-Filled Eyes.

PubMed

Takkar, Brijesh; Chandra, Parijat; Shah, Ritu; Bhatia, Indrish; Roy, Sangeeta; Sihota, Ramanjit

2017-01-01

To evaluate the effect of intravenous mannitol (IVM) on intraocular pressure (IOP) in vitrectomized eyes. Thirty-one patients with raised IOP after retinal surgery with silicone oil injection were included. Patients were administered IVM (20% solution, 1g/Kg, over 30 minutes) and IOP was noted at regular intervals. IOP reduction in vitrectomized eyes (Group 1) was compared with the normal eyes (Group 2). Percentage IOP reduction was higher in Group 1 than in Group 2 at all time intervals, 24.5% vs. 19.2% at 15 minutes (p=0.34), 22.6% vs. 9.8% at 45 minutes (p=0.003), 19.1% vs. 9.9% at two hours (p=0.023), and 16.1% vs. 7.8% at four hours (p=0.04), respectively. In Group 1, 40% eyes had an IOP reduction of 2-6 mmHg while 30% eyes had IOP reduction >6 mmHg at four hours post-IVM. IVM is useful for short-term IOP reduction in vitrectomized eyes. IOP reduction is independent of baseline IOP, and sustained and higher as compared to normal eyes.

Tear proteomic analysis of patients with type 2 diabetes and dry eye syndrome by two-dimensional nano-liquid chromatography coupled with tandem mass spectrometry.

PubMed

Li, Bing; Sheng, Minjie; Xie, Liqi; Liu, Feng; Yan, Guoquan; Wang, Weifang; Lin, Anjuan; Zhao, Fei; Chen, Yihui

2014-01-09

Diabetes mellitus has been shown to be associated with and complicated by dry eye syndrome. We sought to examine and compare the tear film proteome of type 2 diabetic patients with or without dry eye syndrome and normal subjects using two-dimensional nano-liquid chromatography coupled with tandem mass spectrometry (MS)-based proteomics. Tears were collected from eight type 2 diabetes patients with dry eye syndrome, eight type 2 diabetes patients without dry eye syndrome, and eight normal subjects. Tear breakup time (BUT) was determined, and tear proteins were prepared and analyzed using two-dimensional strong cation-exchange/reversed-phase nano-scale liquid chromatography MS. All MS/MS spectra were identified by using SEQUEST against the human International Protein Index (IPI) database and the relative abundance of individual proteins was assessed by spectral counting. Tear BUT was significantly lower in patients with diabetes and dry eye syndrome than in patients with diabetes only and normal subjects. Analysis of spectral counts of tear proteins showed that, compared to healthy controls, patients with diabetes and dry eye syndrome had increased expression of apoptosis-related proteins, like annexin A1, and immunity- and inflammation-related proteins, including neutrophil elastase 2 and clusterin, and glycometabolism-related proteins, like apolipoprotein A-II. Dry eye syndrome in diabetic patients is associated with aberrant expression of tear proteins, and the findings could lead to identification of novel pathways for therapeutic targeting and new diagnostic markers.

Morphological alterations within the peripheral fixation of the iris dilator muscle in eyes with pigmentary glaucoma.

PubMed

Flügel-Koch, Cassandra M; Tektas, Ozan Y; Kaufman, Paul L; Paulsen, Friedrich P; Lütjen-Drecoll, Elke

2014-06-17

To analyze the peripheral fixation of the iris dilator muscle in normal eyes and in eyes with pigmentary glaucoma (PG). Using 63 control eyes (age 18 months-99 years), the peripheral iris dilator was investigated by light microscopy, immunohistochemistry, and electron microscopy. Development was studied using 18 differently aged fetal eyes stained immunohistochemically against α-smooth muscle (SM) actin. The peripheral iris dilator muscle in PG was analyzed using semithin and ultrathin sections of six glutaraldehyde-fixed eyes from three donors aged 38, 62, and 74 years. In normal eyes, the peripheral end of the iris dilator muscle is arranged in a sphincter-like manner. Arcade-shaped tendinous connections associated with myofibroblasts (iridial strands) anchor the iris dilator within the elastic-fibromuscular ciliary meshwork that also serves as fixation area for the elastic tendons of the inner ciliary muscle portions. The iridial strands are innervated and can adapt their length during accommodation. The PG eyes show incomplete circular bundles and iridial strands that are mainly anchored to the iris stroma and the flexible uveal parts of the trabecular meshwork. The normal anchorage of the peripheral iris dilator and its presumably neuronally regulated length adaptation stabilize the peripheral iris during accommodation. Insufficient fixation in PG could promote posterior bowing of the iris with rubbing against the zonular fibers and pigment liberation from the iris pigmented epithelium. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

Eyes with Suspicious Appearance of the Optic Disc and Normal Intraocular Pressure: Using Clinical and Epidemiological Characteristics to Differentiate Those with and without Glaucoma.

PubMed

Dias, Diego T; Ushida, Michele; Sousa, Marina C; Dorairaj, Syril; Biteli, Luis G; Leite, Mauro T; Paranhos, Augusto; Prata, Tiago S

2016-01-01

Among all glaucoma suspects, eyes with optic nerve head features suspicious or suggestive of early glaucoma are probably those that offer the greatest challenge for clinicians. In contrast with the robust longitudinal data published on ocular hypertension, there is no specific management guideline for these patients. Therefore, evaluating eyes with suspicious optic disc appearance and normal intraocular pressure (IOP), we sought to investigate potential differences in clinical and epidemiological characteristics to differentiate those with normal-tension glaucoma (NTG) from those with presumed large physiological optic disc cups (pLPC). In this observational case-control study, we consecutively enrolled individuals with pLPC and NTG. All eyes had vertical cup-to-disc ratio (VCDR)≥0.6 and untreated IOP<21 mmHg. Glaucomatous eyes had reproducible visual field defects. Eyes with pLPC required normal visual fields and ≥30 months of follow-up with no evidence of glaucomatous neuropathy. Clinical and epidemiological parameters were compared between groups. Eighty-four individuals with pLPC and 40 NTG patients were included. Regarding our main results, NTG patients were significantly older and with a higher prevalence of Japanese descendants (p<0.01). Not only did pLPC eyes have smaller mean VCDR, but also larger optic discs (p≤0.04). There were no significant differences for gender, central corneal thickness, and spherical equivalent (p≥0.38). Significant odds ratios (OR) were found for race (OR = 2.42; for Japanese ancestry), age (OR = 1.05), VCDR (OR = 5.03), and disc size (OR = 0.04; p≤0.04). In conclusion, in patients with suspicious optic disc and normal IOP, those with older age, Japanese ancestry, smaller optic discs, and larger VCDR are more likely to have NTG, and therefore, deserve deeper investigation and closer monitoring.

Reproducibility of retinal nerve fiber layer thickness measures using eye tracking in children with nonglaucomatous optic neuropathy.

PubMed

Rajjoub, Raneem D; Trimboli-Heidler, Carmelina; Packer, Roger J; Avery, Robert A

2015-01-01

To determine the intra- and intervisit reproducibility of circumpapillary retinal nerve fiber layer (RNFL) thickness measures using eye tracking-assisted spectral-domain optical coherence tomography (SD OCT) in children with nonglaucomatous optic neuropathy. Prospective longitudinal study. Circumpapillary RNFL thickness measures were acquired with SD OCT using the eye-tracking feature at 2 separate study visits. Children with normal and abnormal vision (visual acuity ≥ 0.2 logMAR above normal and/or visual field loss) who demonstrated clinical and radiographic stability were enrolled. Intra- and intervisit reproducibility was calculated for the global average and 9 anatomic sectors by calculating the coefficient of variation and intraclass correlation coefficient. Forty-two subjects (median age 8.6 years, range 3.9-18.2 years) met inclusion criteria and contributed 62 study eyes. Both the abnormal and normal vision cohort demonstrated the lowest intravisit coefficient of variation for the global RNFL thickness. Intervisit reproducibility remained good for those with normal and abnormal vision, although small but statistically significant increases in the coefficient of variation were observed for multiple anatomic sectors in both cohorts. The magnitude of visual acuity loss was significantly associated with the global (ß = 0.026, P < .01) and temporal sector coefficient of variation (ß = 0.099, P < .01). SD OCT with eye tracking demonstrates highly reproducible RNFL thickness measures. Subjects with vision loss demonstrate greater intra- and intervisit variability than those with normal vision. Copyright © 2015 Elsevier Inc. All rights reserved.

Influence of Ophthalmic Solutions on Tear Components.

PubMed

Shigeyasu, Chika; Yamada, Masakazu; Akune, Yoko

2016-11-01

Tear fluids are a mixture of secretions derived from lacrimal glands, accessory lacrimal glands, conjunctiva, and meibomian glands. Compositional changes to tears occur in the normal state and during ocular surface disease, such as dry eye conditions. We have investigated compositional changes to tears after topical application of ophthalmic solutions, with regard to tear-specific proteins (secretory immunoglobulin A, lactoferrin, lipocalin-1, and lysozyme) and ocular surface mucin in normal and dry eye conditions using high-performance liquid chromatography. After application of saline solution (0.9% sodium chloride) in normal subjects, transient but significant decreases in all tear components were observed. The recovery of protein concentrations took up to 30 minutes and lasted longer when the saline solution was applied more frequently. When applying ophthalmic solutions, a balance between washout and dilutional effects should be considered in addition to the therapeutic effect. Investigation of the effect of diquafosol solution (3%) in normal subjects revealed a significant increase in sialic acid concentration, a marker of ocular mucin, at 5 minutes after application, whereas a significant decrease was observed with saline. This result indicates the accelerated secretion of mucin from ocular tissues induced by diquafosol. A clinical study to determine the efficacy of diquafosol in patients with dry eye revealed improvements in tear breakup time, keratoconjunctival staining scores, and Schirmer test score, accompanied by an increase in sialic acid concentration in tears. Investigating normal and dry eye conditions through tear analysis may clarify the pathophysiology of dry eye conditions and support the efficacy of treatments.

Hard to “tune in”: neural mechanisms of live face-to-face interaction with high-functioning autistic spectrum disorder

PubMed Central

Tanabe, Hiroki C.; Kosaka, Hirotaka; Saito, Daisuke N.; Koike, Takahiko; Hayashi, Masamichi J.; Izuma, Keise; Komeda, Hidetsugu; Ishitobi, Makoto; Omori, Masao; Munesue, Toshio; Okazawa, Hidehiko; Wada, Yuji; Sadato, Norihiro

2012-01-01

Persons with autism spectrum disorders (ASD) are known to have difficulty in eye contact (EC). This may make it difficult for their partners during face to face communication with them. To elucidate the neural substrates of live inter-subject interaction of ASD patients and normal subjects, we conducted hyper-scanning functional MRI with 21 subjects with autistic spectrum disorder (ASD) paired with typically-developed (normal) subjects, and with 19 pairs of normal subjects as a control. Baseline EC was maintained while subjects performed real-time joint-attention task. The task-related effects were modeled out, and inter-individual correlation analysis was performed on the residual time-course data. ASD–Normal pairs were less accurate at detecting gaze direction than Normal–Normal pairs. Performance was impaired both in ASD subjects and in their normal partners. The left occipital pole (OP) activation by gaze processing was reduced in ASD subjects, suggesting that deterioration of eye-cue detection in ASD is related to impairment of early visual processing of gaze. On the other hand, their normal partners showed greater activity in the bilateral occipital cortex and the right prefrontal area, indicating a compensatory workload. Inter-brain coherence in the right IFG that was observed in the Normal-Normal pairs (Saito et al., 2010) during EC diminished in ASD–Normal pairs. Intra-brain functional connectivity between the right IFG and right superior temporal sulcus (STS) in normal subjects paired with ASD subjects was reduced compared with in Normal–Normal pairs. This functional connectivity was positively correlated with performance of the normal partners on the eye-cue detection. Considering the integrative role of the right STS in gaze processing, inter-subject synchronization during EC may be a prerequisite for eye cue detection by the normal partner. PMID:23060772

Nonlinear matching measure for the analysis of on-off type DNA microarray images

NASA Astrophysics Data System (ADS)

Kim, Jong D.; Park, Misun; Kim, Jongwon

2003-07-01

In this paper, we propose a new nonlinear matching measure for automatic analysis of the on-off type DNA microarray images in which the hybridized spots are detected by the template matching method. The targeting spots of HPV DNA chips are designed for genotyping the human papilloma virus(HPV). The proposed measure is obtained by binarythresholding over the whole template region and taking the number of white pixels inside the spotted area. This measure is evaluated in terms of the accuracy of the estimated marker location to show better performance than the normalized covariance.

Symptomatic and asymptomatic benign prostatic hyperplasia: Molecular differentiation by using microarrays

NASA Astrophysics Data System (ADS)

Prakash, Kulkarni; Pirozzi, Gregorio; Elashoff, Michael; Munger, William; Waga, Iwao; Dhir, Rajiv; Kakehi, Yoshiyuki; Getzenberg, Robert H.

2002-05-01

Benign prostatic hyperplasia (BPH) is a disease of unknown etiology that significantly affects the quality of life in aging men. Histologic BPH may present itself either as symptomatic or asymptomatic in nature. To elucidate the molecular differences underlying BPH, gene expression profiles from the prostate transition zone tissue have been analyzed by using microarrays. A set of 511 differentially expressed genes distinguished symptomatic and asymptomatic BPH. This genetic signature separates BPH from normal tissue but does not seem to change with age. These data could provide novel approaches for alleviating symptoms and hyperplasia in BPH.

Novel statistical framework to identify differentially expressed genes allowing transcriptomic background differences.

PubMed

Ling, Zhi-Qiang; Wang, Yi; Mukaisho, Kenichi; Hattori, Takanori; Tatsuta, Takeshi; Ge, Ming-Hua; Jin, Li; Mao, Wei-Min; Sugihara, Hiroyuki

2010-06-01

Tests of differentially expressed genes (DEGs) from microarray experiments are based on the null hypothesis that genes that are irrelevant to the phenotype/stimulus are expressed equally in the target and control samples. However, this strict hypothesis is not always true, as there can be several transcriptomic background differences between target and control samples, including different cell/tissue types, different cell cycle stages and different biological donors. These differences lead to increased false positives, which have little biological/medical significance. In this article, we propose a statistical framework to identify DEGs between target and control samples from expression microarray data allowing transcriptomic background differences between these samples by introducing a modified null hypothesis that the gene expression background difference is normally distributed. We use an iterative procedure to perform robust estimation of the null hypothesis and identify DEGs as outliers. We evaluated our method using our own triplicate microarray experiment, followed by validations with reverse transcription-polymerase chain reaction (RT-PCR) and on the MicroArray Quality Control dataset. The evaluations suggest that our technique (i) results in less false positive and false negative results, as measured by the degree of agreement with RT-PCR of the same samples, (ii) can be applied to different microarray platforms and results in better reproducibility as measured by the degree of DEG identification concordance both intra- and inter-platforms and (iii) can be applied efficiently with only a few microarray replicates. Based on these evaluations, we propose that this method not only identifies more reliable and biologically/medically significant DEG, but also reduces the power-cost tradeoff problem in the microarray field. Source code and binaries freely available for download at http://comonca.org.cn/fdca/resources/softwares/deg.zip.

Characteristics and Ophthalmic Manifestations of the Classic Dengue Fever Epidemic in Singapore (2005-2006).

PubMed

Koh, Yan Tong; Sanjay, Srinivasan

2013-01-01

The aim of this study was to report the characteristics and ophthalmic manifestations associated with dengue fever (DF) in the 2005-2006 DF epidemic in Singapore. A retrospective case series. Eleven patients (7 males, 4 females) who were 14 to 40 years old (mean age, 27.3 years) with visual complaints occurring 1 to 2 weeks after the onset of DF underwent a complete ophthalmologic examination. The presenting visual acuity (VA) ranged from 6/6 to counting fingers. Five patients had bilateral eye involvement. Ophthalmic findings included retinal hemorrhages (15 eyes), cotton wool spots (15 eyes), retinal pigment epithelium alterations (5 eyes), optic disc swelling (3 eyes), foveolitis (3 eyes), and hyperemia (2 eyes). Impaired color vision was noted in 12 eyes. Visual field defects were noted in 13 eyes; 4 of these eyes were asymptomatic. Fundus fluorescein angiography was done in 9 patients; the findings include choroidal hyperfluorescence (9 eyes), blocked fluorescence (8 eyes), and capillary nonperfusion (1 eye). In 2 eyes, it was normal. Electrophysiology confirmed optic neuropathy in 3 eyes and maculopathy in 1 eye. The follow-up ranged from 12 days to 12 months. The VA at the last follow-up ranged from no light perception to 6/6. Visual field abnormalities were noted in 5 eyes despite a normal VA. Dengue fever is associated with a wide spectrum of ophthalmic manifestations. Rarely, ophthalmic complications in DF can result in permanent visual impairment. Further work can be done to elucidate the relationship between systemic and ocular manifestations of DF.

Unilateral Amblyopia Affects Two Eyes: Fellow Eye Deficits in Amblyopia.

PubMed

Meier, Kimberly; Giaschi, Deborah

2017-03-01

Unilateral amblyopia is a visual disorder that arises after selective disruption of visual input to one eye during critical periods of development. In the clinic, amblyopia is understood as poor visual acuity in an eye that was deprived of pattern vision early in life. By its nature, however, amblyopia has an adverse effect on the development of a binocular visual system and the interactions between signals from two eyes. Visual functions aside from visual acuity are impacted, and many studies have indicated compromised sensitivity in the fellow eye even though it demonstrates normal visual acuity. While these fellow eye deficits have been noted, no overarching theory has been proposed to describe why and under what conditions the fellow eye is impacted by amblyopia. Here, we consider four explanations that may account for decreased fellow eye sensitivity: the fellow eye is adversely impacted by treatment for amblyopia; the maturation of the fellow eye is delayed by amblyopia; fellow eye sensitivity is impacted for visual functions that rely on binocular cortex; and fellow eye deficits reflect an adaptive mechanism that works to equalize the sensitivity of the two eyes. To evaluate these ideas, we describe five visual functions that are commonly reported to be deficient in the amblyopic eye (hyperacuity, contrast sensitivity, spatial integration, global motion, and motion-defined form), and unify the current evidence for fellow eye deficits. Further research targeted at exploring fellow eye deficits in amblyopia will provide us with a broader understanding of normal visual development and how amblyopia impacts the developing visual system.

Anterior Segment Morphology in Primary Angle Closure Glaucoma using Ultrasound Biomicroscopy

PubMed Central

Balakrishna, Nagalla

2017-01-01

Aim To evaluate the configuration of the anterior chamber angle quantitatively and study the morphological changes in the eye with ultrasound biomicroscopy (UBM) in primary angle closure glaucoma (PACG) patients after laser peripheral iridotomy (LPI). Materials and methods A total of 185 eyes of 185 PACG patients post-LPI and 126 eyes of 126 normal subjects were included in this prospective study. All subjects underwent complete ophthalmic evaluation, A-scan biometry, and UBM. The anterior segment and angle parameters were measured quantitatively and compared in both groups using Student’s t-test. Results The PACG patients had shorter axial length, shallower central anterior chamber depth anterior chamber depth (ACD), and anteriorly located lens when compared with normal subjects. Trabecular iris angle (TIA) was significantly narrow (5.73 ± 7.76°) in patients with PACG when compared with normal subjects (23.75 ± 9.38°). The angle opening distance at 500 pm from scleral spur (AOD 500), trabecular-ciliary process distance (TCPD), iris-ciliary process distance (ICPD), and iris-zonule distance (IZD) were significantly shorter in patients with PACG than in normal subjects (p < 0.0001). The iris lens angle (ILA), scleral-iris angle (SIA), and scleral-ciliary process angle (SCPA) were significantly narrower in patients with PACG than in normal subjects (p < 0.0001). The iris-lens contact distance (ILCD) was greater in PACG group than in normal (p = 0.001). Plateau iris was seen in 57/185 (30.8%) of the eyes. Anterior positioned ciliary processes were seen in 130/185 eyes (70.3%) of eyes. Conclusion In PACG patients, persistent apposition angle closure is common even after LPI, which could be due to anterior rotation of ciliary body and plateau iris and overcrowding of anterior segment due to shorter axial length and relative anterior lens position. How to cite this article: Mansoori T, Balakrishna N. Anterior Segment Morphology in Primary Angle Closure Glaucoma using Ultrasound Biomicroscopy. J Curr Glaucoma Pract 2017;11(3):86-91. PMID:29151682

Gene expression profile of mouse prostate tumors reveals dysregulations in major biological processes and identifies potential murine targets for preclinical development of human prostate cancer therapy.

PubMed

Haram, Kerstyn M; Peltier, Heidi J; Lu, Bin; Bhasin, Manoj; Otu, Hasan H; Choy, Bob; Regan, Meredith; Libermann, Towia A; Latham, Gary J; Sanda, Martin G; Arredouani, Mohamed S

2008-10-01

Translation of preclinical studies into effective human cancer therapy is hampered by the lack of defined molecular expression patterns in mouse models that correspond to the human counterpart. We sought to generate an open source TRAMP mouse microarray dataset and to use this array to identify differentially expressed genes from human prostate cancer (PCa) that have concordant expression in TRAMP tumors, and thereby represent lead targets for preclinical therapy development. We performed microarrays on total RNA extracted and amplified from eight TRAMP tumors and nine normal prostates. A subset of differentially expressed genes was validated by QRT-PCR. Differentially expressed TRAMP genes were analyzed for concordant expression in publicly available human prostate array datasets and a subset of resulting genes was analyzed by QRT-PCR. Cross-referencing differentially expressed TRAMP genes to public human prostate array datasets revealed 66 genes with concordant expression in mouse and human PCa; 56 between metastases and normal and 10 between primary tumor and normal tissues. Of these 10 genes, two, Sox4 and Tubb2a, were validated by QRT-PCR. Our analysis also revealed various dysregulations in major biologic pathways in the TRAMP prostates. We report a TRAMP microarray dataset of which a gene subset was validated by QRT-PCR with expression patterns consistent with previous gene-specific TRAMP studies. Concordance analysis between TRAMP and human PCa associated genes supports the utility of the model and suggests several novel molecular targets for preclinical therapy.

Glaucomatous patterns in Frequency Doubling Technology (FDT) perimetry data identified by unsupervised machine learning classifiers.

PubMed

Bowd, Christopher; Weinreb, Robert N; Balasubramanian, Madhusudhanan; Lee, Intae; Jang, Giljin; Yousefi, Siamak; Zangwill, Linda M; Medeiros, Felipe A; Girkin, Christopher A; Liebmann, Jeffrey M; Goldbaum, Michael H

2014-01-01

The variational Bayesian independent component analysis-mixture model (VIM), an unsupervised machine-learning classifier, was used to automatically separate Matrix Frequency Doubling Technology (FDT) perimetry data into clusters of healthy and glaucomatous eyes, and to identify axes representing statistically independent patterns of defect in the glaucoma clusters. FDT measurements were obtained from 1,190 eyes with normal FDT results and 786 eyes with abnormal FDT results from the UCSD-based Diagnostic Innovations in Glaucoma Study (DIGS) and African Descent and Glaucoma Evaluation Study (ADAGES). For all eyes, VIM input was 52 threshold test points from the 24-2 test pattern, plus age. FDT mean deviation was -1.00 dB (S.D. = 2.80 dB) and -5.57 dB (S.D. = 5.09 dB) in FDT-normal eyes and FDT-abnormal eyes, respectively (p<0.001). VIM identified meaningful clusters of FDT data and positioned a set of statistically independent axes through the mean of each cluster. The optimal VIM model separated the FDT fields into 3 clusters. Cluster N contained primarily normal fields (1109/1190, specificity 93.1%) and clusters G1 and G2 combined, contained primarily abnormal fields (651/786, sensitivity 82.8%). For clusters G1 and G2 the optimal number of axes were 2 and 5, respectively. Patterns automatically generated along axes within the glaucoma clusters were similar to those known to be indicative of glaucoma. Fields located farther from the normal mean on each glaucoma axis showed increasing field defect severity. VIM successfully separated FDT fields from healthy and glaucoma eyes without a priori information about class membership, and identified familiar glaucomatous patterns of loss.

The Initiation of Smooth Pursuit is Delayed in Anisometropic Amblyopia

PubMed Central

Raashid, Rana Arham; Liu, Ivy Ziqian; Blakeman, Alan; Goltz, Herbert C.; Wong, Agnes M. F.

2016-01-01

Purpose Several behavioral studies have shown that the reaction times of visually guided movements are slower in people with amblyopia, particularly during amblyopic eye viewing. Here, we tested the hypothesis that the initiation of smooth pursuit eye movements, which are responsible for accurately keeping moving objects on the fovea, is delayed in people with anisometropic amblyopia. Methods Eleven participants with anisometropic amblyopia and 14 visually normal observers were asked to track a step-ramp target moving at ±15°/s horizontally as quickly and as accurately as possible. The experiment was conducted under three viewing conditions: amblyopic/nondominant eye, binocular, and fellow/dominant eye viewing. Outcome measures were smooth pursuit latency, open-loop gain, steady state gain, and catch-up saccade frequency. Results Participants with anisometropic amblyopia initiated smooth pursuit significantly slower during amblyopic eye viewing (206 ± 20 ms) than visually normal observers viewing with their nondominant eye (183 ± 17 ms, P = 0.002). However, mean pursuit latency in the anisometropic amblyopia group during binocular and monocular fellow eye viewing was comparable to the visually normal group. Mean open-loop gain, steady state gain, and catch-up saccade frequency were similar between the two groups, but participants with anisometropic amblyopia exhibited more variable steady state gain (P = 0.045). Conclusions This study provides evidence of temporally delayed smooth pursuit initiation in anisometropic amblyopia. After initiation, the smooth pursuit velocity profile in anisometropic amblyopia participants is similar to visually normal controls. This finding differs from what has been observed previously in participants with strabismic amblyopia who exhibit reduced smooth pursuit velocity gains with more catch-up saccades. PMID:27070109

A new model of strabismic amblyopia: Loss of spatial acuity due to increased temporal dispersion of geniculate X-cell afferents on to cortical neurons.

PubMed

Crewther, D P; Crewther, S G

2015-09-01

Although the neural locus of strabismic amblyopia has been shown to lie at the first site of binocular integration, first in cat and then in primate, an adequate mechanism is still lacking. Here we hypothesise that increased temporal dispersion of LGN X-cell afferents driven by the deviating eye onto single cortical neurons may provide a neural mechanism for strabismic amblyopia. This idea was investigated via single cell extracellular recordings of 93 X and 50 Y type LGN neurons from strabismic and normal cats. Both X and Y neurons driven by the non-deviating eye showed shorter latencies than those driven by either the strabismic or normal eyes. Also the mean latency difference between X and Y neurons was much greater for the strabismic cells compared with the other two groups. The incidence of lagged X-cells driven by the deviating eye of the strabismic cats was higher than that of LGN X-cells from normal animals. Remarkably, none of the cells recorded from the laminae driven by the non-deviating eye were of the lagged class. A simple computational model was constructed in which a mixture of lagged and non-lagged afferents converge on to single cortical neurons. Model cut-off spatial frequencies to a moving grating stimulus were sensitive to the temporal dispersion of the geniculate afferents. Thus strabismic amblyopia could be viewed as a lack of developmental tuning of geniculate lags for neurons driven by the amblyopic eye. Monocular control of fixation by the non-deviating eye is associated with reduced incidence of lagged neurons, suggesting that in normal vision, lagged neurons might play a role in maintaining binocular connections for cortical neurons. Copyright © 2014 Elsevier Ltd. All rights reserved.

MIPHENO: Data normalization for high throughput metabolic analysis.

EPA Science Inventory

High throughput methodologies such as microarrays, mass spectrometry and plate-based small molecule screens are increasingly used to facilitate discoveries from gene function to drug candidate identification. These large-scale experiments are typically carried out over the course...

[Technology of analysis of epigenetic and structural changes of epithelial tumors genome with NotI-microarrays by the example of human chromosome].

PubMed

Pavlova, T V; Kashuba, V I; Muravenko, O V; Yenamandra, S P; Ivanova, T A; Zabarovskaia, V I; Rakhmanaliev, E R; Petrenko, L A; Pronina, I V; Loginov, V I; Iurkevich, O Iu; Kiselev, L L; Zelenin, A V; Zabarovskiĭ, E R

2009-01-01

New comparative genome hybridization technology on NotI-microarrays is presented (Karolinska Institute International Patent WO02/086163). The method is based on comparative genome hybridization of NotI-probes from tumor and normal genomic DNA with the principle of new DNA NotI-microarrays. Using this method 181 NotI linking loci from human chromosome 3 were analyzed in 200 malignant tumor samples from different organs: kidney, lung, breast, ovary, cervical, prostate. Most frequently (more than in 30%) aberrations--deletions, methylation,--were identified in NotI-sites located in MINT24, BHLHB2, RPL15, RARbeta1, ITGA9, RBSP3, VHL, ZIC4 genes, that suggests they probably are involved in cancer development. Methylation of these genomic loci was confirmed by methylation-specific PCR and bisulfite sequencing. The results demonstrate perspective of using this method to solve some oncogenomic problems.

Comparison of RNFL thickness and RPE-normalized RNFL attenuation coefficient for glaucoma diagnosis

NASA Astrophysics Data System (ADS)

Vermeer, K. A.; van der Schoot, J.; Lemij, H. G.; de Boer, J. F.

2013-03-01

Recently, a method to determine the retinal nerve fiber layer (RNFL) attenuation coefficient, based on normalization on the retinal pigment epithelium, was introduced. In contrast to conventional RNFL thickness measures, this novel measure represents a scattering property of the RNFL tissue. In this paper, we compare the RNFL thickness and the RNFL attenuation coefficient on 10 normal and 8 glaucomatous eyes by analyzing the correlation coefficient and the receiver operator curves (ROCs). The thickness and attenuation coefficient showed moderate correlation (r=0.82). Smaller correlation coefficients were found within normal (r=0.55) and glaucomatous (r=0.48) eyes. The full separation between normal and glaucomatous eyes based on the RNFL attenuation coefficient yielded an area under the ROC (AROC) of 1.0. The AROC for the RNFL thickness was 0.9875. No statistically significant difference between the two measures was found by comparing the AROC. RNFL attenuation coefficients may thus replace current RNFL thickness measurements or be combined with it to improve glaucoma diagnosis.

Pilot Study: The Role of the Hemispheric Lateralization in Mental Disorders by Use of the Limb (Eye, Hand, Foot) Dominance.

PubMed

Goodarzi, Naser; Dabbaghi, Parviz; Valipour, Habib; Vafadari, Behnam

2015-04-01

Based on the previous studies, we know that the hemispheric lateralization defects, increase the probability of psychological disorders. We also know that dominant limb is controlled by dominant hemisphere and limb preference is used as an indicator for hemisphere dominance. In this study we attempted to explore the hemispheric dominance by the use of three limbs (hand, foot and eye). We performed this survey on two samples, psychiatric patients compared with normal population. For this purpose, knowing that the organ dominance is stabilized in adolescence, and age has no effect on the people above 15, we used 48 high school girls and 65 boys as the final samples of normal population. The patient group included 57 male and 26 female who were chronic psychiatric patients. The result shows that left-eye dominance is more in patients than the normal group (P=0.000) but the handedness and footedness differences are not significance. In psychotic, bipolar and depressive disorders, eye dominance had significant difference (P=0.018). But this is not true about hand and foot dominance. Our findings proved that generally in psychiatric patients, left-eye dominance is more common, left-eye dominance is also more in psychotic and depressive disorders. It is less common in bipolar disorders.

Experimental murine myopia induces collagen type Iα1 (COL1A1) DNA methylation and altered COL1A1 messenger RNA expression in sclera

PubMed Central

Zhou, Xiangtian; Ji, Fengtao; An, Jianhong; Zhao, Fuxin; Shi, Fanjun; Huang, Furong; Li, Yuan; Jiao, Shiming; Yan, Dongsheng; Chen, Xiaoyan; Chen, JiangFan

2012-01-01

Purpose To investigate whether myopia development is associated with changes of scleral DNA methylation in cytosine-phosphate-guanine (CpG) sites in the collagen 1A1 (COL1A1) promoter and messenger RNA (mRNA) levels following murine form deprivation myopia. Methods Fifty-seven C57BL/6 mice (postnatal day 23) were randomly assigned to four groups: (1) monocular form deprivation (MD) in which a diffuser lens was placed over one eye for 28 days; (2) normal controls without MD; (3) MD recovery in which the diffuser lens was removed for seven days; and (4) MD recovery normal controls. The DNA methylation pattern in COL1A1 promoter and exon 1 was determined by bisulfite DNA sequencing, and the COL1A1 mRNA level in sclera was determined by quantitative PCR. Results MD was found to induce myopia in the treated eyes. Six CpG sites in the promoter and exon 1 region of COL1A1 were methylated with significantly higher frequency in the treated eyes than normal control eyes (p<0.05), with CpG island methylation in MD-contralateral eyes being intermediate. Consistent with the CpG methylation, scleral COL1A1 mRNA was reduced by 57% in the MD-treated eyes compared to normal controls (p<0.05). After seven days of MD recovery, CpG methylation was significantly reduced (p=0.01). The methylation patterns returned to near normal level in five CpG sites, but the sixth was hypomethylated compared to normal controls. Conclusions In parallel with the development of myopia and the reduced COL1A1 mRNA, the frequency of methylation in CpG sites of the COL1A1 promoter/exon 1 increased during MD and returned to near normal during recovery. Thus, hypermethylation of CpG sites in the promoter/exon 1 of COL1A1 may underlie reduced collagen synthesis at the transcriptional level in myopic scleras. PMID:22690110

Reliability of Pentacam HR Thickness Maps of the Entire Cornea in Normal, Post-Laser In Situ Keratomileusis, and Keratoconus Eyes.

PubMed

Xu, Zhe; Peng, Mei; Jiang, Jun; Yang, Chun; Zhu, Weigen; Lu, Fan; Shen, Meixiao

2016-02-01

To measure the repeatability and reproducibility of Pentacam HR system thickness maps for the entire cornea in normal, post-laser in situ keratomileusis (post-LASIK), and keratoconus (KC) eyes. Reliability study. Sixty normal subjects (60 eyes), 30 post-LASIK subjects (60 eyes), and 14 KC patients (27 eyes) were imaged with the Pentacam HR system by 2 well-trained operators. For pachymetry the cornea was divided into 4 zones: a central zone (2-mm diameter) and concentric pericentral zone (2-5 mm), transitional zone (5-7 mm), and peripheral zone (7-10 mm). The 3 concentric zones were subdivided into 8 sectors. Intraobserver repeatability and interobserver reproducibility of entire corneal thickness maps were tested by the repeatability and reproducibility coefficients, intraclass correlation coefficients, coefficient of variation, and 95% limits of agreement. From central to peripheral zones, the precision of corneal thickness measurements became gradually smaller. Central zone repeatability and reproducibility were the best in the normal, post-LASIK, and KC groups. The peripheral superior sectors showed poorer repeatability and reproducibility for all subjects. The intraobserver repeatability and interobserver reproducibility for all zones were ≤19.3 μm, ≤22.1 μm, and ≤20.7 μm, in the normal, post-LASIK, and KC groups, respectively. The intraobserver and interobserver coefficients of variation for all zones were ≤1.3%, ≤1.6%, and ≤1.6% for all 3 groups. Pentacam HR system pachymetry of the entire cornea provided good precision in normal, post-LASIK, and KC corneas. Thickness measurements in the peripheral cornea should be interpreted with caution in abnormal corneas after surgery or with diseases. Copyright © 2016 Elsevier Inc. All rights reserved.

Regulation of gene expression in the mammalian eye and its relevance to eye disease.

PubMed

Scheetz, Todd E; Kim, Kwang-Youn A; Swiderski, Ruth E; Philp, Alisdair R; Braun, Terry A; Knudtson, Kevin L; Dorrance, Anne M; DiBona, Gerald F; Huang, Jian; Casavant, Thomas L; Sheffield, Val C; Stone, Edwin M

2006-09-26

We used expression quantitative trait locus mapping in the laboratory rat (Rattus norvegicus) to gain a broad perspective of gene regulation in the mammalian eye and to identify genetic variation relevant to human eye disease. Of >31,000 gene probes represented on an Affymetrix expression microarray, 18,976 exhibited sufficient signal for reliable analysis and at least 2-fold variation in expression among 120 F(2) rats generated from an SR/JrHsd x SHRSP intercross. Genome-wide linkage analysis with 399 genetic markers revealed significant linkage with at least one marker for 1,300 probes (alpha = 0.001; estimated empirical false discovery rate = 2%). Both contiguous and noncontiguous loci were found to be important in regulating mammalian eye gene expression. We investigated one locus of each type in greater detail and identified putative transcription-altering variations in both cases. We found an inserted cREL binding sequence in the 5' flanking sequence of the Abca4 gene associated with an increased expression level of that gene, and we found a mutation of the gene encoding thyroid hormone receptor beta2 associated with a decreased expression level of the gene encoding short-wavelength sensitive opsin (Opn1sw). In addition to these positional studies, we performed a pairwise analysis of gene expression to identify genes that are regulated in a coordinated manner and used this approach to validate two previously undescribed genes involved in the human disease Bardet-Biedl syndrome. These data and analytical approaches can be used to facilitate the discovery of additional genes and regulatory elements involved in human eye disease.

Analysis of the Transcriptomes Downstream of Eyeless and the Hedgehog, Decapentaplegic and Notch Signaling Pathways in Drosophila melanogaster

PubMed Central

Nfonsam, Landry E.; Cano, Carlos; Mudge, Joann; Schilkey, Faye D.; Curtiss, Jennifer

2012-01-01

Tissue-specific transcription factors are thought to cooperate with signaling pathways to promote patterned tissue specification, in part by co-regulating transcription. The Drosophila melanogaster Pax6 homolog Eyeless forms a complex, incompletely understood regulatory network with the Hedgehog, Decapentaplegic and Notch signaling pathways to control eye-specific gene expression. We report a combinatorial approach, including mRNAseq and microarray analyses, to identify targets co-regulated by Eyeless and Hedgehog, Decapentaplegic or Notch. Multiple analyses suggest that the transcriptomes resulting from co-misexpression of Eyeless+signaling factors provide a more complete picture of eye development compared to previous efforts involving Eyeless alone: (1) Principal components analysis and two-way hierarchical clustering revealed that the Eyeless+signaling factor transcriptomes are closer to the eye control transcriptome than when Eyeless is misexpressed alone; (2) more genes are upregulated at least three-fold in response to Eyeless+signaling factors compared to Eyeless alone; (3) based on gene ontology analysis, the genes upregulated in response to Eyeless+signaling factors had a greater diversity of functions compared to Eyeless alone. Through a secondary screen that utilized RNA interference, we show that the predicted gene CG4721 has a role in eye development. CG4721 encodes a neprilysin family metalloprotease that is highly up-regulated in response to Eyeless+Notch, confirming the validity of our approach. Given the similarity between D. melanogaster and vertebrate eye development, the large number of novel genes identified as potential targets of Ey+signaling factors will provide novel insights to our understanding of eye development in D. melanogaster and humans. PMID:22952997

SU-F-T-51: Investigating the Effect of Eye Size and Eccentricity On Normal Tissue Doses From Eye Plaque Brachytherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Polsdofer, E; Crilly, R

Purpose: This study investigates the effect of eye size and eccentricity on doses to critical tissues by simulating doses in the Plaque Simulator (v. 6.3.1) software. Present OHSU plaque brachytherapy treatment focuses on delivering radiation to the tumor measured with ocular ultrasound plus a small margin and assumes the orbit has the dimensions of a “standard eye.” Accurately modeling the dimensions of the orbit requires a high resolution ocular CT. This study quantifies how standard differences in equatorial diameters and eccentricity affect calculated doses to critical structures in order to query the justification of the additional CT scan to themore » treatment planning process. Methods: Tumors of 10 mm × 10 mm × 5 mm were modeled at the 12:00:00 hour with a latitude of 45 degrees. Right eyes were modeled at a number of equatorial diameters from 17.5 to 28 mm for each of the standard non-notched COMS plaques with silastic inserts. The COMS plaques were fully loaded with uniform activity, centered on the tumor, and prescribed to a common tumor dose (85 Gy/100 hours). Variations in the calculated doses to normal structures were examined to see if the changes were significant. Results: The calculated dose to normal structures show a marked dependence on eye geometry. This is exemplified by fovea dose which more than doubled in the smaller eyes and nearly halved in the larger model. Additional significant dependence was found in plaque size on the calculated dose in spite of all plaques giving the same dose to the prescription point. Conclusion: The variation in dose with eye dimension fully justifies the addition of a high resolution ocular CT to the planning technique. Additional attention must be made to plaque size beyond simply covering the tumor when considering normal tissue dose.« less

Introduction of Two Novel Stiffness Parameters and Interpretation of Air Puff-Induced Biomechanical Deformation Parameters With a Dynamic Scheimpflug Analyzer.

PubMed

Roberts, Cynthia J; Mahmoud, Ashraf M; Bons, Jeffrey P; Hossain, Arif; Elsheikh, Ahmed; Vinciguerra, Riccardo; Vinciguerra, Paolo; Ambrósio, Renato

2017-04-01

To investigate two new stiffness parameters and their relationships with the dynamic corneal response (DCR) parameters and compare normal and keratoconic eyes. Stiffness parameters are defined as Resultant Pressure at inward applanation (A1) divided by corneal displacement. Stiffness parameter A1 uses displacement between the undeformed cornea and A1 and stiffness parameter highest concavity (HC) uses displacement from A1 to maximum deflection during HC. The spatial and temporal profiles of the Corvis ST (Oculus Optikgeräte, Wetzlar, Germany) air puff were characterized using hot wire anemometry. An adjusted air pressure impinging on the cornea at A1 (adjAP1) and an algorithm to biomechanically correct intraocular pressure based on finite element modelling (bIOP) were used for Resultant Pressure calculation (adjAP1 - bIOP). Linear regression analyses between DCR parameters and stiffness parameters were performed on a retrospective dataset of 180 keratoconic eyes and 482 normal eyes. DCR parameters from a subset of 158 eyes of 158 patients in each group were matched for bIOP and compared using t tests. A P value of less than .05 was considered statistically significant. All DCR parameters evaluated showed significant differences between normal and keratoconic eyes, except peak distance. Keratoconic eyes had lower stiffness parameter values, thinner pachymetry, shorter applanation lengths, greater absolute values of applanation velocities, earlier A1 times and later second applanation times, greater HC deformation amplitudes and HC deflection amplitudes, and lower HC radius of concave curvature (greater concave curvature). Most DCR parameters showed a significant relationship with both stiffness parameters in both groups. Keratoconic eyes demonstrated less resistance to deformation than normal eyes with similar IOP. The stiffness parameters may be useful in future biomechanical studies as potential biomarkers. [J Refract Surg. 2017;33(4):266-273.]. Copyright 2017, SLACK Incorporated.

Comparison of corneal power, astigmatism, and wavefront aberration measurements obtained by a point-source color light-emitting diode-based topographer, a Placido-disk topographer, and a combined Placido and dual Scheimpflug device.

PubMed

Ventura, Bruna V; Wang, Li; Ali, Shazia F; Koch, Douglas D; Weikert, Mitchell P

2015-08-01

To evaluate and compare the performance of a point-source color light-emitting diode (LED)-based topographer (color-LED) in measuring anterior corneal power and aberrations with that of a Placido-disk topographer and a combined Placido and dual Scheimpflug device. Cullen Eye Institute, Baylor College of Medicine, Houston, Texas USA. Retrospective observational case series. Normal eyes and post-refractive-surgery eyes were consecutively measured using color-LED, Placido, and dual-Scheimpflug devices. The main outcome measures were anterior corneal power, astigmatism, and higher-order aberrations (HOAs) (6.0 mm pupil), which were compared using the t test. There were no statistically significant differences in corneal power measurements in normal and post-refractive surgery eyes and in astigmatism magnitude in post-refractive surgery eyes between the color-LED device and Placido or dual Scheimpflug devices (all P > .05). In normal eyes, there were no statistically significant differences in 3rd-order coma and 4th-order spherical aberration between the color-LED and Placido devices and in HOA root mean square, 3rd-order coma, 3rd-order trefoil, 4th-order spherical aberration, and 4th-order secondary astigmatism between the color-LED and dual Scheimpflug devices (all P > .05). In post-refractive surgery eyes, the color-LED device agreed with the Placido and dual-Scheimpflug devices regarding 3rd-order coma and 4th-order spherical aberration (all P > .05). In normal and post-refractive surgery eyes, all 3 devices were comparable with respect to corneal power. The agreement in corneal aberrations varied. Drs. Wang, Koch, and Weikert are consultants to Ziemer Ophthalmic Systems AG. Dr. Koch is a consultant to Abbott Medical Optics, Inc., Alcon Surgical, Inc., and i-Optics Corp. Copyright © 2015 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

Mean Posterior Corneal Power and Astigmatism in Normal Versus Keratoconic Eyes.

PubMed

Feizi, Sepehr; Delfazayebaher, Siamak; Javadi, Mohammad Ali; Karimian, Farid; Ownagh, Vahid; Sadeghpour, Fatemeh

2018-01-01

To compare mean posterior corneal power and astigmatism in normal versus keratoconus affected eyes and determine the optimal cut-off points to maximize sensitivity and specificity in discriminating keratoconus from normal corneas. A total of 204 normal eyes and 142 keratoconus affected eyes were enrolled in this prospective comparative study. Mean posterior corneal power and astigmatism were measured using a dual Scheimpflug camera. Correlation coefficients were calculated to assess the relationship between the magnitudes of keratometric and posterior corneal astigmatism in the study groups. Receiver operating characteristic curves were used to compare the sensitivity and specificity of the measured parameters and to identify the optimal cut-off points for discriminating keratoconus from normal corneas. The mean posterior corneal power was -6.29 ± 0.20 D in the normal group and -7.77 ± 0.87 D in the keratoconus group ( P < 0.001). The mean magnitudes of the posterior corneal astigmatisms were -0.32 ± 0.15 D and -0.94 ± 0.39 D in the normal and keratoconus groups, respectively ( P < 0.001). Significant correlations were found between the magnitudes of keratometric and posterior corneal astigmatism in the normal (r=-0.76, P < 0.001) and keratoconus (r=-0.72, P < 0.001) groups. The mean posterior corneal power and astigmatism were highly reliable characteristics that distinguished keratoconus from normal corneas (area under the curve, 0.99 and 0.95, respectively). The optimal cut-off points of mean posterior corneal power and astigmatism were -6.70 D and -0.54 D, respectively. Mean posterior corneal power and astigmatism measured using a Galilei analyzer camera might have potential in diagnosing keratoconus. The cut-off points provided can be used for keratoconus screening.

Biochemical Measurements of Free Opsin in Macular Degeneration Eyes: Examining the 11-CIS Retinal Deficiency Hypothesis of Delayed Dark Adaptation (An American Ophthalmological Society Thesis).

PubMed

Hanneken, Anne; Neikirk, Thomas; Johnson, Jennifer; Kono, Masahiro

2017-08-01

To test the hypothesis that delayed dark adaptation in patients with macular degeneration is due to an excess of free unliganded opsin (apo-opsin) and a deficiency of the visual chromophore, 11 -cis retinal, in rod outer segments. A total of 50 human autopsy eyes were harvested from donors with and without macular degeneration within 2-24 hrs. postmortem. Protocols were developed which permitted dark adaptation of normal human eyes after death and enucleation. Biochemical methods of purifying rod outer segments were optimized and the concentration of rhodopsin and apo-opsin was measured with UV-visible scanning spectroscopy. The presence of apo-opsin was calculated by measuring the difference in the rhodopsin absorption spectra before and after the addition of 11 -cis retinal. A total of 20 normal eyes and 16 eyes from donors with early, intermediate and advanced stages of macular degeneration were included in the final analysis. Dark adaptation was achieved by harvesting whole globes in low light, transferring into dark (light-proof) canisters and dissecting the globes using infrared light and image converters for visualization. Apo-opsin was readily detected in positive controls after the addition of 11 -cis retinal. Normal autopsy eyes showed no evidence of apo-opsin. Eyes with macular degeneration also showed no evidence of apo-opsin, regardless of the severity of disease. Methods have been developed to study dark adaptation in human autopsy eyes. Eyes with age-related macular degeneration do not show a deficiency of 11 -cis retinal or an excess of apo-opsin within rod outer segments.

Deformation of the Normal Monkey Optic Nerve Head Connective Tissue Following Acute IOP Elevation within 3-D Histomorphometric Reconstructions

PubMed Central

Yang, Hongli; Downs, J. Crawford; Sigal, Ian A.; Roberts, Michael D.; Thompson, Hillary; Burgoyne, Claude F.

2010-01-01

Purpose To characterize optic nerve head (ONH) connective tissue deformation following acute (15 or 30 minutes) intraocular pressure (IOP) elevation within six adult normal monkeys using 3-D histomorphometry. Methods Trephinated ONH and peripapillary sclera from both eyes of six monkeys, each perfusion fixed with one eye at IOP 10 mmHg and the other at IOP 30 or 45 mmHg by anterior chamber manometer were serial sectioned, 3-D reconstructed, 3-D delineated and quantified using standard parameters. For each monkey, inter-eye differences (high IOP eye minus IOP 10 eye) for each parameter were calculated and compared by ANOVA and EPIDmax both overall and regionally. EPIDmax deformations for each parameter were defined to be those statistically significant differences that exceeded the maximum physiologic inter-eye difference within six bilaterally normal monkeys of a previous report. Results Regional EPIDmax laminar thinning, posterior bowing of the peripapillary sclera, thinning and expansion of the scleral canal were present in most high IOP eyes and were colocalized in those demonstrating the most deformation. Laminar deformation was minimal and not only posterior but in some cases anterior in the high IOP eyes. No increase in deformation was seen in the IOP-45 versus the IOP-30 eyes. Conclusion ONH connective tissue alterations following acute IOP elevation involve regional thinning, stretching and deformation of the lamina cribrosa and peripapillary sclera which are minimal to modest in magnitude. The time-dependent character of these alterations, as well as their compressive, expansile, and shear effects on the contained axons, astrocytes, laminar and posterior ciliary circulations remain to be determined. PMID:19628739

Microarray-based IgE detection in tears of patients with vernal keratoconjunctivitis.

PubMed

Leonardi, Andrea; Borghesan, Franco; Faggian, Diego; Plebani, Mario

2015-11-01

A specific allergen sensitization can be demonstrated in approximately half of the vernal keratoconjunctivitis (VKC) patients by conventional allergic tests. The measurement of specific IgE in tears using a multiplex allergen microarray may offer advantages to identify local sensitization to a specific allergen. In spring-summer 2011, serum and tears samples were collected from 10 active VKC patients (three females, seven males) and 10 age-matched normal subjects. Skin prick test, symptoms score and full ophthalmological examination were performed. Specific serum and tear IgE were assayed using ImmunoCAP ISAC, a microarray containing 103 components derived from 47 allergens. Normal subjects resulted negative for the presence of specific IgE both in serum and in tears. Of the 10 VKC patients, six resulted positive to specific IgE in serum and/or tears. In three of these six patients, specific IgE was found positive only in tears. Cross-reactivity between specific markers was found in three patients. Grass, tree, mites, animal but also food allergen-specific IgE were found in tears. Conjunctival provocation test performed out of season confirmed the specific local conjunctival reactivity. Multiple specific IgE measurements with single protein allergens using a microarray technique in tear samples are a useful, simple and non-invasive diagnostic tool. ImmunoCAP ISAC detects allergen sensitization at component level and adds important information by defining both cross- and co-sensitization to a large variety of allergen molecules. The presence of specific IgE only in tears of VKC patients reinforces the concept of possible local sensitization. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Retinal cell responses to elevated intraocular pressure: a gene array comparison between the whole retina and retinal ganglion cell layer.

PubMed

Guo, Ying; Cepurna, William O; Dyck, Jennifer A; Doser, Tom A; Johnson, Elaine C; Morrison, John C

2010-06-01

To determine and compare gene expression patterns in the whole retina and retinal ganglion cell layer (RGCL) in a rodent glaucoma model. IOP was unilaterally elevated in Brown Norway rats (N = 26) by injection of hypertonic saline and monitored for 5 weeks. A cDNA microarray was used on whole retinas from one group of eyes with extensive optic nerve injury and on RGCL isolated by laser capture microdissection (LCM) from another group with comparable injury, to determine the significantly up- or downregulated genes and gene categories in both groups. Expression changes of selected genes were examined by quantitative reverse transcription-PCR (qPCR) to verify microarray results. Microarray analysis of the whole retina identified 632 genes with significantly changed expression (335 up, 297 down), associated with 9 upregulated and 3 downregulated biological processes. In contrast, the RGCL microarray yielded 3726 genes with significantly changed expression (2003 up, 1723 down), including 60% of those found in whole retina. Thirteen distinct upregulated biological processes were identified in the RGCL, dominated by protein synthesis. Among 11 downregulated processes, axon extension and dendrite morphogenesis and generation of precursor metabolism and energy were uniquely identified in the RGCL. qPCR confirmed significant changes in 6 selected messages in whole retina and 11 in RGCL. Increased Atf3, the most upregulated gene in the RGCL, was confirmed by immunohistochemistry of RGCs. Isolation of RGCL by LCM allows a more refined detection of gene response to elevated pressure and improves the potential of determining cellular mechanisms in RGCs and their supporting cells that could be targets for enhancing RGC survival.

Parameter estimation for the exponential-normal convolution model for background correction of affymetrix GeneChip data.

PubMed

McGee, Monnie; Chen, Zhongxue

2006-01-01

There are many methods of correcting microarray data for non-biological sources of error. Authors routinely supply software or code so that interested analysts can implement their methods. Even with a thorough reading of associated references, it is not always clear how requisite parts of the method are calculated in the software packages. However, it is important to have an understanding of such details, as this understanding is necessary for proper use of the output, or for implementing extensions to the model. In this paper, the calculation of parameter estimates used in Robust Multichip Average (RMA), a popular preprocessing algorithm for Affymetrix GeneChip brand microarrays, is elucidated. The background correction method for RMA assumes that the perfect match (PM) intensities observed result from a convolution of the true signal, assumed to be exponentially distributed, and a background noise component, assumed to have a normal distribution. A conditional expectation is calculated to estimate signal. Estimates of the mean and variance of the normal distribution and the rate parameter of the exponential distribution are needed to calculate this expectation. Simulation studies show that the current estimates are flawed; therefore, new ones are suggested. We examine the performance of preprocessing under the exponential-normal convolution model using several different methods to estimate the parameters.

Estimation of low-dose radiation-responsive proteins in the absence of genomic instability in normal human fibroblast cells.

PubMed

Yim, Ji-Hye; Yun, Jung Mi; Kim, Ji Young; Nam, Seon Young; Kim, Cha Soon

2017-11-01

Low-dose radiation has various biological effects such as adaptive responses, low-dose hypersensitivity, as well as beneficial effects. However, little is known about the particular proteins involved in these effects. Here, we sought to identify low-dose radiation-responsive phosphoproteins in normal fibroblast cells. We assessed genomic instability and proliferation of fibroblast cells after γ-irradiation by γ-H2AX foci and micronucleus formation analyses and BrdU incorporation assay, respectively. We screened fibroblast cells 8 h after low-dose (0.05 Gy) γ-irradiation using Phospho Explorer Antibody Microarray and validated two differentially expressed phosphoproteins using Western blotting. Cell proliferation proceeded normally in the absence of genomic instability after low-dose γ-irradiation. Phospho antibody microarray analysis and Western blotting revealed increased expression of two phosphoproteins, phospho-NFκB (Ser536) and phospho-P70S6K (Ser418), 8 h after low-dose radiation. Our findings suggest that low-dose radiation of normal fibroblast cells activates the expression of phospho-NFκB (Ser536) and phospho-P70S6K (Ser418) in the absence of genomic instability. Therefore, these proteins may be involved in DNA damage repair processes.

Simultaneous measurement of tear film dynamics using wavefront sensor and optical coherence tomography.

PubMed

Koh, Shizuka; Tung, Cynthia; Aquavella, James; Yadav, Rahul; Zavislan, James; Yoon, Geunyoung

2010-07-01

PURPOSE. To investigate tear film dynamics using simultaneous measurements of ocular aberrations and lower tear meniscus. METHODS. Simultaneous measurements of wavefront aberration and lower tear meniscus were performed for 11 normal eyes and 7 eyes with short tear film break-up time (SBUT) dry eye, with a tear film break-up time shorter than 5 seconds, using a wavefront sensor and an anterior segment optical coherence tomography (OCT). During the measurement, the subjects were instructed to blink every 6 seconds for a total of 30 seconds. From the measured aberration, root mean square (RMS) wavefront error and volume modulation transfer function (vMTF) induced by changes in tear film dynamics were calculated for a 5-mm pupil. Lower tear meniscus height (TMH) and area (TMA) were estimated from the cross-sectional OCT images of lower tear meniscus. RESULTS. There was a positive correlation between RMS and tear meniscus dimensions and a negative correlation between vMTF and tear meniscus in both groups. There were moderate negative correlations between the postblink initial RMS change and baseline TMH (R = -0.61) and TMA (R = -0.54) in SBUT dry eyes that were stronger than in normal eyes (R = -0.37, R = -0.38). CONCLUSIONS. Tear meniscus dimensions increase with RMS over time, and tear quantity before blink has a significant role in maintaining initial optical integrity, especially in SBUT dry eye. Simultaneous measurement of optical quality and tear meniscus has the potential to improve understanding of tear stability in normal eyes and dry eyes.

Eye Dominance Predicts fMRI Signals in Human Retinotopic Cortex

PubMed Central

Mendola, Janine D.; Conner, Ian P.

2009-01-01

There have been many attempts to define eye dominance in normal subjects, but limited consensus exists, and relevant physiological data is scarce. In this study, we consider two different behavioral methods for assignment of eye dominance, and how well they predict fMRI signals evoked by monocular stimulation. Sighting eye dominance was assessed with two standard tests, the Porta Test, and a ‘hole in hand’ variation of the Miles Test. Acuity dominance was tested with a standard eye chart and with a computerized test of grating acuity. We found limited agreement between the sighting and acuity methods for assigning dominance in our individual subjects. We then compared the fMRI response generated by dominant eye stimulation to that generated by non-dominant eye, according to both methods, in 7 normal subjects. The stimulus consisted of a high contrast hemifield stimulus alternating with no stimulus in a blocked paradigm. In separate scans, we used standard techniques to label the borders of visual areas V1, V2, V3, VP, V4, V3A, and MT. These regions of interest (ROIs) were used to analyze each visual area separately. We found that percent change in fMRI BOLD signal was stronger for the dominant eye as defined by the acuity method, and this effect was significant for areas located in the ventral occipital territory (V1v, V2v, VP, V4). In contrast, assigning dominance based on sighting produced no significant interocular BOLD differences. We conclude that interocular BOLD differences in normal subjects exist, and may be predicted by acuity measures. PMID:17194544

Regional Differences in Tear Film Stability and Meibomian Glands in Patients With Aqueous-Deficient Dry Eye.

PubMed

Koh, Shizuka; Ikeda, Chikako; Fujimoto, Hisataka; Oie, Yoshinori; Soma, Takeshi; Maeda, Naoyuki; Nishida, Kohji

2016-07-01

To noninvasively investigate regional differences in tear film stability and meibomian glands in patients with aqueous-deficient dry eye. Forty-nine dry eyes and 31 normal eyes were analyzed. A corneal topographer with a tear film scanning function was used for noninvasive tear film break-up time (NI-TFBUT) measurements and meibomian gland observations. The NI-TFBUT values and location of the first tear film break-up point were recorded in four quadrants. Meibomian gland loss was graded for each eyelid using meiboscores. Lid margin abnormality was scored from zero to four according to the number of existing abnormalities. The NI-TFBUT values and meiboscores were compared between two groups, and regional differences in NI-TFBUT values and meiboscores were analyzed. Also, the correlation between the NI-TFBUT and ocular surface examination results were investigated. The NI-TFBUT values and meiboscores were significantly lower and higher, respectively, for the dry eye group than for the normal group. In the dry eye group, the occurrence rate for first tear film break-up was the highest in the inferior nasal quadrant, and the mean meiboscore was significantly higher for the upper eyelids than for the lower eyelids. The NI-TFBUT and lid margin abnormality scores showed a weak negative correlation, and the NI-TFBUT values and meiboscores showed no correlation. Compared to normal eyes, aqueous-deficient dry eyes show significant regional differences in tear film stability and meibomian glands. Considering these regional differences, the overall observation of the ocular surface, including both upper and lower eyelids, will aid clinicians in understanding this condition better.

Prevalence of Split Nerve Fiber Layer Bundles in Healthy People Imaged with Spectral Domain Optical Coherence Tomography.

PubMed

Gür Güngör, Sirel; Akman, Ahmet; Sarıgül Sezenöz, Almila; Tanrıaşıkı, Gülşah

2016-12-01

The presence of retinal nerve fiber layer (RNFL) split bundles was recently described in normal eyes scanned using scanning laser polarimetry and by histologic studies. Split bundles may resemble RNFL loss in healthy eyes. The aim of our study was to determine the prevalence of nerve fiber layer split bundles in healthy people. We imaged 718 eyes of 359 healthy persons with the spectral domain optical coherence tomography in this cross-sectional study. All eyes had intraocular pressure of 21 mmHg or less, normal appearance of the optic nerve head, and normal visual fields (Humphrey Field Analyzer 24-2 full threshold program). In our study, a bundle was defined as 'split' when there is localized defect not resembling a wedge defect in the RNFL deviation map with a symmetrically divided RNFL appearance on the RNFL thickness map. The classification was performed by two independent observers who used an identical set of reference examples to standardize the classification. Inter-observer consensus was reached in all cases. Bilateral superior split bundles were seen in 19 cases (5.29%) and unilateral superior split was observed in 15 cases (4.16%). In 325 cases (90.52%) there was no split bundle. Split nerve fiber layer bundles, in contrast to single nerve fiber layer bundles, are not common findings in healthy eyes. In eyes with normal optic disc appearance, especially when a superior RNFL defect is observed in RNFL deviation map, the RNLF thickness map and graphs should also be examined for split nerve fiber layer bundles.

Corneal status in primary angle-closure glaucoma with a history of acute attack.

PubMed

Chen, Mei-Ju; Liu, Catherine Jui-Ling; Cheng, Ching-Yu; Lee, Shui-Mei

2012-01-01

The corneal status of patients with primary angle-closure glaucoma (PACG) with a history of acute attack was investigated. This cross-sectional study included 40 eyes of PACG patients with an earlier documented symptomatic acute angle-closure attack (aPACG), 40 uninvolved fellow eyes of aPACG patients (fPACG), 44 eyes of chronic PACG patients without such a history (cPACG), and 50 eyes of age-matched normal participants. All glaucoma patients had patent peripheral iridotomies with adequate intraocular pressure control. The examinations and recorded parameters included visual acuity, intraocular pressure, gonioscopy, vertical cup-to-disc ratio, specular microscopy, central corneal pachymetry, refraction, corneal curvature radius, anterior chamber depth, axial length, and lens thickness measurements, and the presenting intraocular pressure and the duration of acute angle-closure attack for aPACG eyes. The mean endothelial cell density was 2271±80 cells/mm(2) in aPACG, 2458±79 cells/mm(2) in fPACG, 2379±50 cells/mm(2) in cPACG, and 2559±45 cells/mm(2) in controls. The aPACG eyes had significantly lower endothelial cell density compared with normal eyes (P=0.002). There was no significant difference in endothelial cell density of aPACG eyes compared with fPACG or cPACG eyes. Multivariate analysis showed the duration of the acute attack was the only factor independently associated with corneal endothelial density of aPACG eyes. The mean central corneal thickness of aPACG (549±32 μm) did not differ significantly from control eyes (552±27 μm), cPACG (557±32 μm), and fPACG (553±31 μm) (P=0.911, 0.274, and 0.725, respectively). Corneal curvature radius of aPACG eyes was not significantly different from that of the comparison groups (all P>0.05). Corneal endothelial cell density was significantly reduced in aPACG eyes compared with normal eyes. No significant difference in endothelial cell density of aPACG eyes was noted when compared with fPACG or cPACG eyes. Corneal endothelial cell density was negatively associated with the duration of the acute attack, but was not associated with demographic and biometric characteristics. Central corneal thickness and corneal curvature radius were not associated with an earlier acute angle-closure attack.

Simultaneous subtyping and pathotyping of avian influenza viruses in chickens in Taiwan using reverse transcription loop-mediated isothermal amplification and microarray

PubMed Central

WANG, Lih-Chiann; HUANG, Dean; CHEN, Hui-Wen

2016-01-01

The H6N1 avian influenza virus has circulated in Taiwan for more than 40 years. The sporadic activity of low pathogenic H5N2 virus has been noted since 2003, and highly pathogenic H5N2 avian influenza virus has been detected since 2008. Ressortant viruses between H6N1 and H5N2 viruses have become established and enzootic in chickens throughout Taiwan. Outbreaks caused by Novel highly pathogenic H5 avian influenza viruses whose HA genes were closely related to that of the H5N8 virus isolated from ducks in Korea in 2014 were isolated from outbreaks in Taiwan since early 2015. The avian influenza virus infection status is becoming much more complicated in chickens in Taiwan. This necessitates a rapid and simple approach to detect and differentiate the viruses that prevail. H6N1, H5N2 and novel H5 viruses were simultaneously subtyped and pathotyped in this study using reverse transcription loop-mediated isothermal amplification and microarray, with detection limits of 10°, 101 and 10° viral copy numbers, respectively. The microarray signals were read by the naked eye with no expensive equipment needed. The method developed in this study could greatly improve avian influenza virus surveillance efficiency. PMID:27086860

Distinct Circuits for Recovery of Eye Dominance and Acuity in Murine Amblyopia.

PubMed

Stephany, Céleste-Élise; Ma, Xiaokuang; Dorton, Hilary M; Wu, Jie; Solomon, Alexander M; Frantz, Michael G; Qiu, Shenfeng; McGee, Aaron W

2018-05-24

Degrading vision by one eye during a developmental critical period yields enduring deficits in both eye dominance and visual acuity. A predominant model is that "reactivating" ocular dominance (OD) plasticity after the critical period is required to improve acuity in amblyopic adults. However, here we demonstrate that plasticity of eye dominance and acuity are independent and restricted by the nogo-66 receptor (ngr1) in distinct neuronal populations. Ngr1 mutant mice display greater excitatory synaptic input onto both inhibitory and excitatory neurons with restoration of normal vision. Deleting ngr1 in excitatory cortical neurons permits recovery of eye dominance but not acuity. Reciprocally, deleting ngr1 in thalamus is insufficient to rectify eye dominance but yields improvement of acuity to normal. Abolishing ngr1 expression in adult mice also promotes recovery of acuity. Together, these findings challenge the notion that mechanisms for OD plasticity contribute to the alterations in circuitry that restore acuity in amblyopia. Copyright © 2018 Elsevier Ltd. All rights reserved.

Latent binocular function in amblyopia.

PubMed

Chadnova, Eva; Reynaud, Alexandre; Clavagnier, Simon; Hess, Robert F

2017-11-01

Recently, psychophysical studies have shown that humans with amblyopia do have binocular function that is not normally revealed due to dominant suppressive interactions under normal viewing conditions. Here we use magnetoencephalography (MEG) combined with dichoptic visual stimulation to investigate the underlying binocular function in humans with amblyopia for stimuli that, because of their temporal properties, would be expected to bypass suppressive effects and to reveal any underlying binocular function. We recorded contrast response functions in visual cortical area V1 of amblyopes and normal observers using a steady state visually evoked responses (SSVER) protocol. We used stimuli that were frequency-tagged at 4Hz and 6Hz that allowed identification of the responses from each eye and were of a sufficiently high temporal frequency (>3Hz) to bypass suppression. To characterize binocular function, we compared dichoptic masking between the two eyes in normal and amblyopic participants as well as interocular phase differences in the two groups. We observed that the primary visual cortex responds less to the stimulation of the amblyopic eye compared to the fellow eye. The pattern of interaction in the amblyopic visual system however was not significantly different between the amblyopic and fellow eyes. However, the amblyopic suppressive interactions were lower than those observed in the binocular system of our normal observers. Furthermore, we identified an interocular processing delay of approximately 20ms in our amblyopic group. To conclude, when suppression is greatly reduced, such as the case with our stimulation above 3Hz, the amblyopic visual system exhibits a lack of binocular interactions. Copyright © 2017 Elsevier Ltd. All rights reserved.

Nerve fibre layer analysis with GDx with a variable corneal compensator in patients with multiple sclerosis.

PubMed

Della Mea, Giovanni; Bacchetti, Sonia; Zeppieri, Marco; Brusini, Paolo; Cutuli, Daniela; Gigli, Gian Luigi

2007-01-01

To evaluate the ability of GDx with variable corneal compensator (VCC) compared to visual-evoked potentials (VEPs) and standard automated perimetry (SAP) in the detection of early optic nerve damage in patients with multiple sclerosis (MS). 46 eyes of 23 MS patients were included. Ten of them had a history of acute retrobulbar optic neuritis. A control group of 20 normal subjects was also included. All subjects underwent a complete ophthalmological examination and testing with SAP, GDx VCC and VEPs. 19 eyes (41.3%) were abnormal with GDx VCC compared to 38 eyes (82.6%) with SAP and 31 (64.4%) with VEPs. In the optic neuritis group, 9 eyes (69.2%) had optic nerve pallor; SAP was abnormal in 8 of these eyes (61.5%) while VEPs and GDx VCC were abnormal in 6 eyes (46.1%). 2/20 eyes (10.0%) in the control group gave a false-positive abnormal result with SAP. GDx VCC and VEP were normal for all the eyes in the control group. GDx VCC is less able to detect early defects in MS patients compared to the currently used standard techniques of SAP and VEPs. Copyright (c) 2007 S. Karger AG, Basel.

Factors influencing flap and INTACS decentration after femtosecond laser application in normal and keratoconic eyes.

PubMed

Ertan, Aylin; Karacal, Humeyra

2008-10-01

To compare accuracy of LASIK flap and INTACS centration following femtosecond laser application in normal and keratoconic eyes. This is a retrospective case series comprising 133 eyes of 128 patients referred for refractive surgery. All eyes were divided into two groups according to preoperative diagnosis: group 1 (LASIK group) comprised 74 normal eyes of 72 patients undergoing LASIK with a femtosecond laser (IntraLase), and group 2 (INTACS group) consisted of 59 eyes of 39 patients with keratoconus for whom INTACS were implanted using a femtosecond laser (IntraLase). Decentration of the LASIK flap and INTACS was analyzed using Pentacam. Temporal decentration was 612.56 +/- 384.24 microm (range: 30 to 2120 microm) in the LASIK group and 788.33 +/- 500.34 microm (range: 30 to 2450 microm) in the INTACS group. A statistically significant difference was noted between the groups in terms of decentration (P < .05). Regression analysis showed that the amount of decentration of the LASIK flap and INTACS correlated with the central corneal thickness in the LASIK group and preoperative sphere and cylinder in the INTACS group, respectively. Decentration with the IntraLase occurred in most cases, especially in keratoconic eyes. The applanation performed for centralization during IntraLase application may flatten and shift the pupil center, and thus cause decentralization of the LASIK flap and INTACS. Central corneal thickness in the LASIK group and preoperative sphere and cylinder in the INTACS group proved to be statistically significant parameters associated with decentration.

Stimulation of pontine reticular formation in monkeys with strabismus.

PubMed

Walton, Mark M G; Ono, Seiji; Mustari, Michael J

2013-10-29

Saccade disconjugacy in strabismus could result from any of a number of factors, including abnormalities of eye muscles, the plant, motoneurons, near response cells, or atypical tuning of neurons in saccade-related areas of the brain. This study was designed to investigate the possibility that saccade disconjugacy in strabismus is associated with abnormalities in paramedian pontine reticular formation (PPRF). We applied microstimulation to 22 sites in PPRF and 20 sites in abducens nucleus in three rhesus macaque monkeys (one normal, one esotrope, and one exotrope). When mean velocity was compared between the two eyes, a slight difference was found for 1/5 sites in the normal animal. Significant differences were found for 5/6 sites in an esotrope and 10/11 sites in an exotrope. For five sites in the strabismic monkeys, the directions of evoked movements differed by more than 40° between the two eyes. When stimulation was applied to abducens nucleus (20 sites), the ipsilateral eye moved faster for 4/6 sites in the normal animal and all nine sites in the esotrope. For the exotrope, however, the left eye always moved faster, even for three sites on the right side. For the strabismic animals, stimulation of abducens nucleus often caused a different eye to move faster than stimulation of PPRF. These data suggest that PPRF is organized at least partly monocularly in strabismus and that disconjugate saccades are at least partly a consequence of unbalanced saccadic commands being sent to the two eyes.

The quantitative measurements of foveal avascular zone using optical coherence tomography angiography in normal volunteers.

PubMed

Ghassemi, Fariba; Mirshahi, Reza; Bazvand, Fatemeh; Fadakar, Kaveh; Faghihi, Houshang; Sabour, Siamak

2017-12-01

To provide normative data of foveal avascular zone (FAZ) and thickness. In this cross-sectional study both eyes of each normal subject were scanned with optical coherence tomography angiography (OCTA) for foveal superficial and deep avascular zone (FAZ) and central foveal thickness (CFT) and parafoveal thickness (PFT). Out of a total of 224 eyes of 112 volunteers with a mean age of 37.03 (12-67) years, the mean superficial FAZ area was 0.27 mm 2 , and deep FAZ area was 0.35 mm 2 ( P  < 0.001), with no difference between both eyes. Females had a larger superficial (0.32 ± 0.11 mm 2 versus 0.23 ± 0.09 mm 2 ) and deep FAZ (0.40 ± 0.14 mm 2 versus 0.31 ± 0.10 mm 2 ) ( P  < 0.001) than males. By multivariate linear regression analysis, in normal eyes, superficial FAZ area varied significantly with the gender, CFT, and deep FAZ. Deep FAZ varied with the gender and CFT. The gender and CFT influence the size of normal superficial and deep FAZ of capillary network.

Eye examination in the cat: Step-by-step approach and common findings.

PubMed

Stiles, Jean; Kimmitt, Beth

2016-09-01

The ability to perform a complete eye examination in the cat is critically important for patients with an ocular disorder or a systemic disease, as well as for the geriatric cat. Cats may need short breaks between portions of the eye exam in order to minimize stress. For the clinician, use of ophthalmic equipment and interpretation of normal vs abnormal findings may take some practice in order to develop proficiency. This review is aimed at veterinary practitioners and outlines all the steps and equipment necessary to perform a complete ophthalmic examination in the cat. Although some specialized equipment is required, a complete eye exam can be performed with a modest investment in equipment and supplies. This article draws on published references for normal parameters measured in the feline eye exam, as well as the experience of the authors. © The Author(s) 2016.

The perceptual consequences of interocular suppression in amblyopia.

PubMed

Maehara, Goro; Thompson, Benjamin; Mansouri, Behzad; Farivar, Reza; Hess, Robert F

2011-11-21

It is known that information from an amblyopic eye can be strongly suppressed when both eyes are open. The authors investigated the way in which suppression influences the relative perception of suprathreshold contrast and luminance between a person's eyes under dichoptic viewing conditions. Stimuli consisted of four patches of luminance or four patches containing gratings. Two patches were presented to each eye. Ten amblyopes with mild suppression (six strabismic, three anisometropic and strabismic, and one deprivation; mean age, 34.5 years) and three control observers with normal vision (mean age, 33.0 years) matched the appearance of the stimuli presented to each eye. The match involved manipulation of either luminance or contrast. Amblyopes with mild suppression decreased stimulus luminance in the fellow fixing eye or increased luminance in the amblyopic eye to achieve a match (mean matching luminance, 21.1 and 39.6 cd/m(2) for the fellow fixing eye and the amblyopic eye, respectively; standard luminance, 30 cd/m(2)). This interocular mismatch was also observed when luminance was variable and contrast was kept constant (mean matching luminance, 22.8 cd/m(2) for the fellow fixing eye). On the other hand, the amblyopic eye showed no loss of perceived contrast. There was little or no mismatch between the two eyes of control participants with normal binocular vision. Amblyopes have monocular deficits in contrast perception but dichoptic deficits in luminance perception, suggesting that suppression in its mild form involves luminance processing.

Vision impairment and major causes of vision loss impacts on vision-specific functioning independent of socioeconomic factors.

PubMed

Chiang, Peggy P C; Zheng, Yingfeng; Wong, Tien Y; Lamoureux, Ecosse L

2013-02-01

To quantify the eye disease-specific impact of unilateral and bilateral vision impairment (VI) on vision-specific functioning (VF). The Singapore Indian Eye population-based study. Ethnic Indians older than 40 years of age living in Singapore. Participants underwent standardized ophthalmic assessments for VI and blindness, defined using presenting visual acuity (United States definition). Sociodemographic data were recorded using a standardized questionnaire. Rasch analysis was used to validate the Visual Function Index 11 and to determine its psychometric properties. The major causes of VI (i.e., cataract, refractive error, age-related macular degeneration, diabetic retinopathy [DR], and glaucoma) were determined by ophthalmologists on examination. Multivariate linear regression analysis was performed to assess the impact of VI on the overall VF Rasch score. Vision-specific functioning. Three thousand three hundred ninety-six persons were analyzed. Participants with VI had a systematic reduction in VF score compared with those with normal vision in both eyes, ranging from -11.2% normal vision in one eye and low vision in the other eye (95% confidence interval [CI], -12.2% to -10.3%; P<0.001), to -12.7% blindness in one eye and normal vision in the other eye (CI, -15.1% to -10.4%; P<0.001), to -19.4% low vision in both eyes (CI, -20.8% to -18.1%; P<0.001), to -52.9% blindness in one eye and low vision in other eye (CI, -55.3% to -50.4%; P<0.001), to -77.2% blindness in both eyes (CI, -82.4% to 72.0%; P<0.001). The impact of VI on VF score varied across different major causes of vision loss, regardless of socioeconomic factors. Vision impairment attributed to cataract in one or both eyes had a significant decrease in VF score by 17.7% and 22.3%, respectively, compared with those with normal vision in both eyes (P<0.001). The impact of unilateral and bilateral VI on VF score was greater in participants with glaucoma (32.2% in unilateral cases and 35.9% in bilateral cases; P<0.001) and DR (29.4% in unilateral cases and 33.3% in bilateral cases; P<0.001). Vision impairment and major age-related eye diseases such as cataract, DR, and glaucoma are associated significantly with worse deterioration in VF, regardless of education level, literacy adequacy, or immigration pattern. Glaucoma and DR seemed to have a greater negative impact on VF score compared with cataract. This study highlights the importance of disease-specific interventions in reducing the adverse impact of VI on daily activities. Copyright © 2013 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

MAGMA: analysis of two-channel microarrays made easy.

PubMed

Rehrauer, Hubert; Zoller, Stefan; Schlapbach, Ralph

2007-07-01

The web application MAGMA provides a simple and intuitive interface to identify differentially expressed genes from two-channel microarray data. While the underlying algorithms are not superior to those of similar web applications, MAGMA is particularly user friendly and can be used without prior training. The user interface guides the novice user through the most typical microarray analysis workflow consisting of data upload, annotation, normalization and statistical analysis. It automatically generates R-scripts that document MAGMA's entire data processing steps, thereby allowing the user to regenerate all results in his local R installation. The implementation of MAGMA follows the model-view-controller design pattern that strictly separates the R-based statistical data processing, the web-representation and the application logic. This modular design makes the application flexible and easily extendible by experts in one of the fields: statistical microarray analysis, web design or software development. State-of-the-art Java Server Faces technology was used to generate the web interface and to perform user input processing. MAGMA's object-oriented modular framework makes it easily extendible and applicable to other fields and demonstrates that modern Java technology is also suitable for rather small and concise academic projects. MAGMA is freely available at www.magma-fgcz.uzh.ch.

Comparative transcriptional profiling of human Merkel cells and Merkel cell carcinoma.

PubMed

Mouchet, Nicolas; Coquart, Nolwenn; Lebonvallet, Nicolas; Le Gall-Ianotto, Christelle; Mogha, Ariane; Fautrel, Alain; Boulais, Nicholas; Dréno, Brigitte; Martin, Ludovic; Hu, Weiguo; Galibert, Marie-Dominique; Misery, Laurent

2014-12-01

Merkel cell carcinoma is believed to be derived from Merkel cells after infection by Merkel cell polyomavirus (MCPyV) and other poorly understood events. Transcriptional profiling using cDNA microarrays was performed on cells from MCPy-negative and MCPy-positive Merkel cell carcinomas and isolated normal Merkel cells. This microarray revealed numerous significantly upregulated genes and some downregulated genes. The extensive list of genes that were identified in these experiments provides a large body of potentially valuable information of Merkel cell carcinoma carcinogenesis and could represent a source of potential targets for cancer therapy. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Theoretical investigation of aberrations upon ametropic human eyes

NASA Astrophysics Data System (ADS)

Tan, Bo; Chen, Ying-Ling; Lewis, J. W. L.; Baker, Kevin

2003-11-01

The human eye aberrations are important for visual acuity and ophthalmic diagnostics and surgical procedures. Reported monochromatic aberration data of the normal 20/20 human eyes are scarce. There exist even fewer reports of the relation between ametropic conditions and aberrations. We theoretically investigate the monochromatic and chromatic aberrations of human eyes for refractive errors of -10 to +10 diopters. Schematic human eye models are employed using optical design software for axial, index, and refractive types of ametropia.

Effects of monocular viewing and eye dominance on spatial attention.

PubMed

Roth, Heidi L; Lora, Andrea N; Heilman, Kenneth M

2002-09-01

Observations in primates and patients with unilateral spatial neglect have suggested that patching of the eye ipsilateral to the injury and contralateral to the neglected space can sometimes improve attention to the neglected space. Investigators have generally attributed the effects of monocular eye patching to activation of subcortical centers that interact with cortical attentional systems. Eye patching is thought to produce preferential activation of attentional systems contralateral to the viewing eye. In this study we examined the effect of monocular eye patching on attentional biases in normal subjects. When normal subjects bisect vertical (radial) lines using both eyes, they demonstrate a far attentional bias, misbisecting lines away from their body. In a monocular viewing experiment, we found that the majority of subjects, who were right eye dominant, had relatively nearer bisections and a diminished far bias when they used their right eye (left eye covered) compared with when they used their left eye (right eye covered). The smaller group of subjects who were left eye dominant had relatively nearer bisections and a diminished far bias when they used their left eye compared with when they used their right eye. In the hemispatial placement experiment, we directly manipulated hemispheric engagement by having subjects perform the same task in right and left hemispace. We found that right eye dominant subjects had a diminished far bias in right hemispace relative to left hemispace. Left eye dominant subjects showed the opposite pattern and had a diminished far bias in left hemispace. For both groups, spatial presentation affected performance more for the non-dominant eye. The results suggest that monocular viewing is associated with preferential activation of attentional systems in the contralateral hemisphere, and that the right hemisphere (at least in right eye dominant subjects) is biased towards far space. Finally, the results suggest that the poorly understood phenomenon of eye dominance may be related to hemispheric specialization for visual attention.

An experimental loop design for the detection of constitutional chromosomal aberrations by array CGH

PubMed Central

2009-01-01

Background Comparative genomic hybridization microarrays for the detection of constitutional chromosomal aberrations is the application of microarray technology coming fastest into routine clinical application. Through genotype-phenotype association, it is also an important technique towards the discovery of disease causing genes and genomewide functional annotation in human. When using a two-channel microarray of genomic DNA probes for array CGH, the basic setup consists in hybridizing a patient against a normal reference sample. Two major disadvantages of this setup are (1) the use of half of the resources to measure a (little informative) reference sample and (2) the possibility that deviating signals are caused by benign copy number variation in the "normal" reference instead of a patient aberration. Instead, we apply an experimental loop design that compares three patients in three hybridizations. Results We develop and compare two statistical methods (linear models of log ratios and mixed models of absolute measurements). In an analysis of 27 patients seen at our genetics center, we observed that the linear models of the log ratios are advantageous over the mixed models of the absolute intensities. Conclusion The loop design and the performance of the statistical analysis contribute to the quick adoption of array CGH as a routine diagnostic tool. They lower the detection limit of mosaicisms and improve the assignment of copy number variation for genetic association studies. PMID:19925645

hemaClass.org: Online One-By-One Microarray Normalization and Classification of Hematological Cancers for Precision Medicine.

PubMed

Falgreen, Steffen; Ellern Bilgrau, Anders; Brøndum, Rasmus Froberg; Hjort Jakobsen, Lasse; Have, Jonas; Lindblad Nielsen, Kasper; El-Galaly, Tarec Christoffer; Bødker, Julie Støve; Schmitz, Alexander; H Young, Ken; Johnsen, Hans Erik; Dybkær, Karen; Bøgsted, Martin

2016-01-01

Dozens of omics based cancer classification systems have been introduced with prognostic, diagnostic, and predictive capabilities. However, they often employ complex algorithms and are only applicable on whole cohorts of patients, making them difficult to apply in a personalized clinical setting. This prompted us to create hemaClass.org, an online web application providing an easy interface to one-by-one RMA normalization of microarrays and subsequent risk classifications of diffuse large B-cell lymphoma (DLBCL) into cell-of-origin and chemotherapeutic sensitivity classes. Classification results for one-by-one array pre-processing with and without a laboratory specific RMA reference dataset were compared to cohort based classifiers in 4 publicly available datasets. Classifications showed high agreement between one-by-one and whole cohort pre-processsed data when a laboratory specific reference set was supplied. The website is essentially the R-package hemaClass accompanied by a Shiny web application. The well-documented package can be used to run the website locally or to use the developed methods programmatically. The website and R-package is relevant for biological and clinical lymphoma researchers using affymetrix U-133 Plus 2 arrays, as it provides reliable and swift methods for calculation of disease subclasses. The proposed one-by-one pre-processing method is relevant for all researchers using microarrays.

An experimental loop design for the detection of constitutional chromosomal aberrations by array CGH.

PubMed

Allemeersch, Joke; Van Vooren, Steven; Hannes, Femke; De Moor, Bart; Vermeesch, Joris Robert; Moreau, Yves

2009-11-19

Comparative genomic hybridization microarrays for the detection of constitutional chromosomal aberrations is the application of microarray technology coming fastest into routine clinical application. Through genotype-phenotype association, it is also an important technique towards the discovery of disease causing genes and genomewide functional annotation in human. When using a two-channel microarray of genomic DNA probes for array CGH, the basic setup consists in hybridizing a patient against a normal reference sample. Two major disadvantages of this setup are (1) the use of half of the resources to measure a (little informative) reference sample and (2) the possibility that deviating signals are caused by benign copy number variation in the "normal" reference instead of a patient aberration. Instead, we apply an experimental loop design that compares three patients in three hybridizations. We develop and compare two statistical methods (linear models of log ratios and mixed models of absolute measurements). In an analysis of 27 patients seen at our genetics center, we observed that the linear models of the log ratios are advantageous over the mixed models of the absolute intensities. The loop design and the performance of the statistical analysis contribute to the quick adoption of array CGH as a routine diagnostic tool. They lower the detection limit of mosaicisms and improve the assignment of copy number variation for genetic association studies.

2q37 Deletion syndrome confirmed by high-resolution cytogenetic analysis

PubMed Central

Cho, Eun-Kyung; Kim, Jinsup; Yang, Aram; Jin, Dong-Kyu

2017-01-01

Chromosome 2q37 deletion syndrome is a rare chromosomal disorder characterized by mild to moderate developmental delay, brachydactyly of the third to fifth digits or toes, short stature, obesity, hypotonia, a characteristic facial appearance, and autism spectrum disorder. Here, we report on a patient with 2q37 deletion presenting with dilated cardiomyopathy (DCMP). Congenital heart malformations have been noted in up to 20% of patients with 2q37 deletions. However, DCMP has not been reported in 2q37 deletion patients previously. The patient exhibited the characteristic facial appearance (a flat nasal bridge, deep-set eyes, arched eyebrows, and a thin upper lip), developmental delay, mild mental retardation, peripheral nerve palsy, and Albright hereditary osteodystrophy (AHO)-like phenotypes (short stature and brachydactyly). Conventional chromosomal analysis results were normal; however, microarray-based comparative genomic hybridization revealed terminal deletion at 2q37.1q37.3. In addition, the patient was confirmed to have partial growth hormone (GH) deficiency and had shown a significant increase in growth rate after substitutive GH therapy. Chromosome 2q37 deletion syndrome should be considered in the differential diagnosis of patients presenting with AHO features, especially in the presence of facial dysmorphism. When patients are suspected of having a 2q37 deletion, high-resolution cytogenetic analysis is recommended. PMID:28690993

A Maternal Influence on Reading the Mind in the Eyes Mediated by Executive Function: Differential Parental Influences on Full and Half-Siblings

PubMed Central

Ragsdale, Gillian; Foley, Robert A.

2011-01-01

Background Parent-of-origin effects have been found to influence the mammalian brain and cognition and have been specifically implicated in the development of human social cognition and theory of mind. The experimental design in this study was developed to detect parent-of-origin effects on theory of mind, as measured by the ‘Reading the mind in the eyes’ (Eyes) task. Eyes scores were also entered into a principal components analysis with measures of empathy, social skills and executive function, in order to determine what aspect of theory of mind Eyes is measuring. Methodology/Principal Findings Maternal and paternal influences on Eyes scores were compared using correlations between pairs of full (70 pairs), maternal (25 pairs) and paternal siblings (15 pairs). Structural equation modelling supported a maternal influence on Eyes scores over the normal range but not low-scoring outliers, and also a sex-specific influence on males acting to decrease male Eyes scores. It was not possible to differentiate between genetic and environmental influences in this particular sample because maternal siblings tended to be raised together while paternal siblings were raised apart. The principal components analysis found Eyes was associated with measures of executive function, principally behavioural inhibition and attention, rather than empathy or social skills. Conclusions/Significance In conclusion, the results suggest a maternal influence on Eye scores in the normal range and a sex-specific influence acting to reduce scores in males. This influence may act via aspects of executive function such as behavioural inhibition and attention. There may be different influences acting to produce the lowest Eyes scores which implies that the heratibility and/or maternal influence on poor theory of mind skills may be qualitatively different to the influence on the normal range. PMID:21850264

Straightening the Eyes Doesn't Rebalance the Brain

PubMed Central

Zhou, Jiawei; Wang, Yonghua; Feng, Lixia; Wang, Jiafeng; Hess, Robert F.

2017-01-01

Surgery to align the two eyes is commonly used in treating strabismus. However, the role of strabismic surgery on patients' binocular visual processing is not yet fully understood. In this study, we asked two questions: (1) Does realigning the eyes by strabismic surgery produce an immediate benefit to patients' sensory eye balance? (2) If not, is there a subsequent period of “alignment adaptation” akin to refractive adaptation where sensory benefits to binocular function accrue? Seventeen patients with strabismus (mean age: 17.06 ± 5.16 years old) participated in our experiment. All participants had normal or corrected to normal visual acuity (LogMAR < 0.10) in the two eyes. We quantitatively measured their sensory eye balance before and after surgery using a binocular phase combination paradigm. For the seven patients whose sensory eye balance was measured before surgery, we found no significant change [t(6) = −0.92; p = 0.39] in the sensory eye balance measured 0.5–1 months after the surgery, indicating that the surgical re-alignment didn't by itself produce any immediate benefit for sensory eye balance. To answer the second question, we measured 16 patients' sensory eye balance at around 5–12 months after their eyes had been surgically re-aligned and compared this with our measurements 0.5–1 months after surgery. We found no significant change [t(15) = −0.89; p = 0.39] in sensory eye balance 5–12 months after the surgery. These results suggest that strabismic surgery while being necessary is not itself sufficient for re-establishing balanced sensory eye dominance. PMID:28955214

Central Connections of the Lacrimal Functional Unit.

PubMed

Willshire, Catherine; Buckley, Roger J; Bron, Anthony J

2017-08-01

To study the contribution of each eye to the reflex tear response, after unilateral and bilateral topical anesthesia. A closed-eye, modified Schirmer test was performed bilaterally in 8 normal subjects, in a controlled environment chamber set to 23°C, 45% relative humidity, and 0.08 m/s airflow. Eye drops were instilled into each eye 10 minutes before the Schirmer test. Experiments were as follows: 1) bilateral saline (control), 2) unilateral anesthesia (ipsilateral anesthetic; contralateral saline), and 3) bilateral anesthesia. There was no difference in between-eye wetting lengths in the saline control eyes (P = 0.394) or the bilaterally anesthetized eyes (P = 0.171). The wetting length was reduced in both eyes after bilateral anesthesia compared with saline controls (P = 0.001; P ≤ 0.0005). After unilateral anesthesia, the wetting length was reduced in the anesthetized eye compared with its saline control by 51.4% (P ≤ 0.0005) and compared with its fellow, unanesthetized eye (P = 0.005). The fellow eye value was also reduced compared with its saline control (P = 0.06). The wetting length was reduced by topical anesthesia, when instilled bilaterally and ipsilaterally. The latter response implies an ipsilateral, reflex sensory drive to lacrimal secretion. In the unanesthetized fellow eye, the reduction compared with its saline control was not quite significant. This implies a relative lack of central, sensory, reflex cross-innervation, although the possibility cannot entirely be ruled out. These results are relevant to the possibility of reflex lacrimal compensation from a normal fellow eye, in cases of unilateral corneal anesthesia.

Pilot Study: The Role of the Hemispheric Lateralization in Mental Disorders by Use of the Limb (Eye, Hand, Foot) Dominance

PubMed Central

Goodarzi, Naser; Dabbaghi, Parviz; Valipour, Habib; Vafadari, Behnam

2015-01-01

Introduction: Based on the previous studies, we know that the hemispheric lateralization defects, increase the probability of psychological disorders. We also know that dominant limb is controlled by dominant hemisphere and limb preference is used as an indicator for hemisphere dominance. In this study we attempted to explore the hemispheric dominance by the use of three limbs (hand, foot and eye). Methods: We performed this survey on two samples, psychiatric patients compared with normal population. For this purpose, knowing that the organ dominance is stabilized in adolescence, and age has no effect on the people above 15, we used 48 high school girls and 65 boys as the final samples of normal population. The patient group included 57 male and 26 female who were chronic psychiatric patients. Results: The result shows that left-eye dominance is more in patients than the normal group (P=0.000) but the handedness and footedness differences are not significance. In psychotic, bipolar and depressive disorders, eye dominance had significant difference (P=0.018). But this is not true about hand and foot dominance. Discussion: Our findings proved that generally in psychiatric patients, left-eye dominance is more common, left-eye dominance is also more in psychotic and depressive disorders. It is less common in bipolar disorders. PMID:27307954

Corneal endothelial cell density and morphology in normal Iranian eyes

PubMed Central

Hashemian, Mohammad Nasser; Moghimi, Sasan; Fard, Masood Aghsaie; Fallah, Mohammad Reza; Mansouri, Mohammad Reza

2006-01-01

Background We describe corneal endothelial cell density and morphology in normal Iranian eyes and compare endothelial cell characteristics in the Iranian population with data available in the literature for American and Indian populations. Methods Specular microscopy was performed in 525 eyes of normal Iranian people aged 20 to 85 years old. The studied parameters including mean endothelial cell density (MCD), mean cell area (MCA) and coefficient of variation (CV) in cell area were analyzed in all of the 525 eyes. Results MCD was 1961 ± 457 cell/mm2 and MCA was 537.0 ± 137.4 μm2. There was no statistically significant difference in MCD, MCA and CV between genders (Student t-test, P = 0.85, P = 0.97 and P = 0.15 respectively). There was a statistically significant decrease in MCD with age (P < 0.001, r = -0.64). The rate of cell loss was 0.6% per year. There was also a statistically significant increase in MCA (P < 0.001,r = 0.56) and CV (P < 0.001, r = 0.30) from 20 to 85 years of age. Conclusion The first normative data for the endothelium of Iranian eyes seems to confirm that there are no differences in MCD, MCA and CV between genders. Nevertheless, the values obtained in Iranian eyes seem to be different to those reported by the literature in Indian and American populations. PMID:16519812

Corneal endothelial cell density and morphology in normal Iranian eyes.

PubMed

Hashemian, Mohammad Nasser; Moghimi, Sasan; Fard, Masood Aghsaie; Fallah, Mohammad Reza; Mansouri, Mohammad Reza

2006-03-06

We describe corneal endothelial cell density and morphology in normal Iranian eyes and compare endothelial cell characteristics in the Iranian population with data available in the literature for American and Indian populations. Specular microscopy was performed in 525 eyes of normal Iranian people aged 20 to 85 years old. The studied parameters including mean endothelial cell density (MCD), mean cell area (MCA) and coefficient of variation (CV) in cell area were analyzed in all of the 525 eyes. MCD was 1961 +/- 457 cell/mm2 and MCA was 537.0 +/- 137.4 microm2. There was no statistically significant difference in MCD, MCA and CV between genders (Student t-test, P = 0.85, P = 0.97 and P = 0.15 respectively). There was a statistically significant decrease in MCD with age (P < 0.001, r = -0.64). The rate of cell loss was 0.6% per year. There was also a statistically significant increase in MCA (P < 0.001,r = 0.56) and CV (P < 0.001, r = 0.30) from 20 to 85 years of age. The first normative data for the endothelium of Iranian eyes seems to confirm that there are no differences in MCD, MCA and CV between genders. Nevertheless, the values obtained in Iranian eyes seem to be different to those reported by the literature in Indian and American populations.

Segmental Duplications and Copy-Number Variation in the Human Genome

PubMed Central

Sharp, Andrew J. ; Locke, Devin P. ; McGrath, Sean D. ; Cheng, Ze ; Bailey, Jeffrey A. ; Vallente, Rhea U. ; Pertz, Lisa M. ; Clark, Royden A. ; Schwartz, Stuart ; Segraves, Rick ; Oseroff, Vanessa V. ; Albertson, Donna G. ; Pinkel, Daniel ; Eichler, Evan E. 

2005-01-01

The human genome contains numerous blocks of highly homologous duplicated sequence. This higher-order architecture provides a substrate for recombination and recurrent chromosomal rearrangement associated with genomic disease. However, an assessment of the role of segmental duplications in normal variation has not yet been made. On the basis of the duplication architecture of the human genome, we defined a set of 130 potential rearrangement hotspots and constructed a targeted bacterial artificial chromosome (BAC) microarray (with 2,194 BACs) to assess copy-number variation in these regions by array comparative genomic hybridization. Using our segmental duplication BAC microarray, we screened a panel of 47 normal individuals, who represented populations from four continents, and we identified 119 regions of copy-number polymorphism (CNP), 73 of which were previously unreported. We observed an equal frequency of duplications and deletions, as well as a 4-fold enrichment of CNPs within hotspot regions, compared with control BACs (P < .000001), which suggests that segmental duplications are a major catalyst of large-scale variation in the human genome. Importantly, segmental duplications themselves were also significantly enriched >4-fold within regions of CNP. Almost without exception, CNPs were not confined to a single population, suggesting that these either are recurrent events, having occurred independently in multiple founders, or were present in early human populations. Our study demonstrates that segmental duplications define hotspots of chromosomal rearrangement, likely acting as mediators of normal variation as well as genomic disease, and it suggests that the consideration of genomic architecture can significantly improve the ascertainment of large-scale rearrangements. Our specialized segmental duplication BAC microarray and associated database of structural polymorphisms will provide an important resource for the future characterization of human genomic disorders. PMID:15918152

Blinking

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... to prevent harmful substances from getting in the eyes. During the normal course of a day, a ... of 15 times a minute to keep the eyes healthy. The lacrimal gland provides lubricating fluid for ...

Effects of eye rubbing on the levels of protease, protease activity and cytokines in tears: relevance in keratoconus.

PubMed

Balasubramanian, Sivaraman A; Pye, David C; Willcox, Mark D P

2013-03-01

Proteases, protease activity and inflammatory molecules in tears have been found to be relevant in the pathogenesis of keratoconus. We sought to determine the influence of eye rubbing on protease expression, protease activity and concentration of inflammatory molecules in tears. Basal tears were collected from normal volunteers before and after 60 seconds of experimental eye rubbing. The total amount of matrix metalloproteinase (MMP)-13 and inflammatory molecules interleukin (IL)-6 and tumour necrosis factor (TNF)-α in the tear samples were measured using specific enzyme-linked immunosorbent assays (ELISA). Tear collagenase activity was investigated using a specific activity assay. The concentrations of MMP-13 (51.9 ± 34.3 versus 63 ± 36.8 pg/ml, p = 0.006), IL-6 (1.24 ± 0.98 versus 2.02 ± 1.52 pg/ml, p = 0.004) and TNF-α (1.16 ± 0.74 versus 1.44 ± 0.66 pg/ml, p = 0.003) were significantly increased in normal subjects after eye rubbing. The experimental eye rub did not alter significantly the collagenase activity (5.02 ± 3 versus 7.50 ± 3.90 fluorescent intensity units, p = 0.14) of tears. Eye rubbing for 60 seconds increased the level of tear MMP-13, IL-6 and TNF-α in normal study subjects. This increase in protease, protease activity and inflammatory mediators in tears after eye rubbing may be exacerbated even further during persistent and forceful eye rubbing seen in people with keratoconus and this in turn may contribute to the progression of the disease. © 2013 The Authors. Clinical and Experimental Optometry © 2013 Optometrists Association Australia.

Estimation of the mechanical properties of the eye through the study of its vibrational modes.

PubMed

Aloy, M Á; Adsuara, J E; Cerdá-Durán, P; Obergaulinger, M; Esteve-Taboada, J J; Ferrer-Blasco, T; Montés-Micó, R

2017-01-01

Measuring the eye's mechanical properties in vivo and with minimally invasive techniques can be the key for individualized solutions to a number of eye pathologies. The development of such techniques largely relies on a computational modelling of the eyeball and, it optimally requires the synergic interplay between experimentation and numerical simulation. In Astrophysics and Geophysics the remote measurement of structural properties of the systems of their realm is performed on the basis of (helio-)seismic techniques. As a biomechanical system, the eyeball possesses normal vibrational modes encompassing rich information about its structure and mechanical properties. However, the integral analysis of the eyeball vibrational modes has not been performed yet. Here we develop a new finite difference method to compute both the spheroidal and, specially, the toroidal eigenfrequencies of the human eye. Using this numerical model, we show that the vibrational eigenfrequencies of the human eye fall in the interval 100 Hz-10 MHz. We find that compressible vibrational modes may release a trace on high frequency changes of the intraocular pressure, while incompressible normal modes could be registered analyzing the scattering pattern that the motions of the vitreous humour leave on the retina. Existing contact lenses with embebed devices operating at high sampling frequency could be used to register the microfluctuations of the eyeball shape we obtain. We advance that an inverse problem to obtain the mechanical properties of a given eye (e.g., Young's modulus, Poisson ratio) measuring its normal frequencies is doable. These measurements can be done using non-invasive techniques, opening very interesting perspectives to estimate the mechanical properties of eyes in vivo. Future research might relate various ocular pathologies with anomalies in measured vibrational frequencies of the eye.

Scanning laser polarimetry in eyes with exfoliation syndrome.

PubMed

Dimopoulos, Antonios T; Katsanos, Andreas; Mikropoulos, Dimitrios G; Giannopoulos, Theodoros; Empeslidis, Theodoros; Teus, Miguel A; Holló, Gábor; Konstas, Anastasios G P

2013-01-01

To compare retinal nerve fiber layer thickness (RNFLT) of normotensive eyes with exfoliation syndrome (XFS) and healthy eyes.
 Sixty-four consecutive individuals with XFS and normal office-time intraocular pressure (IOP) and 72 consecutive healthy controls were prospectively enrolled for a cross-sectional analysis in this hospital-based observational study. The GDx-VCC parameters (temporal-superior-nasal-inferior-temporal [TSNIT] average, superior average, inferior average, TSNIT standard deviation (SD), and nerve fiber indicator [NFI]) were compared between groups. Correlation between various clinical parameters and RNFLT parameters was investigated with Spearman coefficient. 
 The NFI, although within normal limits for both groups, was significantly greater in the XFS group compared to controls: the respective median and interquartile range (IQR) values were 25.1 (22.0-29.0) vs 15.0 (12.0-20.0), p<0.001. In the XFS group, all RNFLT values were significantly lower compared to controls (p<0.001). However, they were all within the normal clinical ranges for both groups: TSNIT average median (IQR): 52.8 (49.7-55.7) vs 56.0 (53.0-59.3) µm; superior average mean (SD): 62.3 (6.7) vs 68.8 (8.2) µm; inferior average mean (SD): 58.0 (7.2) vs 64.8 (7.7) µm, respectively. TSNIT SD was significantly lower in the XFS group, median (IQR): 18.1 (15.4-20.4) vs 21.0 (18.4-23.8), p<0.001. There was no systematic relationship between RNFLT and visual acuity, cup-to-disc ratio, IOP, central corneal thickness, Humphrey mean deviation, and pattern standard deviation in either group. 
 Compared to control eyes, polarimetry-determined RNFLT was lower in XFS eyes with normal IOP. Therefore, close monitoring of RNFLT may facilitate early identification of those XFS eyes that convert to exfoliative glaucoma.

Gross, histologic, and computed tomographic characterization of nonpathological intrascleral cartilage and bone in the domestic goat (Capra aegagrus hircus).

PubMed

Tusler, Charlotte A; Good, Kathryn L; Maggs, David J; Zwingenberger, Allison L; Reilly, Christopher M

2017-05-01

To characterize grossly, histologically, and via computed tomography (CT) the appearance of intrascleral cartilage, bone, or both in domestic goats with otherwise normal eyes and to correlate this with age, sex, and breed. Sixty-eight domestic goats (89 eyes). Forty-nine formalin-fixed globes from 38 goats underwent high-resolution CT, and gross and light microscopic examination. An additional 40 eyes from 30 goats underwent light microscopy only. Age, breed, and sex of affected goats were retrieved from medical records. Considering all methods of evaluation collectively, cartilage was detected in 42% of eyes (44% of goats) and bone in 11% of eyes (12% of goats); bone was never seen without cartilage. Goats in which bone, cartilage, or both were detected ranged from 0.25 to 13 (median = 3.5) years of age, represented 11 of 12 breeds of the study population, and had a male:female ratio of 11:19. Bone was detected in the eyes of significantly more males (n = 8) than females (n = 2). No sex predilection was noted for cartilage alone. Histology revealed intrascleral chondrocyte-like cells, hyaline cartilage, and islands of lamellar bone. Some regions of bone had central, adipose-rich, marrow-like cavities. CT localized mineralized tissue as adjacent to or partially surrounding the optic nerve head. This is the first report of intrascleral bone or cartilage in a normal goat and of intrascleral bone in an otherwise normal mammal. The high prevalence of intrascleral cartilage and bone in this study suggests that this finding is normal and likely represents an adaptation in goats. © 2016 American College of Veterinary Ophthalmologists.

Wave aberrations in rhesus monkeys with vision-induced ametropias

PubMed Central

Ramamirtham, Ramkumar; Kee, Chea-su; Hung, Li-Fang; Qiao-Grider, Ying; Huang, Juan; Roorda, Austin; Smith, Earl L.

2007-01-01

The purpose of this study was to investigate the relationship between refractive errors and high-order aberrations in infant rhesus monkeys. Specifically, we compared the monochromatic wave aberrations measured with a Shack-Hartman wavefront sensor between normal monkeys and monkeys with vision-induced refractive errors. Shortly after birth, both normal monkeys and treated monkeys reared with optically induced defocus or form deprivation showed a decrease in the magnitude of high-order aberrations with age. However, the decrease in aberrations was typically smaller in the treated animals. Thus, at the end of the lens-rearing period, higher than normal amounts of aberrations were observed in treated eyes, both hyperopic and myopic eyes and treated eyes that developed astigmatism, but not spherical ametropias. The total RMS wavefront error increased with the degree of spherical refractive error, but was not correlated with the degree of astigmatism. Both myopic and hyperopic treated eyes showed elevated amounts of coma and trefoil and the degree of trefoil increased with the degree of spherical ametropia. Myopic eyes also exhibited a much higher prevalence of positive spherical aberration than normal or treated hyperopic eyes. Following the onset of unrestricted vision, the amount of high-order aberrations decreased in the treated monkeys that also recovered from the experimentally induced refractive errors. Our results demonstrate that high-order aberrations are influenced by visual experience in young primates and that the increase in high-order aberrations in our treated monkeys appears to be an optical byproduct of the vision-induced alterations in ocular growth that underlie changes in refractive error. The results from our study suggest that the higher amounts of wave aberrations observed in ametropic humans are likely to be a consequence, rather than a cause, of abnormal refractive development. PMID:17825347

Microarray analysis on gene regulation by estrogen, progesterone and tamoxifen in human endometrial stromal cells.

PubMed

Ren, Chun-E; Zhu, Xueqiong; Li, Jinping; Lyle, Christian; Dowdy, Sean; Podratz, Karl C; Byck, David; Chen, Hai-Bin; Jiang, Shi-Wen

2015-03-13

Epithelial stromal cells represent a major cellular component of human uterine endometrium that is subject to tight hormonal regulation. Through cell-cell contacts and/or paracrine mechanisms, stromal cells play a significant role in the malignant transformation of epithelial cells. We isolated stromal cells from normal human endometrium and investigated the morphological and transcriptional changes induced by estrogen, progesterone and tamoxifen. We demonstrated that stromal cells express appreciable levels of estrogen and progesterone receptors and undergo different morphological changes upon hormonal stimulation. Microarray analysis indicated that both estrogen and progesterone induced dramatic alterations in a variety of genes associated with cell structure, transcription, cell cycle, and signaling. However, divergent patterns of changes, and in some genes opposite effects, were observed for the two hormones. A large number of genes are identified as novel targets for hormonal regulation. These hormone-responsive genes may be involved in normal uterine function and the development of endometrial malignancies.

Regulation of gene expression in the mammalian eye and its relevance to eye disease

PubMed Central

Scheetz, Todd E.; Kim, Kwang-Youn A.; Swiderski, Ruth E.; Philp, Alisdair R.; Braun, Terry A.; Knudtson, Kevin L.; Dorrance, Anne M.; DiBona, Gerald F.; Huang, Jian; Casavant, Thomas L.; Sheffield, Val C.; Stone, Edwin M.

2006-01-01

We used expression quantitative trait locus mapping in the laboratory rat (Rattus norvegicus) to gain a broad perspective of gene regulation in the mammalian eye and to identify genetic variation relevant to human eye disease. Of >31,000 gene probes represented on an Affymetrix expression microarray, 18,976 exhibited sufficient signal for reliable analysis and at least 2-fold variation in expression among 120 F2 rats generated from an SR/JrHsd × SHRSP intercross. Genome-wide linkage analysis with 399 genetic markers revealed significant linkage with at least one marker for 1,300 probes (α = 0.001; estimated empirical false discovery rate = 2%). Both contiguous and noncontiguous loci were found to be important in regulating mammalian eye gene expression. We investigated one locus of each type in greater detail and identified putative transcription-altering variations in both cases. We found an inserted cREL binding sequence in the 5′ flanking sequence of the Abca4 gene associated with an increased expression level of that gene, and we found a mutation of the gene encoding thyroid hormone receptor β2 associated with a decreased expression level of the gene encoding short-wavelength sensitive opsin (Opn1sw). In addition to these positional studies, we performed a pairwise analysis of gene expression to identify genes that are regulated in a coordinated manner and used this approach to validate two previously undescribed genes involved in the human disease Bardet–Biedl syndrome. These data and analytical approaches can be used to facilitate the discovery of additional genes and regulatory elements involved in human eye disease. PMID:16983098

Sarcoidosis

MedlinePlus

... larger than normal spleen Anemia Burning, itchy, or dry eyes Fainting Heart palpitations Joint pain Muscle weakness Problems ... problems with the nervous system; burning, itching, or dry eyes; swollen salivary glands; swollen lymph nodes in the ...

Tumor formation of prostate cancer cells influenced by stromal cells from the transitional or peripheral zones of the normal prostate

PubMed Central

Zhao, Fu-Jun; Han, Bang-Min; Yu, Sheng-Qiang; Xia, Shu-Jie

2009-01-01

This study was designed to investigate the different involvements of prostatic stromal cells from the normal transitional zone (TZ) or peripheral zone (PZ) in the carcinogenesis of prostate cancer (PCa) epithelial cells (PC-3) in vitro and in vivo co-culture models. Ultra-structures and gene expression profiles of primary cultures of human prostatic stromal cells from the normal TZ or PZ were analyzed by electron microscopy and microarray analysis. In vitro and in vivo co-culture models composed of normal TZ or PZ stromal cells and human PCa PC-3 cells were established. We assessed tumor growth and weight in the in vivo nude mice model. There are morphological and ultra-structural differences in stromal cells from TZ and PZ of the normal prostate. In all, 514 differentially expressed genes were selected by microarray analysis; 483 genes were more highly expressed in stromal cells from TZ and 31 were more highly expressed in those from PZ. Co-culture with PZ stromal cells and transforming growth factor-β1 (TGF-β1) increased the tumor growth of PC-3 cells in vitro and in vivo, as well as Bcl-2 expression. On the other hand, stromal cells of TZ suppressed PC-3 cell tumor growth in the mouse model. We conclude that ultra-structures and gene expression differ between the stromal cells from TZ or PZ of the normal prostate, and stroma–epithelium interactions from TZ or PZ might be responsible for the distinct zonal localization of prostate tumor formation. PMID:19122679

Diagnosing dry eye with dynamic-area high-speed videokeratoscopy

NASA Astrophysics Data System (ADS)

Alonso-Caneiro, David; Turuwhenua, Jason; Iskander, D. Robert; Collins, Michael J.

2011-07-01

Dry eye syndrome is one of the most commonly reported eye health conditions. Dynamic-area high-speed videokeratoscopy (DA-HSV) represents a promising alternative to the most invasive clinical methods for the assessment of the tear film surface quality (TFSQ), particularly as Placido-disk videokeratoscopy is both relatively inexpensive and widely used for corneal topography assessment. Hence, improving this technique to diagnose dry eye is of clinical significance and the aim of this work. First, a novel ray-tracing model is proposed that simulates the formation of a Placido image. This model shows the relationship between tear film topography changes and the obtained Placido image and serves as a benchmark for the assessment of indicators of the ring's regularity. Further, a novel block-feature TFSQ indicator is proposed for detecting dry eye from a series of DA-HSV measurements. The results of the new indicator evaluated on data from a retrospective clinical study, which contains 22 normal and 12 dry eyes, have shown a substantial improvement of the proposed technique to discriminate dry eye from normal tear film subjects. The best discrimination was obtained under suppressed blinking conditions. In conclusion, this work highlights the potential of the DA-HSV as a clinical tool to diagnose dry eye syndrome.

A Microwell-Printing Fabrication Strategy for the On-Chip Templated Biosynthesis of Protein Microarrays for Surface Plasmon Resonance Imaging

PubMed Central

Manuel, Gerald; Lupták, Andrej; Corn, Robert M.

2017-01-01

A two-step templated, ribosomal biosynthesis/printing method for the fabrication of protein microarrays for surface plasmon resonance imaging (SPRI) measurements is demonstrated. In the first step, a sixteen component microarray of proteins is created in microwells by cell free on chip protein synthesis; each microwell contains both an in vitro transcription and translation (IVTT) solution and 350 femtomoles of a specific DNA template sequence that together are used to create approximately 40 picomoles of a specific hexahistidine-tagged protein. In the second step, the protein microwell array is used to contact print one or more protein microarrays onto nitrilotriacetic acid (NTA)-functionalized gold thin film SPRI chips for real-time SPRI surface bioaffinity adsorption measurements. Even though each microwell array element only contains approximately 40 picomoles of protein, the concentration is sufficiently high for the efficient bioaffinity adsorption and capture of the approximately 100 femtomoles of hexahistidine-tagged protein required to create each SPRI microarray element. As a first example, the protein biosynthesis process is verified with fluorescence imaging measurements of a microwell array containing His-tagged green fluorescent protein (GFP), yellow fluorescent protein (YFP) and mCherry (RFP), and then the fidelity of SPRI chips printed from this protein microwell array is ascertained by measuring the real-time adsorption of various antibodies specific to these three structurally related proteins. This greatly simplified two-step synthesis/printing fabrication methodology eliminates most of the handling, purification and processing steps normally required in the synthesis of multiple protein probes, and enables the rapid fabrication of SPRI protein microarrays from DNA templates for the study of protein-protein bioaffinity interactions. PMID:28706572

Equalizer reduces SNP bias in Affymetrix microarrays.

PubMed

Quigley, David

2015-07-30

Gene expression microarrays measure the levels of messenger ribonucleic acid (mRNA) in a sample using probe sequences that hybridize with transcribed regions. These probe sequences are designed using a reference genome for the relevant species. However, most model organisms and all humans have genomes that deviate from their reference. These variations, which include single nucleotide polymorphisms, insertions of additional nucleotides, and nucleotide deletions, can affect the microarray's performance. Genetic experiments comparing individuals bearing different population-associated single nucleotide polymorphisms that intersect microarray probes are therefore subject to systemic bias, as the reduction in binding efficiency due to a technical artifact is confounded with genetic differences between parental strains. This problem has been recognized for some time, and earlier methods of compensation have attempted to identify probes affected by genome variants using statistical models. These methods may require replicate microarray measurement of gene expression in the relevant tissue in inbred parental samples, which are not always available in model organisms and are never available in humans. By using sequence information for the genomes of organisms under investigation, potentially problematic probes can now be identified a priori. However, there is no published software tool that makes it easy to eliminate these probes from an annotation. I present equalizer, a software package that uses genome variant data to modify annotation files for the commonly used Affymetrix IVT and Gene/Exon platforms. These files can be used by any microarray normalization method for subsequent analysis. I demonstrate how use of equalizer on experiments mapping germline influence on gene expression in a genetic cross between two divergent mouse species and in human samples significantly reduces probe hybridization-induced bias, reducing false positive and false negative findings. The equalizer package reduces probe hybridization bias from experiments performed on the Affymetrix microarray platform, allowing accurate assessment of germline influence on gene expression.

Unilateral pigmentary degeneration of the retina associated with heterochromia iridis.

PubMed

Grisanti, S; Diestelhorst, M; Lebek, J; Walter, P; Heimann, K

1998-12-01

For the past 5 years, a 56-year-old patient has been displaying monocular progressive pigmentary changes in the left eye. Heterochromy of the left eye has been known since childhood. The other eye is clinically and functionally normal. The patient was adopted and he has no children. Therefore, we have no family history. The patient was examined clinically and by means of electroretinography, electrooculography, perimetry, computer tomography, pulsatile ocular blood flow (POBF) measurement, serology and Doppler sonography. Electrophysiology displayed a considerable reduction of scotopic and photopic ERGs, a reduced dark-through, and a reduced light-rise in the left eye, whereas the fellow eye was normal. The visual field was limited to 5 deg around the fixation point, and a peripheral crescent-shaped arch encircled the temporal-inferior quadrant concomitant to the pigmentary changes. By computer tomography and Doppler sonography a vascular affection was excluded. The left eye displayed lower POBF values. All serological tests were found negative. The clinical picture and negative exclusion criteria indicate a unilateral retinitis pigmentosa. However, with regard to the literature an unequivocal diagnosis can only be made upon hereditary evidence.

Bilateral phacoemulsification and intraocular lens implantation in a great horned owl.

PubMed

Carter, Renee T; Murphy, Christopher J; Stuhr, Charles M; Diehl, Kathryn A

2007-02-15

A great horned owl of estimated age < 1 year that was captured by wildlife rehabilitators was evaluated because of suspected cataracts. Nuclear and incomplete cortical cataracts were evident in both eyes. Ocular ultrasonography revealed no evidence of retinal detachment, and electroretinography revealed normal retinal function. For visual rehabilitation, cataract surgery was planned and intraocular lens design was determined on the basis of values obtained from the schematic eye, which is a mathematical model representing a normal eye for a species. Cataract surgery and intraocular lens placement were performed in both eyes. After surgery, refraction was within -0.75 diopters in the right eye and -0.25 diopters in the left eye. Visual rehabilitation was evident on the basis of improved tracking and feeding behavior, and the owl was eventually released into the wild. In raptors with substantial visual compromise, euthanasia or placement in a teaching facility is a typical outcome because release of such a bird is unacceptable. Successful intraocular lens implantation for visual rehabilitation and successful release into the wild are achievable.

In vivo optical imaging of amblyopia: Digital subtraction autofluorescence and split-spectrum amplitude-decorrelation angiography.

PubMed

Guo, Lei; Tao, Jun; Xia, Fan; Yang, Zhi; Ma, Xiaoli; Hua, Rui

2016-09-01

Amblyopia is a visual impairment that is attributed to either abnormal binocular interactions or visual deprivation. The retina and choroids have been shown to be involved in the development of amblyopia. The purpose of this study was to investigate the retinal and choroidal microstructural abnormalities of amblyopia using digital subtraction autofluorescence and split-spectrum amplitude-decorrelation angiography (SSADA) approaches. This prospective study included 44 eyes of 22 patients with unilateral amblyopia. All patients who received indirect ophthalmoscopy, combined depth imaging spectral domain optical coherence tomography (OCT), SSADA-OCT, and macular blue light (BL-) and near-infrared (NIR-) autofluorescences underwent pupil dilation. The subfoveal choroidal thickness (SFCT) was measured. BL- and NIR-autofluorescences were determined for all patients and used to generate subtraction images with ImageJ software. The superficial, deep layers of the retina, and inner choroid layer were required for SSADA-OCT. For the normal eyes, a regularly increasing signal was observed in the central macula based on the subtraction images. In contrast, a decreased signal for the central patch or a reduced peak was detected in 16 of 22 amblyopic eyes (72.7%). The mean SFCT of the amblyopic eyes was greater than that of the fellow normal eyes (399.25 ± 4.944 µm vs. 280.58 ± 6.491 µm, respectively, P < 0.05). SSADA-OCT revealed a normal choroidal capillary network in all fellow normal eyes. However, 18 of 22 amblyopic eyes (86.4%) exhibited a blurry choroidal capillary network, and 15 of 22 amblyopic eyes (68.2%) displayed a dark atrophic patch. This is the first report of amblyopia using SSADA-OCT and digital subtraction images of autofluorescence. The mechanistic relationship of a thicker choroid and choroidal capillary atrophy with amblyopia remains to be described. The digital subtraction image confirmed the changes in the microstructure of the amblyopic retina as a supplementary approach to detect the progression of amblyopia. Lasers Surg. Med. 48:660-667, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Detection of third and sixth cranial nerve palsies with a novel method for eye tracking while watching a short film clip

PubMed Central

Samadani, Uzma; Farooq, Sameer; Ritlop, Robert; Warren, Floyd; Reyes, Marleen; Lamm, Elizabeth; Alex, Anastasia; Nehrbass, Elena; Kolecki, Radek; Jureller, Michael; Schneider, Julia; Chen, Agnes; Shi, Chen; Mendhiratta, Neil; Huang, Jason H.; Qian, Meng; Kwak, Roy; Mikheev, Artem; Rusinek, Henry; George, Ajax; Fergus, Robert; Kondziolka, Douglas; Huang, Paul P.; Smith, R. Theodore

2015-01-01

OBJECT Automated eye movement tracking may provide clues to nervous system function at many levels. Spatial calibration of the eye tracking device requires the subject to have relatively intact ocular motility that implies function of cranial nerves (CNs) III (oculomotor), IV (trochlear), and VI (abducent) and their associated nuclei, along with the multiple regions of the brain imparting cognition and volition. The authors have developed a technique for eye tracking that uses temporal rather than spatial calibration, enabling detection of impaired ability to move the pupil relative to normal (neurologically healthy) control volunteers. This work was performed to demonstrate that this technique may detect CN palsies related to brain compression and to provide insight into how the technique may be of value for evaluating neuropathological conditions associated with CN palsy, such as hydrocephalus or acute mass effect. METHODS The authors recorded subjects’ eye movements by using an Eyelink 1000 eye tracker sampling at 500 Hz over 200 seconds while the subject viewed a music video playing inside an aperture on a computer monitor. The aperture moved in a rectangular pattern over a fixed time period. This technique was used to assess ocular motility in 157 neurologically healthy control subjects and 12 patients with either clinical CN III or VI palsy confirmed by neuro-ophthalmological examination, or surgically treatable pathological conditions potentially impacting these nerves. The authors compared the ratio of vertical to horizontal eye movement (height/width defined as aspect ratio) in normal and test subjects. RESULTS In 157 normal controls, the aspect ratio (height/width) for the left eye had a mean value ± SD of 1.0117 ± 0.0706. For the right eye, the aspect ratio had a mean of 1.0077 ± 0.0679 in these 157 subjects. There was no difference between sexes or ages. A patient with known CN VI palsy had a significantly increased aspect ratio (1.39), whereas 2 patients with known CN III palsy had significantly decreased ratios of 0.19 and 0.06, respectively. Three patients with surgically treatable pathological conditions impacting CN VI, such as infratentorial mass effect or hydrocephalus, had significantly increased ratios (1.84, 1.44, and 1.34, respectively) relative to normal controls, and 6 patients with supratentorial mass effect had significantly decreased ratios (0.27, 0.53, 0.62, 0.45, 0.49, and 0.41, respectively). These alterations in eye tracking all reverted to normal ranges after surgical treatment of underlying pathological conditions in these 9 neurosurgical cases. CONCLUSIONS This proof of concept series of cases suggests that the use of eye tracking to detect CN palsy while the patient watches television or its equivalent represents a new capacity for this technology. It may provide a new tool for the assessment of multiple CNS functions that can potentially be useful in the assessment of awake patients with elevated intracranial pressure from hydrocephalus or trauma. PMID:25495739

Detection of third and sixth cranial nerve palsies with a novel method for eye tracking while watching a short film clip.

PubMed

Samadani, Uzma; Farooq, Sameer; Ritlop, Robert; Warren, Floyd; Reyes, Marleen; Lamm, Elizabeth; Alex, Anastasia; Nehrbass, Elena; Kolecki, Radek; Jureller, Michael; Schneider, Julia; Chen, Agnes; Shi, Chen; Mendhiratta, Neil; Huang, Jason H; Qian, Meng; Kwak, Roy; Mikheev, Artem; Rusinek, Henry; George, Ajax; Fergus, Robert; Kondziolka, Douglas; Huang, Paul P; Smith, R Theodore

2015-03-01

Automated eye movement tracking may provide clues to nervous system function at many levels. Spatial calibration of the eye tracking device requires the subject to have relatively intact ocular motility that implies function of cranial nerves (CNs) III (oculomotor), IV (trochlear), and VI (abducent) and their associated nuclei, along with the multiple regions of the brain imparting cognition and volition. The authors have developed a technique for eye tracking that uses temporal rather than spatial calibration, enabling detection of impaired ability to move the pupil relative to normal (neurologically healthy) control volunteers. This work was performed to demonstrate that this technique may detect CN palsies related to brain compression and to provide insight into how the technique may be of value for evaluating neuropathological conditions associated with CN palsy, such as hydrocephalus or acute mass effect. The authors recorded subjects' eye movements by using an Eyelink 1000 eye tracker sampling at 500 Hz over 200 seconds while the subject viewed a music video playing inside an aperture on a computer monitor. The aperture moved in a rectangular pattern over a fixed time period. This technique was used to assess ocular motility in 157 neurologically healthy control subjects and 12 patients with either clinical CN III or VI palsy confirmed by neuro-ophthalmological examination, or surgically treatable pathological conditions potentially impacting these nerves. The authors compared the ratio of vertical to horizontal eye movement (height/width defined as aspect ratio) in normal and test subjects. In 157 normal controls, the aspect ratio (height/width) for the left eye had a mean value ± SD of 1.0117 ± 0.0706. For the right eye, the aspect ratio had a mean of 1.0077 ± 0.0679 in these 157 subjects. There was no difference between sexes or ages. A patient with known CN VI palsy had a significantly increased aspect ratio (1.39), whereas 2 patients with known CN III palsy had significantly decreased ratios of 0.19 and 0.06, respectively. Three patients with surgically treatable pathological conditions impacting CN VI, such as infratentorial mass effect or hydrocephalus, had significantly increased ratios (1.84, 1.44, and 1.34, respectively) relative to normal controls, and 6 patients with supratentorial mass effect had significantly decreased ratios (0.27, 0.53, 0.62, 0.45, 0.49, and 0.41, respectively). These alterations in eye tracking all reverted to normal ranges after surgical treatment of underlying pathological conditions in these 9 neurosurgical cases. This proof of concept series of cases suggests that the use of eye tracking to detect CN palsy while the patient watches television or its equivalent represents a new capacity for this technology. It may provide a new tool for the assessment of multiple CNS functions that can potentially be useful in the assessment of awake patients with elevated intracranial pressure from hydrocephalus or trauma.

Syringomyelia presenting with unilateral optic neuropathy: a case report.

PubMed

Ngoo, Qi Zhe; Tai, Evelyn Li Min; Wan Hitam, Wan Hazabbah

2017-01-01

In this case report, we present two cases of syringomyelia with optic neuropathy. In Case 1, a 36-year-old Malay lady presented to our clinic with acute onset of blurring of vision in her left eye that she experienced since past 1 month. She was diagnosed with syringomyelia 12 years ago and was on conservative management. Her visual acuity was 6/6 in the right eye and counting fingers at 1 m in the left. There was a positive relative afferent pupillary defect in her left eye. Optic nerve functions of her left eye were reduced. Visual field showed a left inferior field defect. Her extraocular muscle movements were full. Magnetic resonance imaging of the brain and spine showed syringomyelia at the level of C2-C6 and T2-T9. Both of her optic nerves were normal. Her condition improved with intravenous and oral corticosteroids. In Case 2, a 44-year-old Malay lady presented to our clinic with a progressive central scotoma in her right eye that she experienced since past 1 month. She had previous history of recurrent episodes of weakness in both of her lower limbs from past 8 months. Visual acuity in her right and left eye was 6/9 and 6/6, respectively. The relative afferent pupillary defect in her right eye was positive. Optic nerve functions of her right eye were affected. Visual field showed a central scotoma in her right eye. Her extraocular muscle movements were full. Fundoscopy of her right eye showed a pale optic disc. Her left eye fundus was normal. Magnetic resonance imaging of the brain and spine showed syringomyelia at T3-T6. Both of her optic nerves were normal. A diagnosis of syringomyelia with right optic atrophy was performed. Her condition improved with intravenous and oral corticosteroids. Optic neuropathy is a rare neuro-ophthalmic manifestation in patients with syringomyelia. Prompt diagnosis and timely management are essential to avoid a poor visual outcome. Intravenous corticosteroids are beneficial in the treatment of early optic neuropathy in syringomyelia.

Acute Zonal Cone Photoreceptor Outer Segment Loss.

PubMed

Aleman, Tomas S; Sandhu, Harpal S; Serrano, Leona W; Traband, Anastasia; Lau, Marisa K; Adamus, Grazyna; Avery, Robert A

2017-05-01

The diagnostic path presented narrows down the cause of acute vision loss to the cone photoreceptor outer segment and will refocus the search for the cause of similar currently idiopathic conditions. To describe the structural and functional associations found in a patient with acute zonal occult photoreceptor loss. A case report of an adolescent boy with acute visual field loss despite a normal fundus examination performed at a university teaching hospital. Results of a complete ophthalmic examination, full-field flash electroretinography (ERG) and multifocal ERG, light-adapted achromatic and 2-color dark-adapted perimetry, and microperimetry. Imaging was performed with spectral-domain optical coherence tomography (SD-OCT), near-infrared (NIR) and short-wavelength (SW) fundus autofluorescence (FAF), and NIR reflectance (REF). The patient was evaluated within a week of the onset of a scotoma in the nasal field of his left eye. Visual acuity was 20/20 OU, and color vision was normal in both eyes. Results of the fundus examination and of SW-FAF and NIR-FAF imaging were normal in both eyes, whereas NIR-REF imaging showed a region of hyporeflectance temporal to the fovea that corresponded with a dense relative scotoma noted on light-adapted static perimetry in the left eye. Loss in the photoreceptor outer segment detected by SD-OCT co-localized with an area of dense cone dysfunction detected on light-adapted perimetry and multifocal ERG but with near-normal rod-mediated vision according to results of 2-color dark-adapted perimetry. Full-field flash ERG findings were normal in both eyes. The outer nuclear layer and inner retinal thicknesses were normal. Localized, isolated cone dysfunction may represent the earliest photoreceptor abnormality or a distinct entity within the acute zonal occult outer retinopathy complex. Acute zonal occult outer retinopathy should be considered in patients with acute vision loss and abnormalities on NIR-REF imaging, especially if multimodal imaging supports an intact retinal pigment epithelium and inner retina but an abnormal photoreceptor outer segment.

High-resolution chromosomal microarrays in prenatal diagnosis significantly increase diagnostic power.

PubMed

Oneda, Beatrice; Baldinger, Rosa; Reissmann, Regina; Reshetnikova, Irina; Krejci, Pavel; Masood, Rahim; Ochsenbein-Kölble, Nicole; Bartholdi, Deborah; Steindl, Katharina; Morotti, Denise; Faranda, Marzia; Baumer, Alessandra; Asadollahi, Reza; Joset, Pascal; Niedrist, Dunja; Breymann, Christian; Hebisch, Gundula; Hüsler, Margaret; Mueller, René; Prentl, Elke; Wisser, Josef; Zimmermann, Roland; Rauch, Anita

2014-06-01

The objective of this study was to determine for the first time the reliability and the diagnostic power of high-resolution microarray testing in routine prenatal diagnostics. We applied high-resolution chromosomal microarray testing in 464 cytogenetically normal prenatal samples with any indication for invasive testing. High-resolution testing revealed a diagnostic yield of 6.9% and 1.6% in cases of fetal ultrasound anomalies and cases of advanced maternal age (AMA), respectively, which is similar to previous studies using low-resolution microarrays. In three (0.6%) additional cases with an indication of AMA, an aberration in susceptibility risk loci was detected. Moreover, one case (0.2%) showed an X-linked aberration in a female fetus, a finding relevant for future family planning. We found the rate of cases, in which the parents had to be tested for interpretation of unreported copy number variants (3.7%), and the rate of remaining variants of unknown significance (0.4%) acceptably low. Of note, these findings did not cause termination of pregnancy after expert genetic counseling. The 0.4% rate of confined placental mosaicism was similar to that observed by conventional karyotyping and notably involved a case of placental microdeletion. High-resolution prenatal microarray testing is a reliable technique that increases diagnostic yield by at least 17.3% when compared with conventional karyotyping, without an increase in the frequency of variants of uncertain significance. © 2014 John Wiley & Sons, Ltd.

Microarray analysis of genes associated with cell surface NIS protein levels in breast cancer.

PubMed

Beyer, Sasha J; Zhang, Xiaoli; Jimenez, Rafael E; Lee, Mei-Ling T; Richardson, Andrea L; Huang, Kun; Jhiang, Sissy M

2011-10-11

Na+/I- symporter (NIS)-mediated iodide uptake allows radioiodine therapy for thyroid cancer. NIS is also expressed in breast tumors, raising potential for radionuclide therapy of breast cancer. However, NIS expression in most breast cancers is low and may not be sufficient for radionuclide therapy. We aimed to identify biomarkers associated with NIS expression such that mechanisms underlying NIS modulation in human breast tumors may be elucidated. Published oligonucleotide microarray data within the National Center for Biotechnology Information Gene Expression Omnibus database were analyzed to identify gene expression tightly correlated with NIS mRNA level among human breast tumors. NIS immunostaining was performed in a tissue microarray composed of 28 human breast tumors which had corresponding oligonucleotide microarray data available for each tumor such that gene expression associated with cell surface NIS protein level could be identified. NIS mRNA levels do not vary among breast tumors or when compared to normal breast tissues when detected by Affymetrix oligonucleotide microarray platforms. Cell surface NIS protein levels are much more variable than their corresponding NIS mRNA levels. Despite a limited number of breast tumors examined, our analysis identified cysteinyl-tRNA synthetase as a biomarker that is highly associated with cell surface NIS protein levels in the ER-positive breast cancer subtype. Further investigation on genes associated with cell surface NIS protein levels within each breast cancer molecular subtype may lead to novel targets for selectively increasing NIS expression/function in a subset of breast cancers patients.

Integrated analysis of chromosome copy number variation and gene expression in cervical carcinoma

PubMed Central

Yan, Deng; Yi, Song; Chiu, Wang Chi; Qin, Liu Gui; Kin, Wong Hoi; Kwok Hung, Chung Tony; Linxiao, Han; Wai, Choy Kwong; Yi, Sui; Tao, Yang; Tao, Tang

2017-01-01

Objective This study was conducted to explore chromosomal copy number variations (CNV) and transcript expression and to examine pathways in cervical pathogenesis using genome-wide high resolution microarrays. Methods Genome-wide chromosomal CNVs were investigated in 6 cervical cancer cell lines by Human Genome CGH Microarray Kit (4x44K). Gene expression profiles in cervical cancer cell lines, primary cervical carcinoma and normal cervical epithelium tissues were also studied using the Whole Human Genome Microarray Kit (4x44K). Results Fifty common chromosomal CNVs were identified in the cervical cancer cell lines. Correlation analysis revealed that gene up-regulation or down-regulation is significantly correlated with genomic amplification (P=0.009) or deletion (P=0.006) events. Expression profiles were identified through cluster analysis. Gene annotation analysis pinpointed cell cycle pathways was significantly (P=1.15E-08) affected in cervical cancer. Common CNVs were associated with cervical cancer. Conclusion Chromosomal CNVs may contribute to their transcript expression in cervical cancer. PMID:29312578

Customizing chemotherapy for colon cancer: the potential of gene expression profiling.

PubMed

Mariadason, John M; Arango, Diego; Augenlicht, Leonard H

2004-06-01

The value of gene expression profiling, or microarray analysis, for the classification and prognosis of multiple forms of cancer is now clearly established. For colon cancer, expression profiling can readily discriminate between normal and tumor tissue, and to some extent between tumors of different histopathological stage and prognosis. While a definitive in vivo study demonstrating the potential of this methodology for predicting response to chemotherapy is presently lacking, the ability of microarrays to distinguish other subtleties of colon cancer phenotype, as well as recent in vitro proof-of-principle experiments utilizing colon cancer cell lines, illustrate the potential of this methodology for predicting the probability of response to specific chemotherapeutic agents. This review discusses some of the recent advances in the use of microarray analysis for understanding and distinguishing colon cancer subtypes, and attempts to identify challenges that need to be overcome in order to achieve the goal of using gene expression profiling for customizing chemotherapy in colon cancer.

Carbohydrate Microarrays Identify Blood Group Precursor Cryptic Epitopes as Potential Immunological Targets of Breast Cancer

PubMed Central

Wang, Denong; Tang, Jin; Liu, Shaoyi

2015-01-01

Using carbohydrate microarrays, we explored potential natural ligands of antitumor monoclonal antibody HAE3. This antibody was raised against a murine mammary tumor antigen but was found to cross-react with a number of human epithelial tumors in tissues. Our carbohydrate microarray analysis reveals that HAE3 is specific for an O-glycan cryptic epitope that is normally hidden in the cores of blood group substances. Using HAE3 to screen tumor cell surface markers by flow cytometry, we found that the HAE3 glycoepitope, gpHAE3, was highly expressed by a number of human breast cancer cell lines, including some triple-negative cancers that lack the estrogen, progesterone, and Her2/neu receptors. Taken together, we demonstrate that HAE3 recognizes a conserved cryptic glycoepitope of blood group precursors, which is nevertheless selectively expressed and surface-exposed in certain breast tumor cells. The potential of this class of O-glycan cryptic antigens in breast cancer subtyping and targeted immunotherapy warrants further investigation. PMID:26539555

Evaluation of two outlier-detection-based methods for detecting tissue-selective genes from microarray data.

PubMed

Kadota, Koji; Konishi, Tomokazu; Shimizu, Kentaro

2007-05-01

Large-scale expression profiling using DNA microarrays enables identification of tissue-selective genes for which expression is considerably higher and/or lower in some tissues than in others. Among numerous possible methods, only two outlier-detection-based methods (an AIC-based method and Sprent's non-parametric method) can treat equally various types of selective patterns, but they produce substantially different results. We investigated the performance of these two methods for different parameter settings and for a reduced number of samples. We focused on their ability to detect selective expression patterns robustly. We applied them to public microarray data collected from 36 normal human tissue samples and analyzed the effects of both changing the parameter settings and reducing the number of samples. The AIC-based method was more robust in both cases. The findings confirm that the use of the AIC-based method in the recently proposed ROKU method for detecting tissue-selective expression patterns is correct and that Sprent's method is not suitable for ROKU.

Integrated analysis of chromosome copy number variation and gene expression in cervical carcinoma.

PubMed

Yan, Deng; Yi, Song; Chiu, Wang Chi; Qin, Liu Gui; Kin, Wong Hoi; Kwok Hung, Chung Tony; Linxiao, Han; Wai, Choy Kwong; Yi, Sui; Tao, Yang; Tao, Tang

2017-12-12

This study was conducted to explore chromosomal copy number variations (CNV) and transcript expression and to examine pathways in cervical pathogenesis using genome-wide high resolution microarrays. Genome-wide chromosomal CNVs were investigated in 6 cervical cancer cell lines by Human Genome CGH Microarray Kit (4x44K). Gene expression profiles in cervical cancer cell lines, primary cervical carcinoma and normal cervical epithelium tissues were also studied using the Whole Human Genome Microarray Kit (4x44K). Fifty common chromosomal CNVs were identified in the cervical cancer cell lines. Correlation analysis revealed that gene up-regulation or down-regulation is significantly correlated with genomic amplification ( P =0.009) or deletion ( P =0.006) events. Expression profiles were identified through cluster analysis. Gene annotation analysis pinpointed cell cycle pathways was significantly ( P =1.15E-08) affected in cervical cancer. Common CNVs were associated with cervical cancer. Chromosomal CNVs may contribute to their transcript expression in cervical cancer.

Computerized system for recognition of autism on the basis of gene expression microarray data.

PubMed

Latkowski, Tomasz; Osowski, Stanislaw

2015-01-01

The aim of this paper is to provide a means to recognize a case of autism using gene expression microarrays. The crucial task is to discover the most important genes which are strictly associated with autism. The paper presents an application of different methods of gene selection, to select the most representative input attributes for an ensemble of classifiers. The set of classifiers is responsible for distinguishing autism data from the reference class. Simultaneous application of a few gene selection methods enables analysis of the ill-conditioned gene expression matrix from different points of view. The results of selection combined with a genetic algorithm and SVM classifier have shown increased accuracy of autism recognition. Early recognition of autism is extremely important for treatment of children and increases the probability of their recovery and return to normal social communication. The results of this research can find practical application in early recognition of autism on the basis of gene expression microarray analysis. Copyright © 2014 Elsevier Ltd. All rights reserved.

The hyper-fluorescent transitional bands in ultra-late phase of indocyanine green angiography in chronic central serous chorioretinopathy.

PubMed

Hua, Rui; Yao, Kai; Xia, Fan; Li, Jun; Guo, Lei; Yang, Guoxing; Tao, Jun

2016-03-01

Chronic central serous chorioretinopathy (CSCR) is regarded as a type of severe diffuse retinal pigment epitheliopathy. There is an atrophic tract at level of retinal pigment epithelium (RPE) due to hyper-permeability of choroidal vessels, along with photoreceptor (PR) atrophy. Indocyanine green angiography (ICGA) is considered a gold standard for diagnosis. The purpose of this work is to investigate the hyper-fluorescent transitional bands (HFTB) between hypo-fluorescent and normal regions of the retina in the ultra-late phase of ICGA in CSCR. 26 chronic CSCR eyes and 12 relative normal eyes received spectral domain optical coherence tomography (SD-OCT), and ICGA at the 24th hour after indocyanine green (ICG) intravenous injection. In the ultra-late phase, images showed homogenous fluorescence in all normal eyes. On the contrary, geographical hypofluorescent lesions with atrophy of RPE was noted in 26 chronic CSCR eyes. Moreover, HFTB with intact RPE and disrupted PR was detected in 20 out of 26 chronic CSCR eyes (76.9%). The HFTB may indicate the early damage in chronic CSCR. Ultra-late ICGA can monitor not only metabolic status by endogenous melanin, but also membrane function in RPE by exogenous ICG molecule. © 2015 Wiley Periodicals, Inc.

The dependence of binocular contrast sensitivities on binocular single vision in normal and amblyopic human subjects

PubMed Central

Hood, A S; Morrison, J D

2002-01-01

We have measured monocular and binocular contrast sensitivities in response to medium to high spatial frequencies of vertical sinusoidal grating patterns in normal subjects, anisometropic amblyopes, strabismic amblyopes and non-amblyopic esotropes. On binocular viewing, contrast sensitivities were slightly but significantly increased in normal subjects, markedly increased in anisometropes and esotropes with anomalous binocular single vision (BSV) and significantly reduced in esotropes and exotropes without BSV. Application of a prismatic correction to the strabismic eye in order to achieve bifoveal stimulation resulted in a significant reduction in contrast sensitivity in esotropes with and without anomalous BSV, in exotropes and in non-amblyopic esotropes. Control experiments in normal subjects with monocular viewing showed that degradative effects of the prism occurred only with high prism powers and at high spatial frequencies, thus establishing that the reduced contrast sensitivities were the consequence of bifoveal stimulation rather than optical degradation. Displacement of the image of the grating pattern by 2 deg in normal subjects and anisometropes by a dichoptic method to simulate a small angle esotropia had no effect on the contrast sensitivities recorded through the companion eye. By contrast, esotropes showed similar reductions in contrast sensitivity to those obtained with the prism experiments, confirming a fundamental difference between subjects with normal and abnormal ocular alignments. The results have thus established a suppressive action of the fovea of the amblyopic eye acting on the companion, non-amblyopic eye and indicate that correction of ocular misalignments in adult esotropes may be disadvantageous to binocular visual performance. PMID:11956347

Deformation of the Early Glaucomatous Monkey Optic Nerve Head Connective Tissue after Acute IOP Elevation in 3-D Histomorphometric Reconstructions

PubMed Central

Yang, Hongli; Thompson, Hilary; Roberts, Michael D.; Sigal, Ian A.; Downs, J. Crawford

2011-01-01

Purpose. To retest the hypothesis that monkey ONH connective tissues become hypercompliant in early experimental glaucoma (EEG), by using 3-D histomorphometric reconstructions, and to expand the characterization of EEG connective tissue deformation to nine EEG eyes. Methods. Trephinated ONH and peripapillary sclera from both eyes of nine monkeys that were perfusion fixed, with one normal eye at IOP 10 mm Hg and the other EEG eye at 10 (n = 3), 30 (n = 3), or 45 (n = 3) mm Hg were serial sectioned, 3-D reconstructed, 3-D delineated, and quantified with 3-D reconstruction techniques developed in prior studies by the authors. Overall, and for each monkey, intereye differences (EEG eye minus normal eye) for each parameter were calculated and compared by ANOVA. Hypercompliance in the EEG 30 and 45 eyes was assessed by ANOVA, and deformations in all nine EEG eyes were separately compared by region without regard for fixation IOP. Results. Hypercompliant deformation was not significant in the overall ANOVA, but was suggested in a subset of EEG 30/45 eyes. EEG eye deformations included posterior laminar deformation, neural canal expansion, lamina cribrosa thickening, and posterior (outward) bowing of the peripapillary sclera. Maximum posterior laminar deformation and scleral canal expansion co-localized to either the inferior nasal or superior temporal quadrants in the eyes with the least deformation and involved both quadrants in the eyes achieving the greatest deformation. Conclusions. The data suggest that, in monkey EEG, ONH connective tissue hypercompliance may occur only in a subset of eyes and that early ONH connective tissue deformation is maximized in the superior temporal and/or inferior nasal quadrants. PMID:20702834

Tear dynamics in healthy and dry eyes.

PubMed

Cerretani, Colin F; Radke, C J

2014-06-01

Dry-eye disease, an increasingly prevalent ocular-surface disorder, significantly alters tear physiology. Understanding the basic physics of tear dynamics in healthy and dry eyes benefits both diagnosis and treatment of dry eye. We present a physiological-based model to describe tear dynamics during blinking. Tears are compartmentalized over the ocular surface; the blink cycle is divided into three repeating phases. Conservation laws quantify the tear volume and tear osmolarity of each compartment during each blink phase. Lacrimal-supply and tear-evaporation rates are varied to reveal the dependence of tear dynamics on dry-eye conditions, specifically tear osmolarity, tear volume, tear-turnover rate (TTR), and osmotic water flow. Predicted periodic-steady tear-meniscus osmolarity is 309 and 321 mOsM in normal and dry eyes, respectively. Tear osmolarity, volume, and TTR all match available clinical measurements. Osmotic water flow through the cornea and conjunctiva contribute 10 and 50% to the total tear supply in healthy and dry-eye conditions, respectively. TTR in aqueous-deficient dry eye (ADDE) is only half that in evaporative dry eye (EDE). The compartmental periodic-steady tear-dynamics model accurately predicts tear behavior in normal and dry eyes. Inclusion of osmotic water flow is crucial to match measured tear osmolarity. Tear-dynamics predictions corroborate the use of TTR as a clinical discriminator between ADDE and EDE. The proposed model is readily extended to predict the dynamics of aqueous solutes such as drugs or fluorescent tags.

Ocular abnormalities in mice lacking the immunoglobulin superfamily member Cdo.

PubMed

Zhang, Wei; Mulieri, Philip J; Gaio, Ursula; Bae, Gyu-Un; Krauss, Robert S; Kang, Jong-Sun

2009-10-01

Vertebrate eye development requires a series of complex morphogenetic and inductive events to produce a lens vesicle centered within the bilayered optic cup and a posteriorly positioned optic stalk. Multiple congenital eye defects, including microphthalmia and coloboma, result from defects in early eye morphogenesis. Cdo is a multifunctional cell surface immunoglobulin superfamily member that interacts with and mediates signaling by cadherins and netrins to regulate myogenesis. In addition, Cdo plays an essential role in early forebrain development by functioning as coreceptor for sonic hedgehog. It is reported here that Cdo is expressed in a dynamic, but dorsally restricted, fashion during early eye development, and that mice lacking Cdo display multiple eye defects. Anomalies seen in Cdo(-/-) mice include coloboma (failure to close the optic fissure); failure to form a proper boundary between the retinal pigmented epithelium and optic stalk; defective lens formation, including failure to separate from the surface ectoderm; and microphthalmia. Consistent with this wide array of defects, developing eyes of Cdo(-/-) mice show altered expression of several regulators of dorsoventral eye patterning, including Pax6, Pax2, and Tbx5. Taken together, these findings show that Cdo is required for normal eye development and is required for normal expression of patterning genes in both the ventral and dorsal domains. The multiple eye development defects seen in Cdo(-/-) mice suggest that mutations in human Cdo could contribute to congenital eye anomalies, such as Jacobsen syndrome, which is frequently associated with ocular defects, including coloboma and Peters' anomaly.

Development and validation of a gene expression oligo microarray for the gilthead sea bream (Sparus aurata).

PubMed

Ferraresso, Serena; Vitulo, Nicola; Mininni, Alba N; Romualdi, Chiara; Cardazzo, Barbara; Negrisolo, Enrico; Reinhardt, Richard; Canario, Adelino V M; Patarnello, Tomaso; Bargelloni, Luca

2008-12-03

Aquaculture represents the most sustainable alternative of seafood supply to substitute for the declining marine fisheries, but severe production bottlenecks remain to be solved. The application of genomic technologies offers much promise to rapidly increase our knowledge on biological processes in farmed species and overcome such bottlenecks. Here we present an integrated platform for mRNA expression profiling in the gilthead sea bream (Sparus aurata), a marine teleost of great importance for aquaculture. A public data base was constructed, consisting of 19,734 unique clusters (3,563 contigs and 16,171 singletons). Functional annotation was obtained for 8,021 clusters. Over 4,000 sequences were also associated with a GO entry. Two 60mer probes were designed for each gene and in-situ synthesized on glass slides using Agilent SurePrint technology. Platform reproducibility and accuracy were assessed on two early stages of sea bream development (one-day and four days old larvae). Correlation between technical replicates was always > 0.99, with strong positive correlation between paired probes. A two class SAM test identified 1,050 differentially expressed genes between the two developmental stages. Functional analysis suggested that down-regulated transcripts (407) in older larvae are mostly essential/housekeeping genes, whereas tissue-specific genes are up-regulated in parallel with the formation of key organs (eye, digestive system). Cross-validation of microarray data was carried out using quantitative qRT-PCR on 11 target genes, selected to reflect the whole range of fold-change and both up-regulated and down-regulated genes. A statistically significant positive correlation was obtained comparing expression levels for each target gene across all biological replicates. Good concordance between qRT-PCR and microarray data was observed between 2- and 7-fold change, while fold-change compression in the microarray was present for differences greater than 10-fold in the qRT-PCR. A highly reliable oligo-microarray platform was developed and validated for the gilthead sea bream despite the presently limited knowledge of the species transcriptome. Because of the flexible design this array will be able to accommodate additional probes as soon as novel unique transcripts are available.

Effects of strabismic amblyopia and strabismus without amblyopia on visuomotor behavior: III. Temporal eye-hand coordination during reaching.

PubMed

Niechwiej-Szwedo, Ewa; Goltz, Herbert C; Chandrakumar, Manokaraananthan; Wong, Agnes M F

2014-11-11

To examine the effects of strabismic amblyopia and strabismus only, without amblyopia, on the temporal patterns of eye-hand coordination during both the planning and execution stages of visually-guided reaching. Forty-six adults (16 with strabismic amblyopia, 14 with strabismus only, and 16 visually normal) executed reach-to-touch movements toward targets presented randomly 5° or 10° to the left or right of central fixation. Viewing conditions were binocular, monocular viewing with the amblyopic eye, and monocular viewing with the fellow eye (dominant and nondominant viewing for participants without amblyopia). Temporal coordination between eye and hand movements was examined during reach planning (interval between the initiation of saccade and reaching, i.e., saccade-to-reach planning interval) and reach execution (interval between the initiation of saccade and reach peak velocity [PV], i.e., saccade-to-reach PV interval). The frequency and dynamics of secondary reach-related saccades were also examined. The temporal patterns of eye-hand coordination prior to reach initiation were comparable among participants with strabismic amblyopia, strabismus only, and visually normal adults. However, the reach acceleration phase of participants with strabismic amblyopia and those with strabismus only were longer following target fixation (saccade-to-reach PV interval) than that of visually normal participants (P < 0.05). This effect was evident under all viewing conditions. The saccade-to-reach planning interval and the saccade-to-reach PV interval were not significantly different among participants with amblyopia with different levels of acuity and stereo acuity loss. Participants with strabismic amblyopia and strabismus only initiated secondary reach-related saccades significantly more frequently than visually normal participants. The amplitude and peak velocity of these saccades were significantly greater during amblyopic eye viewing in participants with amblyopia who also had negative stereopsis. Adults with strabismic amblyopia and strabismus only showed an altered pattern of temporal eye-hand coordination during the reach acceleration phase, which might affect their ability to modify reach trajectory using early online control. Secondary reach-related saccades may provide a compensatory mechanism with which to facilitate the late online control process in order to ensure relatively good reaching performance during binocular and fellow eye viewing. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

6-Hydroxy dopamine does not affect lens-induced refractive errors but suppresses deprivation myopia.

PubMed

Schaeffel, F; Hagel, G; Bartmann, M; Kohler, K; Zrenner, E

1994-01-01

Degradation of the retinal image by translucent occluders during postnatal development induces axial myopia in chickens, tree shrews and monkeys. Local visual deprivation produces myopia even in local regions of the eye and neither accommodation nor intact connection between the eye and the brain are necessary. Therefore, it is an important question whether a similar local-retinal pathway translating visual information into growth or stretch signals to the underlying sclera is acting to emmetropize the growing eye. It is not known until now whether occluder deprivation triggers similar eye growth (or scleral stretch) mechanisms that are also responsible for visual guidance of normal refractive development. We here report that, in chickens, 6-hydroxy dopamine suppresses deprivation-induced myopia but has no effect on the magnitude of changes in axial eye elongation that are induced by spectacle lenses. The result suggests that, in chickens with normal accommodation, two pharmacologically different feedback loops may be responsible for deprivation myopia and lens-induced refractive errors.

Acute shallowing of the anterior chamber.

PubMed Central

Mapstone, R

1981-01-01

In aging eyes phenylephrine drops have no significant effect on the depth of the anterior chamber, whereas pilocarpine drops produce a significant shallowing. If both drugs are instilled simultaneously, a significantly greater decrease in anterior chamber depth occurs. The effect is seen in normal, glaucomatous, and hypertensive eyes, and in eyes with shallow anterior chambers. It did not occur in eyes that had had an iridectomy. During the course of a positive provocative test an acute reduction in anterior depth occurs which is reversed when the angle opens and pressure returns to normal levels. It is concluded that the depth of the anterior chamber is not a static dimension but that changes can occur which are rapid and transient. The mechanism of shallowing and deepening depends on an increase or a decrease in the pupil block force. It is a necessary consequence too that eyes with nonshallow anterior chambers can get closed-angle glaucoma and that this possibility cannot be detected by a conventional gonioscopic approach. PMID:6455153

Albinism

MedlinePlus

... normal skin and hair Patches of missing skin color Many forms of albinism are associated with the following symptoms: Crossed eyes Light sensitivity Rapid eye movements Vision problems, or functional blindness Exams and Tests Genetic testing offers the most ...

Eye-Target Synchrony and Attention

NASA Astrophysics Data System (ADS)

Contreras, R.; Kolster, R.; Basu, S.; Voss, H. U.; Ghajar, J.; Suh, M.; Bahar, S.

2007-03-01

Eye-target synchrony is critical during smooth pursuit. We apply stochastic phase synchronization to human pursuit of a moving target, in both normal and mild traumatic brain injured (TBI) subjects. Smooth pursuit utilizes the same neural networks used by attention. To test whether smooth pursuit is modulated by attention, subjects tracked a target while loaded with tasks involving working memory. Preliminary results suggest that additional cognitive load increases normal subjects' performance, while the effect is reversed in TBI patients. We correlate these results with eye-target synchrony. Additionally, we correlate eye-target synchrony with frequency of target motion, and discuss how the range of frequencies for optimal synchrony depends on the shift from attentional to automatic-response time scales. Synchrony deficits in TBI patients can be correlated with specific regions of brain damage imaged with diffusion tensor imaging (DTI).

Altered characteristics of balance control in obese older adults.

PubMed

Melzer, Itshak; Oddsson, Lars I E

2016-01-01

Obesity is one of the most significant epidemiological trends of the last decades. Recently it was found that obese individuals show postural instability. Balance control mechanisms in obese older adults were less studied. Therefore we aimed to investigate the effect of obesity on balance control mechanisms in older adults. Parameters from Stabilogram-Diffusion Analysis (SDA) and measures from summary statistics of foot centre-of-pressure (COP) displacements along the anterior-posterior (AP) and mediolateral (ML) directions in eyes open and eyes closed conditions were used to characterize postural control in 22 obese (30-<35kg/m(2)), 26 overweight (25-<30kg/m(2)), and 18 normal weight subjects (18.5-<25kg/m(2)). Obese group subjects demonstrated significantly greater transition displacement, transition time interval, and short-term scaling exponent in the ML-direction compared with the normal weight group (eyes open and closed). In the AP-direction the obese group showed greater transition displacement (eyes open) and short-term scaling exponent (eyes open and closed). Average AP-COP and ML-COP ranges of COP sway were higher in the obese group compared with the normal weight group (eyes open and closed). This work indicates an altered postural control process in obese older adults. A greater sway displacement before closed-loop feedback mechanisms are called into play was seen in the ML direction that may lead to a higher risk of instability and fall events. Copyright © 2015 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.

Effect of ultrasound radiation force on the choroid.

PubMed

Silverman, Ronald H; Urs, Raksha; Lloyd, Harriet O

2013-01-10

While visualization of the retina and choroid has made great progress, functional imaging techniques have been lacking. Our aim was to utilize acoustic radiation force impulse (ARFI) response to probe functional properties of these tissues. A single element 18-MHz ultrasound transducer was focused upon the retina of the rabbit eye. The procedure was performed with the eye proptosed and with the eye seated normally in the orbit. The transducer was excited to emit ARFI over a 10-ms period with a 25% duty cycle. Phase resolved pulse/echo data were acquired before, during, and following ARFI. In the proptosed eye, ARFI exposure produced tissue displacements ranging from 0 to 10 μm, and an immediate increase in choroidal echo amplitude to over 6 dB, decaying to baseline after about 1 second. In the normally seated eye, ultrasound phase shifts consistent with flow were observed in the choroid, but enhanced backscatter following ARFI rarely occurred. ARFI-induced displacements of about 10 μm were observed at the choroidal margins. Larger displacements occurred within the choroid and in orbital tissues. We hypothesize that elevated intraocular pressure occurring during proptosis induced choroidal ischemia and that acoustic radiation force produced a transient local decompression and reperfusion. With the eye normally seated, choroidal flow was observed and little alteration in backscatter resulted from exposure. Clinical application of this technique may provide new insights into diseases characterized by altered choroidal hemodynamics, including maculopathies, diabetic retinopathy, and glaucoma.

PAX3 gene deletion detected by microarray analysis in a girl with hearing loss.

PubMed

Drozniewska, Malgorzata; Haus, Olga

2014-01-01

Deletions of the PAX3 gene have been rarely reported in the literature. Mutations of this gene are a common cause of Waardenburg syndrome type 1 and 3. We report a 16 year old female presenting hearing loss and normal intellectual development, without major features of Waardenburg syndrome type 1, and without family history of the syndrome. Her phenotype, however, overlaps with features of craniofacial-deafness-hand syndrome. Microarray analysis showed ~862 kb de novo deletion at 2q36.1 including PAX3. The above findings suggest that the rearrangement found in our patient appeared de novo and with high probability is a cause of her phenotype.

Eye Absence Does Not Regulate Planarian Stem Cells during Eye Regeneration.

PubMed

LoCascio, Samuel A; Lapan, Sylvain W; Reddien, Peter W

2017-02-27

Dividing cells called neoblasts contain pluripotent stem cells and drive planarian flatworm regeneration from diverse injuries. A long-standing question is whether neoblasts directly sense and respond to the identity of missing tissues during regeneration. We used the eye to investigate this question. Surprisingly, eye removal was neither sufficient nor necessary for neoblasts to increase eye progenitor production. Neoblasts normally increase eye progenitor production following decapitation, facilitating regeneration. Eye removal alone, however, did not induce this response. Eye regeneration following eye-specific resection resulted from homeostatic rates of eye progenitor production and less cell death in the regenerating eye. Conversely, large head injuries that left eyes intact increased eye progenitor production. Large injuries also non-specifically increased progenitor production for multiple uninjured tissues. We propose a model for eye regeneration in which eye tissue production by planarian stem cells is not directly regulated by the absence of the eye itself. Copyright © 2017 Elsevier Inc. All rights reserved.

An alternative method to amplify RNA without loss of signal conservation for expression analysis with a proteinase DNA microarray in the ArrayTube format.

PubMed

Schüler, Susann; Wenz, Ingrid; Wiederanders, B; Slickers, P; Ehricht, R

2006-06-12

Recent developments in DNA microarray technology led to a variety of open and closed devices and systems including high and low density microarrays for high-throughput screening applications as well as microarrays of lower density for specific diagnostic purposes. Beside predefined microarrays for specific applications manufacturers offer the production of custom-designed microarrays adapted to customers' wishes. Array based assays demand complex procedures including several steps for sample preparation (RNA extraction, amplification and sample labelling), hybridization and detection, thus leading to a high variability between several approaches and resulting in the necessity of extensive standardization and normalization procedures. In the present work a custom designed human proteinase DNA microarray of lower density in ArrayTube format was established. This highly economic open platform only requires standard laboratory equipment and allows the study of the molecular regulation of cell behaviour by proteinases. We established a procedure for sample preparation and hybridization and verified the array based gene expression profile by quantitative real-time PCR (QRT-PCR). Moreover, we compared the results with the well established Affymetrix microarray. By application of standard labelling procedures with e.g. Klenow fragment exo-, single primer amplification (SPA) or In Vitro Transcription (IVT) we noticed a loss of signal conservation for some genes. To overcome this problem we developed a protocol in accordance with the SPA protocol, in which we included target specific primers designed individually for each spotted oligomer. Here we present a complete array based assay in which only the specific transcripts of interest are amplified in parallel and in a linear manner. The array represents a proof of principle which can be adapted to other species as well. As the designed protocol for amplifying mRNA starts from as little as 100 ng total RNA, it presents an alternative method for detecting even low expressed genes by microarray experiments in a highly reproducible and sensitive manner. Preservation of signal integrity is demonstrated out by QRT-PCR measurements. The little amounts of total RNA necessary for the analyses make this method applicable for investigations with limited material as in clinical samples from, for example, organ or tumour biopsies. Those are arguments in favour of the high potential of our assay compared to established procedures for amplification within the field of diagnostic expression profiling. Nevertheless, the screening character of microarray data must be mentioned, and independent methods should verify the results.

The Role of Face Familiarity in Eye Tracking of Faces by Individuals with Autism Spectrum Disorders

ERIC Educational Resources Information Center

Sterling, Lindsey; Dawson, Geraldine; Webb, Sara; Murias, Michael; Munson, Jeffrey; Panagiotides, Heracles; Aylward, Elizabeth

2008-01-01

It has been shown that individuals with autism spectrum disorders (ASD) demonstrate normal activation in the fusiform gyrus when viewing familiar, but not unfamiliar faces. The current study utilized eye tracking to investigate patterns of attention underlying familiar versus unfamiliar face processing in ASD. Eye movements of 18 typically…

21 CFR 524.1200b - Kanamycin ophthalmic aqueous solution.

Code of Federal Regulations, 2011 CFR

2011-04-01

...) of this chapter. (c) Conditions of use. It is indicated for use in dogs in various eye infections due..., removal of foreign bodies, and intraocular surgery. Instill a few drops into the affected eye every 3... least 48 hours after the eye appears normal. For use only by or on the order of a licensed veterinarian...

21 CFR 524.1200a - Kanamycin ophthalmic ointment.

Code of Federal Regulations, 2011 CFR

2011-04-01

... for use in dogs in various eye infections due to kanamycin sensitive bacteria. It is used treating... the affected eye three or four times daily or more frequently if deemed advisable. Treatment should be continued for at least 48 hours after the eye appears normal. For use only by or on the order of a licensed...

21 CFR 524.1200b - Kanamycin ophthalmic aqueous solution.

Code of Federal Regulations, 2010 CFR

2010-04-01

...) of this chapter. (c) Conditions of use. It is indicated for use in dogs in various eye infections due..., removal of foreign bodies, and intraocular surgery. Instill a few drops into the affected eye every 3... least 48 hours after the eye appears normal. For use only by or on the order of a licensed veterinarian...

21 CFR 524.1200a - Kanamycin ophthalmic ointment.

Code of Federal Regulations, 2010 CFR

2010-04-01

... for use in dogs in various eye infections due to kanamycin sensitive bacteria. It is used treating... the affected eye three or four times daily or more frequently if deemed advisable. Treatment should be continued for at least 48 hours after the eye appears normal. For use only by or on the order of a licensed...

Evaluating reproducibility of differential expression discoveries in microarray studies by considering correlated molecular changes.

PubMed

Zhang, Min; Zhang, Lin; Zou, Jinfeng; Yao, Chen; Xiao, Hui; Liu, Qing; Wang, Jing; Wang, Dong; Wang, Chenguang; Guo, Zheng

2009-07-01

According to current consistency metrics such as percentage of overlapping genes (POG), lists of differentially expressed genes (DEGs) detected from different microarray studies for a complex disease are often highly inconsistent. This irreproducibility problem also exists in other high-throughput post-genomic areas such as proteomics and metabolism. A complex disease is often characterized with many coordinated molecular changes, which should be considered when evaluating the reproducibility of discovery lists from different studies. We proposed metrics percentage of overlapping genes-related (POGR) and normalized POGR (nPOGR) to evaluate the consistency between two DEG lists for a complex disease, considering correlated molecular changes rather than only counting gene overlaps between the lists. Based on microarray datasets of three diseases, we showed that though the POG scores for DEG lists from different studies for each disease are extremely low, the POGR and nPOGR scores can be rather high, suggesting that the apparently inconsistent DEG lists may be highly reproducible in the sense that they are actually significantly correlated. Observing different discovery results for a disease by the POGR and nPOGR scores will obviously reduce the uncertainty of the microarray studies. The proposed metrics could also be applicable in many other high-throughput post-genomic areas.

An evaluation of tyramide signal amplification and archived fixed and frozen tissue in microarray gene expression analysis

PubMed Central

Karsten, Stanislav L.; Van Deerlin, Vivianna M. D.; Sabatti, Chiara; Gill, Lisa H.; Geschwind, Daniel H.

2002-01-01

Archival formalin-fixed, paraffin-embedded and ethanol-fixed tissues represent a potentially invaluable resource for gene expression analysis, as they are the most widely available material for studies of human disease. Little data are available evaluating whether RNA obtained from fixed (archival) tissues could produce reliable and reproducible microarray expression data. Here we compare the use of RNA isolated from human archival tissues fixed in ethanol and formalin to frozen tissue in cDNA microarray experiments. Since an additional factor that can limit the utility of archival tissue is the often small quantities available, we also evaluate the use of the tyramide signal amplification method (TSA), which allows the use of small amounts of RNA. Detailed analysis indicates that TSA provides a consistent and reproducible signal amplification method for cDNA microarray analysis, across both arrays and the genes tested. Analysis of this method also highlights the importance of performing non-linear channel normalization and dye switching. Furthermore, archived, fixed specimens can perform well, but not surprisingly, produce more variable results than frozen tissues. Consistent results are more easily obtainable using ethanol-fixed tissues, whereas formalin-fixed tissue does not typically provide a useful substrate for cDNA synthesis and labeling. PMID:11788730

The multifocal electroretinogram in X-linked juvenile retinoschisis.

PubMed

Huang, Shizhou; Wu, Dezheng; Jiang, Futian; Luo, Guangwei; Liang, Jiongji; Wen, Feng; Yu, Minzhong; Long, Shixian; Wu, Lezheng

2003-05-01

To measure and compare the multifocal electroretinography in normal control and X-linked juvenile retinoschisis, 13 cases (13 right eyes) of normal control and nine cases (17 eyes) of X-linked juvenile retinoschisis were measured with VERIS Science 4.0. Four cases (eight eyes) out of the nine retinoschisis cases were tested with Ganzfeld ERG at the same day. The results showed statistically significant difference of average response densities and latencies in six ring retinal regions between the normal control and retinoschisis. The trace array and 3-D topography of multifocal ERG showed multi-area amplitude decrease with absence or reduction of central peak amplitude in patients with retinoschisis. The P1/N1 ratio of multifocal ERG average response densities in six ring retinal regions was different from the b/a ratio of Ganzfeld ERG. The multifocal ERG and Ganzfeld ERG each had its advantage in the diagnosis of retinoschisis.

Advanced Cancer Genomics Institute: Genetic Signatures and Therapeutic Targets in Cancer Progression

DTIC Science & Technology

2015-04-01

ORGANIZATION REPORT NUMBER Roswell Park Cancer Institute Elm and Carlton Streets Buffalo, NY 14263 9. SPONSORING / MONITORING AGENCY NAME(S) AND...AD- and CR-CaP cases. Roswell Park already has produced a 5- slide tumor microarray containing 722 CaP/matched normal biopsy samples for follow

Reading strategies in mild to moderate strabismic amblyopia: an eye movement investigation.

PubMed

Kanonidou, Evgenia; Proudlock, Frank A; Gottlob, Irene

2010-07-01

PURPOSE. To investigate oculomotor strategies in strabismic amblyopia and evaluate abnormalities during monocular and binocular reading. METHODS. Eye movements were recorded with a head-mounted infrared video eye-tracker (250 Hz, <0.01 degrees resolution) in 20 strabismic amblyopes (mean age, 44.9 +/- 10.7 years) and 20 normal control subjects (mean age, 42.8 +/- 10.9 years) while they silently read paragraphs of text. Monocular reading comparisons were made between the amblyopic eye and the nondominant eye of control subjects and the nonamblyopic eye and the dominant eye of the control subjects. Binocular reading between the amblyopic and control subjects was also compared. RESULTS. Mean reading speed, number of progressive and regressive saccades per line, saccadic amplitude (of progressive saccades), and fixation duration were estimated. Inter- and intrasubject statistical comparisons were made. Reading speed was significantly slower in amblyopes than in control subjects during monocular reading with amblyopic (13.094 characters/s vs. 22.188 characters/s; P < 0.0001) and nonamblyopic eyes (16.241 characters/s vs. 22.349 characters/s, P < 0.0001), and binocularly (15.698 characters/s vs. 23.425 characters/s, P < 0.0001). In amblyopes, reading was significantly slower with the amblyopic eye than with the nonamblyopic eye in binocular viewing (P < 0.05). These differences were associated with significantly more regressive saccades and longer fixation durations, but not with changes in saccadic amplitudes. CONCLUSIONS. In strabismic amblyopia, reading is impaired, not only during monocular viewing with the amblyopic eye, but also with the nonamblyopic eye and binocularly, even though normal visual acuity pertains to the latter two conditions. The impaired reading performance is associated with differences in both the saccadic and fixational patterns, most likely as adaptation strategies to abnormal sensory experiences such as crowding and suppression.

Eye movement perimetry in glaucoma.

PubMed

Trope, G E; Eizenman, M; Coyle, E

1989-08-01

Present-day computerized perimetry is often inaccurate and unreliable owing to the need to maintain central fixation over long periods while repressing the normal response to presentation of peripheral stimuli. We tested a new method of perimetry that does not require prolonged central fixation. During this test eye movements were encouraged on presentation of a peripheral target. Twenty-three eyes were studied with an Octopus perimeter, with a technician monitoring eye movements. The sensitivity was 100% and the specificity 23%. The low specificity was due to the technician's inability to accurately monitor small eye movements in the central 6 degrees field. If small eye movements are monitored accurately with an eye tracker, eye movement perimetry could become an alternative method to standard perimetry.

Estimation of the mechanical properties of the eye through the study of its vibrational modes

PubMed Central

2017-01-01

Measuring the eye’s mechanical properties in vivo and with minimally invasive techniques can be the key for individualized solutions to a number of eye pathologies. The development of such techniques largely relies on a computational modelling of the eyeball and, it optimally requires the synergic interplay between experimentation and numerical simulation. In Astrophysics and Geophysics the remote measurement of structural properties of the systems of their realm is performed on the basis of (helio-)seismic techniques. As a biomechanical system, the eyeball possesses normal vibrational modes encompassing rich information about its structure and mechanical properties. However, the integral analysis of the eyeball vibrational modes has not been performed yet. Here we develop a new finite difference method to compute both the spheroidal and, specially, the toroidal eigenfrequencies of the human eye. Using this numerical model, we show that the vibrational eigenfrequencies of the human eye fall in the interval 100 Hz–10 MHz. We find that compressible vibrational modes may release a trace on high frequency changes of the intraocular pressure, while incompressible normal modes could be registered analyzing the scattering pattern that the motions of the vitreous humour leave on the retina. Existing contact lenses with embebed devices operating at high sampling frequency could be used to register the microfluctuations of the eyeball shape we obtain. We advance that an inverse problem to obtain the mechanical properties of a given eye (e.g., Young’s modulus, Poisson ratio) measuring its normal frequencies is doable. These measurements can be done using non-invasive techniques, opening very interesting perspectives to estimate the mechanical properties of eyes in vivo. Future research might relate various ocular pathologies with anomalies in measured vibrational frequencies of the eye. PMID:28922351

Microarray-assisted fine-mapping of quantitative trait loci for cold tolerance in rice.

PubMed

Liu, Fengxia; Xu, Wenying; Song, Qian; Tan, Lubin; Liu, Jiayong; Zhu, Zuofeng; Fu, Yongcai; Su, Zhen; Sun, Chuanqing

2013-05-01

Many important agronomic traits, including cold stress resistance, are complex and controlled by quantitative trait loci (QTLs). Isolation of these QTLs will greatly benefit the agricultural industry but it is a challenging task. This study explored an integrated strategy by combining microarray with QTL-mapping in order to identify cold-tolerant QTLs from a cold-tolerant variety IL112 at early-seedling stage. All the early seedlings of IL112 survived normally for 9 d at 4-5°C, while Guichao2 (GC2), an indica cultivar, died after 4 d under the same conditions. Using the F2:3 population derived from the progeny of GC2 and IL112, we identified seven QTLs for cold tolerance. Furthermore, we performed Affymetrix rice whole-genome array hybridization and obtained the expression profiles of IL112 and GC2 under both low-temperature and normal conditions. Four genes were selected as cold QTL-related candidates, based on microarray data mining and QTL-mapping. One candidate gene, LOC_Os07g22494, was shown to be highly associated with cold tolerance in a number of rice varieties and in the F2:3 population, and its overexpression transgenic rice plants displayed strong tolerance to low temperature at early-seedling stage. The results indicated that overexpression of this gene (LOC_Os07g22494) could increase cold tolerance in rice seedlings. Therefore, this study provides a promising strategy for identifying candidate genes in defined QTL regions.

Genomic resources for songbird research and their use in characterizing gene expression during brain development

PubMed Central

Li, XiaoChing; Wang, Xiu-Jie; Tannenhauser, Jonathan; Podell, Sheila; Mukherjee, Piali; Hertel, Moritz; Biane, Jeremy; Masuda, Shoko; Nottebohm, Fernando; Gaasterland, Terry

2007-01-01

Vocal learning and neuronal replacement have been studied extensively in songbirds, but until recently, few molecular and genomic tools for songbird research existed. Here we describe new molecular/genomic resources developed in our laboratory. We made cDNA libraries from zebra finch (Taeniopygia guttata) brains at different developmental stages. A total of 11,000 cDNA clones from these libraries, representing 5,866 unique gene transcripts, were randomly picked and sequenced from the 3′ ends. A web-based database was established for clone tracking, sequence analysis, and functional annotations. Our cDNA libraries were not normalized. Sequencing ESTs without normalization produced many developmental stage-specific sequences, yielding insights into patterns of gene expression at different stages of brain development. In particular, the cDNA library made from brains at posthatching day 30–50, corresponding to the period of rapid song system development and song learning, has the most diverse and richest set of genes expressed. We also identified five microRNAs whose sequences are highly conserved between zebra finch and other species. We printed cDNA microarrays and profiled gene expression in the high vocal center of both adult male zebra finches and canaries (Serinus canaria). Genes differentially expressed in the high vocal center were identified from the microarray hybridization results. Selected genes were validated by in situ hybridization. Networks among the regulated genes were also identified. These resources provide songbird biologists with tools for genome annotation, comparative genomics, and microarray gene expression analysis. PMID:17426146

Prenatal diagnosis of fetuses with increased nuchal translucency using an approach based on quantitative fluorescent polymerase chain reaction and genomic microarray.

PubMed

Pan, Min; Han, Jin; Zhen, Li; Yang, Xin; Li, Ru; Liao, Can; Li, Dong-Zhi

2016-02-01

To assess the clinical value of prenatal diagnosis of fetuses with increased nuchal translucency (NT) using an approach based on quantitative fluorescent polymerase chain reaction (QF-PCR) and chromosomal microarray (CMA). From January 2013 to October 2014, we included 175 pregnancies with fetal NT ≥ 3.5mm at 11-13 weeks' gestation who received chorionic villus sampling. QF-PCR was first used to rapidly detect common aneuploidies. The cases with a normal QF-PCR result were analyzed by CMA. Of the 175 cases, common aneuploidies were detected by QF-PCR in 53 (30.2%) cases (30 cases of trisomy 21, 12 cases of monosomy X, 7 cases of trisomy 18, 3 cases of trisomy 13 and 1 case of 47, XXY). Among the 122 cases with a normal QF-PCR result, microarray detected additional pathogenic copy number variants (CNVs) in 5.7% (7/122) of cases. Four cases would have expected to be detectable by conventional karyotyping because of large deletions/duplications (>10 Mb), leaving three cases (2.5%; 3/118) with pathogenic CNVs only detectable by CMA. It is rational to use a diagnostic strategy in which CMA is preceded by the less expensive, rapid, QF-PCR to detect common aneuploidies. CMA allows detection of a number of pathogenic chromosomal aberrations in fetuses with a high NT. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Characterization of T-lymphocytes in the anterior uvea of eyes with chronic equine recurrent uveitis.

PubMed

Gilger, B C; Malok, E; Cutter, K V; Stewart, T; Horohov, D W; Allen, J B

1999-10-01

Equine recurrent uveitis (ERU), a chronic, recurrent inflammation primarily of the anterior uveal tract, is the most common cause of blindness in horses. Recently, T-lymphocytes have been found to be the most numerous cell type to infiltrate the anterior uveal of horses with ERU. In the present study, we characterized the T-lymphocyte population in the anterior uveal tract of eyes of horses with chronic ERU by evaluating the microscopic appearance (histopathologic features), the T-lymphocyte subsets, and the relative levels and amounts of T-lymphocyte cytokine mRNA in the anterior uvea. Seven inflamed eyes (from six horses with chronic ERU) and 5 normal eyes (from five horses with nonocular problems) were studied. After clinical examination, the eyes were removed, ocular fluids were aspirated, and anterior uveal tissues (iris and ciliary body) were processed for histologic and molecular (RNA isolation) analyses. Histologic examination by hematoxylin and eosin (H and E) staining and immunohistochemistry evaluating T-lymphocyte subsets (anti-CD4, CD8, CD5) were performed for each sample. RNA samples were analyzed for levels of messenger (m) RNA specific for interleukin (IL)-2, 4, and interferon-gamma (IFNgamma) by quantitative reverse transcriptase polymerase chain reaction (QRT-PCR). Eyes with ERU exhibited characteristic clinical signs, including corneal edema, aqueous flare, posterior synechia, corpora nigra degeneration, and cataract formation. Histologically, infiltration of the uveal tract with lymphocytes, plasma cells, and macrophages was most evident in the ciliary body and base of the iris. Loss of tissue structure (destruction) was most evident in the ciliary processes. Infiltrating lymphocytes were predominantly CD4+ T-cells (e.g. 48% CD4+ and 18% CD8+ in the ciliary body stroma), as determined by immunohistochemistry. Few inflammatory cells were observed in the normal eyes. The QRT-PCR results revealed increased transcription of IL-2 and IFNgamma and low IL-4 mRNA expression in eyes with chronic ERU compared to normal eyes, demonstrating a Thelper (Th) 1-like inflammatory response in eyes with ERU.

Rax: Developmental and Daily Expression Patterns in the Rat Pineal Gland and Retina

PubMed Central

Rohde, Kristian; Klein, David C.; Møller, Morten; Rath, Martin F.

2011-01-01

Retina and anterior neural fold homeobox (Rax) gene encodes a transcription factor essential for vertebrate eye development. Recent microarray studies indicate that Rax is expressed in the adult rat pineal gland and retina. The present study reveals that Rax expression levels in the rat change significantly during retinal development with a peak occurring at embryonic day (E) 18, whereas Rax expression in the pineal is relatively delayed and not detectable until E20. In both tissues, Rax is expressed throughout postnatal development into adulthood. In the mature rat pineal gland, the abundance of Rax transcripts increases 2-fold during the light period with a peak occurring at dusk. These findings are consistent with the evidence that Rax is of functional importance in eye development and suggest a role of Rax in the developing pineal gland. In addition, it would appear possible that Rax contributes to phenotype maintenance in the mature retina and pineal gland and may facilitate 24-h changes in the pineal transcriptome. PMID:21749377

Retrobulbar ocular blood flow changes measured by colour Doppler imaging after intra-arterial chemotherapy in retinoblastoma.

PubMed

Xue, Kang; Liu, Ailin; Hui, Ren; Zhang, Jing; Qian, Jiang

2017-10-01

To evaluate the effects of intra-arterial chemotherapy on retrobulbar blood flow parameters in patients with retinoblastoma. 20 eyes of 10 patients with unilateral retinoblastoma that were treated with intra-arterial chemotherapy were evaluated using colour Doppler imaging. The peak systolic and end-diastolic velocities of the ophthalmic, central retinal and posterior ciliary arteries were determined. The pulsatility and resistance indices were calculated automatically. The treated eye was compared with the untreated (control) eye and with itself before and after intra-arterial chemotherapy. When comparing the retinoblastoma-containing eyes with the contralateral normal eyes, the peak systolic and end-diastolic velocities of the central retinal artery were significantly higher in the tumorous eyes than in the normal eyes before intra-arterial chemotherapy. Moreover, the peak systolic and end-diastolic velocities in the posterior ciliary and central retinal arteries were significantly decreased after intra-arterial chemotherapy in the tumorous eyes (p<0.05). There were no statistically significant differences in the other parameters. Our results suggest that intra-arterial chemotherapy has a measurable effect on the retrobulbar blood flow, which can cause a decrease in the peak systolic and end-diastolic velocities in the posterior ciliary and central retinal arteries. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Intra-ocular pressure normalization technique and equipment

NASA Technical Reports Server (NTRS)

Baehr, E. F. (Inventor)

1979-01-01

A method and apparatus is described for safely reducing abnormally high intraocular pressure in an eye during a predetermined time interval. This allows maintenance of normal intraocular pressure during glaucoma surgery. A pressure regulator of the spring-biassed diaphragm type is provided with additional bias by a column of liquid. The hypodermic needle can be safely inserted into the anterior chamber of the eye. Liquid is then bled out of the column to reduce the bias on the diaphragm of the pressure regulator and, consequently, the output pressure of the regulator. This lowering pressure of the regulator also occurs in the eye by means of a small second bleed path provided between the pressure regulator and the hypodermic needle.

The eye movements of dyslexic children during reading and visual search: impact of the visual attention span.

PubMed

Prado, Chloé; Dubois, Matthieu; Valdois, Sylviane

2007-09-01

The eye movements of 14 French dyslexic children having a VA span reduction and 14 normal readers were compared in two tasks of visual search and text reading. The dyslexic participants made a higher number of rightward fixations in reading only. They simultaneously processed the same low number of letters in both tasks whereas normal readers processed far more letters in reading. Importantly, the children's VA span abilities related to the number of letters simultaneously processed in reading. The atypical eye movements of some dyslexic readers in reading thus appear to reflect difficulties to increase their VA span according to the task request.

Multimodal Imaging of the Normal Eye.

PubMed

Kawali, Ankush; Pichi, Francesco; Avadhani, Kavitha; Invernizzi, Alessandro; Hashimoto, Yuki; Mahendradas, Padmamalini

2017-10-01

Multimodal imaging is the concept of "bundling" images obtained from various imaging modalities, viz., fundus photograph, fundus autofluorescence imaging, infrared (IR) imaging, simultaneous fluorescein and indocyanine angiography, optical coherence tomography (OCT), and, more recently, OCT angiography. Each modality has its pros and cons as well as its limitations. Combination of multiple imaging techniques will overcome their individual weaknesses and give a comprehensive picture. Such approach helps in accurate localization of a lesion and understanding the pathology in posterior segment. It is important to know imaging of normal eye before one starts evaluating pathology. This article describes multimodal imaging modalities in detail and discusses healthy eye features as seen on various imaging modalities mentioned above.

Structural-metabolic organization of field 4 of the cat brain in normal conditions and after unilateral enucleation of the eye.

PubMed

Zykin, P A

2005-01-01

Comparative data on the structural-metabolic organization of field 4 of the cat brain in normal conditions and after unilateral enucleation of the eye are presented. Cytochrome oxidase was detected histochemically. Data were processed by a computerized method using an original video capture system. Data were obtained demonstrating the uneven distribution of enzyme along sublayer IlIb of field 4 in animals with unilateral enucleation. A hypothesis based on published data is suggested whereby the alternation of high- and low-reactive areas is evidence for the ordering of the retinal representations of the right and left eyes in the sensorimotor cortex.

Postural stability changes during large vertical diplopia induced by prism wear in normal subjects.

PubMed

Matsuo, Toshihiko; Yamasaki, Hanako; Yasuhara, Hirotaka; Hasebe, Kayoko

2013-01-01

To test the effect of double vision on postural stability, we measured postural stability by electric stabilometry before prism-wearing and immediately, 15, 30, and 60min after continuous prism-wearing with 6 prism diopters in total (a 3-prism-diopter prism placed with the base up in front of one eye and with the base down in front of the other eye) in 20 normal adult individuals with their eyes open or closed. Changes in stabilometric parameters in the time course of 60min were analyzed statistically by repeated-measure analysis of variance. When subjectsｾ eyes were closed, the total linear length (cm) and the unit-time length (cm/sec) of the sway path were significantly shortened during the 60-minute prism-wearing (p＜0.05). No significant change was noted in any stabilometric parameters obtained with the eyes open during the time course. In conclusion, postural stability did not change with the eyes open in the condition of large vertical diplopia, induced by prism-wearing for 60min, while the stability became better when measured with the eyes closed. A postural control mechanism other than that derived from visual input might be reinforced under abnormal visual input such as non-fusionable diplopia.

[Comparison of Discriminant Analysis and Decision Trees for the Detection of Subclinical Keratoconus].

PubMed

Kleinhans, Sonja; Herrmann, Eva; Kohnen, Thomas; Bühren, Jens

2017-08-15

Background Iatrogenic keratectasia is one of the most dreaded complications of refractive surgery. In most cases, keratectasia develops after refractive surgery of eyes suffering from subclinical stages of keratoconus with few or no signs. Unfortunately, there has been no reliable procedure for the early detection of keratoconus. In this study, we used binary decision trees (recursive partitioning) to assess their suitability for discrimination between normal eyes and eyes with subclinical keratoconus. Patients and Methods The method of decision tree analysis was compared with discriminant analysis which has shown good results in previous studies. Input data were 32 eyes of 32 patients with newly diagnosed keratoconus in the contralateral eye and preoperative data of 10 eyes of 5 patients with keratectasia after laser in-situ keratomileusis (LASIK). The control group was made up of 245 normal eyes after LASIK and 12-month follow-up without any signs of iatrogenic keratectasia. Results Decision trees gave better accuracy and specificity than did discriminant analysis. The sensitivity of decision trees was lower than the sensitivity of discriminant analysis. Conclusion On the basis of the patient population of this study, decision trees did not prove to be superior to linear discriminant analysis for the detection of subclinical keratoconus. Georg Thieme Verlag KG Stuttgart · New York.

Evaluation of eye injury risk from projectile shooting toys using the focus headform - biomed 2009.

PubMed

Bisplinghoff, Jill A; Duma, Stefan M

2009-01-01

Half of eye injuries in the United States are caused by a blunt impact and more specifically, eye injuries effecting children often result from projectile shooting toys. The purpose of this study is to evaluate the risk of eye injuries of currently available projectile shooting toys. In order to assess the risk of each toy, a Facial and Ocular Countermeasure Safety (FOCUS) headform was used to measure the force applied to the eye during each hit for a total of 18 tests. The selected toys included a dart gun, a foam launcher, and a ball launcher. The force ranged from 4-93 N and was analyzed using the injury risk function for globe rupture for the FOCUS headform. Projectile characteristics were also examined using normalized energy to determine risk of corneal abrasion, hyphema, lens dislocation, retinal damage and globe rupture. It was found that the three toys tested produced peak loads corresponding with risk of globe rupture between 0% and 17.3%. The normalized energy results show no risk of hyphema, lens dislocation, retinal damage or globe rupture and a maximum risk of corneal abrasion of 5.9%. This study concludes that although there are many eye injuries caused by projectiles, the selected toys show a very low risk of eye injury.

Ultrasonographic biometry of the normal eye of the Persian cat.

PubMed

Mirshahi, A; Shafigh, S H; Azizzadeh, M

2014-07-01

To describe the normal ultrasonographic biometry of the Persian cat's eyes using B-mode ultrasonography. In a cross-sectional study, 20 healthy Persian cats with no history of previous ophthalmic disease were examined. Ocular biometry of the left and right eyes was measured using B-mode ultrasonography. Comparison of the average measurements between left and right eyes and between vertical and horizontal planes was performed using paired-sample t test. Correlation of ocular parameters with sex, age, head circumference and eye colour was evaluated. Mean ± standard deviation (SD) measurements of the ocular structures of anterior chamber, lens thickness, vitreous chamber and anterior to posterior dimension of the globe in 40 eyes were 4.1 ± 0.7, 7.7 ± 0.5, 8.2 ± 0.4 and 20.7 ± 1.0 mm, respectively. No significant difference was found between the ocular biometry of the left and right eyes or the horizontal and vertical planes. Of the ocular parameters, the following had a significant positive correlation with head circumference: axial globe length, anterior chamber and lens thickness. The vitreous body had a positive correlation with age. Regarding the breed predisposition of Persian cats to ocular problems, the present study provides baseline information for further clinical investigations of ocular abnormalities using B-mode ultrasonography. © 2014 Australian Veterinary Association.

Normal correspondence of tectal maps for saccadic eye movements in strabismus

PubMed Central

Economides, John R.; Adams, Daniel L.

2016-01-01

The superior colliculus is a major brain stem structure for the production of saccadic eye movements. Electrical stimulation at any given point in the motor map generates saccades of defined amplitude and direction. It is unknown how this saccade map is affected by strabismus. Three macaques were raised with exotropia, an outwards ocular deviation, by detaching the medial rectus tendon in each eye at age 1 mo. The animals were able to make saccades to targets with either eye and appeared to alternate fixation freely. To probe the organization of the superior colliculus, microstimulation was applied at multiple sites, with the animals either free-viewing or fixating a target. On average, microstimulation drove nearly conjugate saccades, similar in both amplitude and direction but separated by the ocular deviation. Two monkeys showed a pattern deviation, characterized by a systematic change in the relative position of the two eyes with certain changes in gaze angle. These animals' saccades were slightly different for the right eye and left eye in their amplitude or direction. The differences were consistent with the animals' underlying pattern deviation, measured during static fixation and smooth pursuit. The tectal map for saccade generation appears to be normal in strabismus, but saccades may be affected by changes in the strabismic deviation that occur with different gaze angles. PMID:27605534

Dry eye and meibomian gland dysfunction in pseudophakic bullous keratopathy.

PubMed

Palamar, Melis; Kiyat, Pelin; Yagci, Ayse

2018-02-01

To evaluate dry eye tests and meibography of patients with pseudophakic bullous keratopathy (PBK). Thirty-seven patients with PBK were included. The eyes with PBK were compared with the normal pseudophakic fellow eyes. All patients had undergone a detailed ophthalmic examination including corneal and conjunctival fluorescein staining and Oxford scoring, tear film breakup time, Schirmer 1 test, Ocular Surface Disease Index (OSDI) score assessment, lid margin abnormalities, upper and lower eyelid Meibomian gland evaluation using infrared captures of a biomicroscope. Partial or complete loss of the Meibomian glands (Meibomian dropout) was scored for each eyelid from grade 0 (no loss) through grade 3 (lost area was > 2/3 of the total meibomian gland area). The mean age of the patients was 73.2 ± 8.9 (range, 50-93). Mean tear film breakup time value was statistically lower in PBK eyes (P ≤ 0.001). OSDI, Oxford, lid margin abnormalities, inferior meibography, total meibography score were significantly higher in PBK eyes (P ≤ 0.001). The comparison of Schirmer 1 and superior meibography scores of the groups was insignificant (P = 0.143, P = 0.793, respectively). The Meibomian gland morphology of the PBK eyes demonstrates significant differences when compared with normal fellow eyes and might be related to evaporative dry eye. For this reason, patients with PBK should be monitored for Meibomian gland dysfunction and when needed start prompt treatment in order to prevent further disturbance of the ocular surface.

Degree and duration of corneal anesthesia after topical application of 0.4% oxybuprocaine hydrochloride ophthalmic solution in ophthalmically normal dogs.

PubMed

Douet, Jean-Yves; Michel, Julien; Regnier, Alain

2013-10-01

To assess the anesthetic efficacy and local tolerance of topically applied 0.4% oxybuprocaine ophthalmic solution to in dogs and compare its effects with those of 1% tetracaine solution. 34 ophthalmically normal Beagles. Dogs were assigned to 2 groups, and baseline corneal touch threshold (CTT) was measured bilaterally with a Cochet-Bonnet aesthesiometer. Dogs of group 1 (n = 22) received a single drop of 0.4% oxybuprocaine ophthalmic solution in one eye and saline (0.9% NaCl) solution (control treatment) in the contralateral eye. Dogs of group 2 (n = 12) received a single drop of 0.4% oxybuprocaine ophthalmic solution in one eye and 1% tetracaine ophthalmic solution in the contralateral eye. The CTT of each eye was measured 1 and 5 minutes after topical application and then at 5-minute intervals until 75 minutes after topical application. CTT changes over time differed significantly between oxybuprocaine-treated and control eyes. After instillation of oxybuprocaine, maximal corneal anesthesia (CTT = 0) was achieved within 1 minute, and CTT was significantly decreased from 1 to 45 minutes, compared with the baseline value. No significant difference in onset, depth, and duration of corneal anesthesia was found between oxybuprocaine-treated and tetracaine-treated eyes. Conjunctival hyperemia and chemosis were detected more frequently in tetracaine-treated eyes than in oxybuprocaine-treated eyes. Topical application of oxybuprocaine and tetracaine similarly reduced corneal sensitivity in dogs, but oxybuprocaine was less irritating to the conjunctiva than was tetracaine.

Transcriptome analysis of the planarian eye identifies ovo as a specific regulator of eye regeneration

PubMed Central

Lapan, Sylvain W.; Reddien, Peter W.

2013-01-01

Summary Among the millions of invertebrate species with visual systems, the genetic basis of eye development and function is well understood only in Drosophila melanogaster. We describe an eye transcriptome for the planarian Schmidtea mediterranea. Planarian photoreceptors expressed orthologs of genes required for phototransduction and microvillus structure in Drosophila and vertebrates, and optic pigment cells expressed solute transporters and melanin synthesis enzymes similar to those active in the vertebrate retinal pigment epithelium. Orthologs of several planarian eye genes, such as bestrophin-1 and Usher syndrome genes, cause eye defects in mammals when perturbed and were not previously described to have roles in invertebrate eyes. Five previously undescribed planarian eye transcription factors were required for normal eye formation during head regeneration. In particular, a conserved, transcription factor-encoding ovo gene was expressed from the earliest stages of eye regeneration and was required for regeneration of all cell types of the eye. PMID:22884275

A Spiking Strategy for ChIP-chip Data Normalization in S. cerevisiae.

PubMed

Jeronimo, Célia; Robert, François

2017-01-01

Chromatin immunoprecipitation coupled to DNA microarrays (ChIP-chip) is widely used in the chromatin field, notably to map the position of histone variants or histone modifications along the genome. Often, the position and the occupancy of these epigenetic marks are to be compared between different experiments. It is now increasingly recognized that such cross-sample comparison is better done using externally added exogenous controls for normalization but no such method has been described for ChIP-chip. Here we describe a spiking normalization strategy that makes use of phiX174 phage DNA as a spiked control for normalization of ChIP-chip signals across different experiments.

The Porcelain Crab Transcriptome and PCAD, the Porcelain Crab Microarray and Sequence Database

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tagmount, Abderrahmane; Wang, Mei; Lindquist, Erika

2010-01-27

Background: With the emergence of a completed genome sequence of the freshwater crustacean Daphnia pulex, construction of genomic-scale sequence databases for additional crustacean sequences are important for comparative genomics and annotation. Porcelain crabs, genus Petrolisthes, have been powerful crustacean models for environmental and evolutionary physiology with respect to thermal adaptation and understanding responses of marine organisms to climate change. Here, we present a large-scale EST sequencing and cDNA microarray database project for the porcelain crab Petrolisthes cinctipes. Methodology/Principal Findings: A set of ~;;30K unique sequences (UniSeqs) representing ~;;19K clusters were generated from ~;;98K high quality ESTs from a set ofmore » tissue specific non-normalized and mixed-tissue normalized cDNA libraries from the porcelain crab Petrolisthes cinctipes. Homology for each UniSeq was assessed using BLAST, InterProScan, GO and KEGG database searches. Approximately 66percent of the UniSeqs had homology in at least one of the databases. All EST and UniSeq sequences along with annotation results and coordinated cDNA microarray datasets have been made publicly accessible at the Porcelain Crab Array Database (PCAD), a feature-enriched version of the Stanford and Longhorn Array Databases.Conclusions/Significance: The EST project presented here represents the third largest sequencing effort for any crustacean, and the largest effort for any crab species. Our assembly and clustering results suggest that our porcelain crab EST data set is equally diverse to the much larger EST set generated in the Daphnia pulex genome sequencing project, and thus will be an important resource to the Daphnia research community. Our homology results support the pancrustacea hypothesis and suggest that Malacostraca may be ancestral to Branchiopoda and Hexapoda. Our results also suggest that our cDNA microarrays cover as much of the transcriptome as can reasonably be captured in EST library sequencing approaches, and thus represent a rich resource for studies of environmental genomics.« less

Evaluation of external RNA controls for the standardisation of gene expression biomarker measurements.

PubMed

Devonshire, Alison S; Elaswarapu, Ramnath; Foy, Carole A

2010-11-24

Gene expression profiling is an important approach for detecting diagnostic and prognostic biomarkers, and predicting drug safety. The development of a wide range of technologies and platforms for measuring mRNA expression makes the evaluation and standardization of transcriptomic data problematic due to differences in protocols, data processing and analysis methods. Thus, universal RNA standards, such as those developed by the External RNA Controls Consortium (ERCC), are proposed to aid validation of research findings from diverse platforms such as microarrays and RT-qPCR, and play a role in quality control (QC) processes as transcriptomic profiling becomes more commonplace in the clinical setting. Panels of ERCC RNA standards were constructed in order to test the utility of these reference materials (RMs) for performance characterization of two selected gene expression platforms, and for discrimination of biomarker profiles between groups. The linear range, limits of detection and reproducibility of microarray and RT-qPCR measurements were evaluated using panels of RNA standards. Transcripts of low abundance (≤ 10 copies/ng total RNA) showed more than double the technical variability compared to higher copy number transcripts on both platforms. Microarray profiling of two simulated 'normal' and 'disease' panels, each consisting of eight different RNA standards, yielded robust discrimination between the panels and between standards with varying fold change ratios, showing no systematic effects due to different labelling and hybridization runs. Also, comparison of microarray and RT-qPCR data for fold changes showed agreement for the two platforms. ERCC RNA standards provide a generic means of evaluating different aspects of platform performance, and can provide information on the technical variation associated with quantification of biomarkers expressed at different levels of physiological abundance. Distinct panels of standards serve as an ideal quality control tool kit for determining the accuracy of fold change cut-off threshold and the impact of experimentally-derived noise on the discrimination of normal and disease profiles.

Use of homologous and heterologous gene expression profiling tools to characterize transcription dynamics during apple fruit maturation and ripening.

PubMed

Costa, Fabrizio; Alba, Rob; Schouten, Henk; Soglio, Valeria; Gianfranceschi, Luca; Serra, Sara; Musacchi, Stefano; Sansavini, Silviero; Costa, Guglielmo; Fei, Zhangjun; Giovannoni, James

2010-10-25

Fruit development, maturation and ripening consists of a complex series of biochemical and physiological changes that in climacteric fruits, including apple and tomato, are coordinated by the gaseous hormone ethylene. These changes lead to final fruit quality and understanding of the functional machinery underlying these processes is of both biological and practical importance. To date many reports have been made on the analysis of gene expression in apple. In this study we focused our investigation on the role of ethylene during apple maturation, specifically comparing transcriptomics of normal ripening with changes resulting from application of the hormone receptor competitor 1-methylcyclopropene. To gain insight into the molecular process regulating ripening in apple, and to compare to tomato (model species for ripening studies), we utilized both homologous and heterologous (tomato) microarray to profile transcriptome dynamics of genes involved in fruit development and ripening, emphasizing those which are ethylene regulated.The use of both types of microarrays facilitated transcriptome comparison between apple and tomato (for the later using data previously published and available at the TED: tomato expression database) and highlighted genes conserved during ripening of both species, which in turn represent a foundation for further comparative genomic studies. The cross-species analysis had the secondary aim of examining the efficiency of heterologous (specifically tomato) microarray hybridization for candidate gene identification as related to the ripening process. The resulting transcriptomics data revealed coordinated gene expression during fruit ripening of a subset of ripening-related and ethylene responsive genes, further facilitating the analysis of ethylene response during fruit maturation and ripening. Our combined strategy based on microarray hybridization enabled transcriptome characterization during normal climacteric apple ripening, as well as definition of ethylene-dependent transcriptome changes. Comparison with tomato fruit maturation and ethylene responsive transcriptome activity facilitated identification of putative conserved orthologous ripening-related genes, which serve as an initial set of candidates for assessing conservation of gene activity across genomes of fruit bearing plant species.

Evaluation of microarray data normalization procedures using spike-in experiments

PubMed Central

Rydén, Patrik; Andersson, Henrik; Landfors, Mattias; Näslund, Linda; Hartmanová, Blanka; Noppa, Laila; Sjöstedt, Anders

2006-01-01

Background Recently, a large number of methods for the analysis of microarray data have been proposed but there are few comparisons of their relative performances. By using so-called spike-in experiments, it is possible to characterize the analyzed data and thereby enable comparisons of different analysis methods. Results A spike-in experiment using eight in-house produced arrays was used to evaluate established and novel methods for filtration, background adjustment, scanning, channel adjustment, and censoring. The S-plus package EDMA, a stand-alone tool providing characterization of analyzed cDNA-microarray data obtained from spike-in experiments, was developed and used to evaluate 252 normalization methods. For all analyses, the sensitivities at low false positive rates were observed together with estimates of the overall bias and the standard deviation. In general, there was a trade-off between the ability of the analyses to identify differentially expressed genes (i.e. the analyses' sensitivities) and their ability to provide unbiased estimators of the desired ratios. Virtually all analysis underestimated the magnitude of the regulations; often less than 50% of the true regulations were observed. Moreover, the bias depended on the underlying mRNA-concentration; low concentration resulted in high bias. Many of the analyses had relatively low sensitivities, but analyses that used either the constrained model (i.e. a procedure that combines data from several scans) or partial filtration (a novel method for treating data from so-called not-found spots) had with few exceptions high sensitivities. These methods gave considerable higher sensitivities than some commonly used analysis methods. Conclusion The use of spike-in experiments is a powerful approach for evaluating microarray preprocessing procedures. Analyzed data are characterized by properties of the observed log-ratios and the analysis' ability to detect differentially expressed genes. If bias is not a major problem; we recommend the use of either the CM-procedure or partial filtration. PMID:16774679

Normal Morning Melanin-Concentrating Hormone Levels and No Association with Rapid Eye Movement or Non-Rapid Eye Movement Sleep Parameters in Narcolepsy Type 1 and Type 2

PubMed Central

Schrölkamp, Maren; Jennum, Poul J.; Gammeltoft, Steen; Holm, Anja; Kornum, Birgitte R.; Knudsen, Stine

2017-01-01

Study Objectives: Other than hypocretin-1 (HCRT-1) deficiency in narcolepsy type 1 (NT1), the neurochemical imbalance of NT1 and narcolepsy type 2 (NT2) with normal HCRT-1 levels is largely unknown. The neuropeptide melanin-concentrating hormone (MCH) is mainly secreted during sleep and is involved in rapid eye movement (REM) and non-rapid eye movement (NREM) sleep regulation. Hypocretin neurons reciprocally interact with MCH neurons. We hypothesized that altered MCH secretion contributes to the symptoms and sleep abnormalities of narcolepsy and that this is reflected in morning cerebrospinal fluid (CSF) MCH levels, in contrast to previously reported normal evening/afternoon levels. Methods: Lumbar CSF and plasma were collected from 07:00 to 10:00 from 57 patients with narcolepsy (subtypes: 47 NT1; 10 NT2) diagnosed according to International Classification of Sleep Disorders, Third Edition (ICSD-3) and 20 healthy controls. HCRT-1 and MCH levels were quantified by radioimmunoassay and correlated with clinical symptoms, polysomnography (PSG), and Multiple Sleep Latency Test (MSLT) parameters. Results: CSF and plasma MCH levels were not significantly different between narcolepsy patients regardless of ICSD-3 subtype, HCRT-1 levels, or compared to controls. CSF MCH and HCRT-1 levels were not significantly correlated. Multivariate regression models of CSF MCH levels, age, sex, and body mass index predicting clinical, PSG, and MSLT parameters did not reveal any significant associations to CSF MCH levels. Conclusions: Our study shows that MCH levels in CSF collected in the morning are normal in narcolepsy and not associated with the clinical symptoms, REM sleep abnormalities, nor number of muscle movements during REM or NREM sleep of the patients. We conclude that morning lumbar CSF MCH measurement is not an informative diagnostic marker for narcolepsy. Citation: Schrölkamp M, Jennum PJ, Gammeltoft S, Holm A, Kornum BR, Knudsen S. Normal morning melanin-concentrating hormone levels and no association with rapid eye movement or non-rapid eye movement sleep parameters in narcolepsy type 1 and type 2. J Clin Sleep Med. 2017;13(2):235–243. PMID:27855741

Prevalence of Undiagnosed Age-Related Macular Degeneration in Primary Eye Care.

PubMed

Neely, David C; Bray, Kevin J; Huisingh, Carrie E; Clark, Mark E; McGwin, Gerald; Owsley, Cynthia

2017-06-01

Age-related macular degeneration (AMD) is the leading cause of irreversible vision impairment in older adults in the United States, yet little is known about whether AMD is appropriately diagnosed in primary eye care. To examine the prevalence of eyes with AMD in patients seen in primary eye care clinics who purportedly have normal macular health per their medical record and the association of AMD with patient and physician characteristics. In this cross-sectional study of primary eye care practices in Birmingham, Alabama, 644 persons 60 years or older with normal macular health per medical record based on their most recent dilated comprehensive eye examination by a primary eye care ophthalmologist or optometrist were enrolled from May 1, 2009, through December 31, 2011. Data analysis was performed from May 1, 2016, through December 20, 2016. Presence of AMD as defined by the Clinical Age-Related Maculopathy Staging system based on color fundus photography and a masked grader. Types of AMD-associated lesions were noted. Patient health and physician characteristics were collected. The sample consisted of 1288 eyes from 644 participants (231 [35.9%] male and 413 [64.1%] female; mean [SD] age, 69.4 [6.1] years; 611 white [94.9%]) seen by 31 primary eye care ophthalmologists or optometrists. A total of 968 eyes (75.2%) had no AMD, in agreement with their medical record; 320 (24.8%) had AMD despite no diagnosis of AMD in the medical record. Among eyes with undiagnosed AMD, 32 (10.0%) had hyperpigmentation, 43 (13.4%) had hypopigmentation, 249 (77.8%) had small drusen, 250 (78.1%) had intermediate drusen, and 96 (30.0%) had large drusen. Undiagnosed AMD was associated with older patient age (odds ratio [OR], 1.06; 95% CI, 1.04-1.09; P < .001), male sex (age-adjusted OR, 1.39; 95% CI, 1.02-1.91; P = .04), and less than a high school education (age-adjusted OR, 2.40; 95% CI, 1.03-5.62; P = .04). Prevalence of undiagnosed AMD was not different for ophthalmologists and optometrists (age adjusted OR, 0.99; 95% CI, 0.71-1.36; P = .94). Approximately 25.0% of eyes deemed to be normal based on dilated eye examination by primary eye care physicians had macular characteristics that indicated AMD revealed by fundus photography and trained raters. A total of 30.0% of eyes with undiagnosed AMD had AMD with large drusen that would have been treatable with nutritional supplements had it been diagnosed. Improved AMD detection strategies may be needed in primary eye care as more effective treatment strategies for early AMD become available in the coming years.

Expression of a chemokine by ciliary body epithelium in horses with naturally occurring recurrent uveitis and in cultured ciliary body epithelial cells.

PubMed

Gilger, Brian C; Yang, Ping; Salmon, Jacklyn H; Jaffe, Glenn J; Allen, Janice B

2002-07-01

To determine whether a chemokine (RANTES)-like protein expressed by ciliary epithelium plays a role in uveitis. 3 clinically normal horses intradermal, 5 eyes from 5 horses with recurrent uveitis, and 10 normal eyes from 5 age- and sex-matched horses. Cross-reactivity and sensitivity of recombinant human (rh)-regulated upon activation, normal T-cell expressed and secreted (RANTES) protein were evaluated in horses by use of intradermal hypersensitivity reactions and a chemotaxis assay. Aqueous humor and ciliary body of eyes from clinically normal horses and horses with uveitis were examined for RANTES expression by use of an ELISA and reverse transcription-polymerase chain reaction (RT-PCR). Expression of RANTES mRNA and protein content of primary cultures of equine ciliary pigmented epithelial cells (RT-PCR) and culture supernatant (ELISA) were measured 6 or 24 hours, respectively, after cultures were stimulated with interleukin-1beta and tumor necrosis factor-alpha. Strong reactions to intradermal hypersensitivity testing and significant chemotaxis of equine leukocytes to rh-RANTES wereas observed. Aqueous humor of eyes from horses with uveitis contained increased concentrations of rh-RANTES-like protein (mean +/- SD, 45.9+/-31.7 pg/ml), compared with aqueous humor from clinically normal horses (0 pg/ml). Ciliary body from horses with uveitis expressed RANTES mRNA, whereas ciliary body from clinically normal horses had low mRNA expression. Stimulated ciliary pigmented epithelial cells expressed increased amounts of rh-RANTES-like protein (506.1+/-298.3 pg/ml) and mRNA, compared with unstimulated samples. Ciliary epithelium may play a role in recruitment and activation of leukocytes through expression of RANTES.

In utero mouse embryonic imaging with OCT for ophthalmologic research

NASA Astrophysics Data System (ADS)

Syed, Saba H.; Larina, Irina V.; Dickinson, Mary E.; Larin, Kirill V.

2011-03-01

Live imaging of an eye during embryonic development in mammalian model is important for understanding dynamic aspects of normal and abnormal eye morphogenesis. In this study, we used Swept Source Optical Coherence Tomography (SS-OCT) for live structural imaging of mouse embryonic eye through the uterine wall. The eye structure was reconstructed in mouse embryos at 13.5 to 17.5 days post coitus (dpc). Despite the limited imaging depth of OCT in turbid tissues, we were able to visualize the whole eye globe at these stages. These results suggest that live in utero OCT imaging is a useful tool to study embryonic eye development in the mouse model.

Cataract surgery in eyes with low corneal endothelial cell density.

PubMed

Hayashi, Ken; Yoshida, Motoaki; Manabe, Shin-ichi; Hirata, Akira

2011-08-01

To compare corneal endothelial damage after cataract surgery in eyes with low endothelial cell density (ECD) and eyes with normal ECD. Hayashi Eye Hospital, Fukuoka, Japan. Case-control study. Cataract surgery was performed in eyes with a low ECD (500 to 1000 cells/mm(2)) (low-density group) and control eyes with a normal ECD. The ECD and central corneal thickness (CCT) were measured preoperatively and 1 and 3 months postoperatively, and the percentage cell loss and increase in CCT were compared. The low-density group and control group each comprised 50 eyes. In the low-density group, 39 eyes had nonprogressive endothelial pathology and 11 had Fuchs dystrophy. The mean ECD was significantly less and the CCT significantly greater in the low-density group than in the control group throughout the follow-up (P ≤.0066). However, no significant difference in the percentage of cell loss was found between groups at 1 or 3 months (5.1%, low-density group; 4.2%, control group) (P ≥.1477). The percentage increase in CCT was significantly greater in the low-density group than in the control group at 1 month (P<.0001), although there was no significant difference at 3 months (0.4% and -0.4%, respectively) (P=.2172). Corneal endothelial damage after cataract surgery in eyes with low ECD was slight and comparable to that in healthy eyes, which suggests that cataract surgery alone (without corneal transplantation) should be performed first. Copyright © 2011 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

Genetics Home Reference: horizontal gaze palsy with progressive scoliosis

MedlinePlus

... to track moving objects. Up-and-down (vertical) eye movements are typically normal. In people with HGPPS , an ... the brainstem is the underlying cause of the eye movement abnormalities associated with the disorder. The cause of ...

The zoom lens of attention: Simulating shuffled versus normal text reading using the SWIFT model

PubMed Central

Schad, Daniel J.; Engbert, Ralf

2012-01-01

Assumptions on the allocation of attention during reading are crucial for theoretical models of eye guidance. The zoom lens model of attention postulates that attentional deployment can vary from a sharp focus to a broad window. The model is closely related to the foveal load hypothesis, i.e., the assumption that the perceptual span is modulated by the difficulty of the fixated word. However, these important theoretical concepts for cognitive research have not been tested quantitatively in eye movement models. Here we show that the zoom lens model, implemented in the SWIFT model of saccade generation, captures many important patterns of eye movements. We compared the model's performance to experimental data from normal and shuffled text reading. Our results demonstrate that the zoom lens of attention might be an important concept for eye movement control in reading. PMID:22754295

Congenital disorder of true cyclopia with polydactylia: case report and review of the literature.

PubMed

Deftereou, T E; Tsoulopoulos, V; Alexiadis, G; Papadopoulos, E; Chouridou, E; Katotomichelakis, M; Lambropoulou, M

2013-01-01

Cyclopia is a rare type of holoprosencephaly and a congenital disorder characterized by the failure of the embryonic forebrain to properly divide the orbits of the eye into two cavities (the embryonic forebrain is normally responsible for inducing the development of the orbits). As a result a birth defect in which there is only one eye is developed. This eye is centrally placed in the area normally occupied by the root of the nose. As a rule, there is a missing nose or a non-functioning nose in the form of a proboscis (a tubular appendage) located above the central eye. In this report the macroscopic, radiographic, and immunohistochemical findings of a case of true cyclopia in a female fetus are described. Cyclopia is a lethal condition that is associated with dramatic symmetric deformities of the nose, skull, orbits, and brain.

Waardenburg-Shah Syndrome: a rare case in an Indian child.

PubMed

Pattebahadur, Rajesh; Singhi, Shipra; Maharana, Prafulla Kumar

2016-09-30

A 7-year-old male child presented with a history of discolouration of right eye since birth. On examination visual acuity was 6/6 on Snellen's chart in both eyes; anterior segment was within normal limits except for the brilliant blue discolouration of the inferior quadrant and superior quadrant of right iris and left eye iris, respectively. Both eyes had a clear lens and fundus findings were within normal limits. A detailed history from parents revealed that the child had difficulty in hearing and slurring of speech. In addition, the child had repeated episodes of constipation with bilious vomiting during infancy for which a diagnosis of fungal sepsis with Hirschsprung's disease was made and the child had to undergo a mid-sigmoid loop colostomy for that. A diagnosis of Waardenburg--Shah Syndrome was made and the child was referred for hearing and speech rehabilitation. 2016 BMJ Publishing Group Ltd.

Benzodiazepine sensitivity in normal human subjects.

PubMed

Hommer, D W; Matsuo, V; Wolkowitz, O; Chrousos, G; Greenblatt, D J; Weingartner, H; Paul, S M

1986-06-01

Increasing intravenous doses of diazepam or placebo were administered to ten healthy normal volunteers, and the changes in saccadic eye velocity, self-rated sedation and anxiety, and plasma cortisol and growth hormone concentrations were measured. Diazepam administration (4.4 to 140 micrograms/kg, cumulative dose) resulted in a dose-dependent decrease in saccadic eye velocity and plasma cortisol level as well as a dose-dependent increase in self-rated sedation and plasma growth hormone level. Self-rated anxiety was unaffected in these relatively nonanxious subjects. The diazepam-induced changes in saccadic eye velocity, sedation, and growth hormone and cortisol levels were highly correlated with each other and with increasing plasma diazepam concentration. These results are consistent with a benzodiazepine receptor-mediated action of diazepam. The highly quantifiable and dose-dependent decrease in saccadic eye velocity by benzodiazepines should make this a useful measure of benzodiazepine receptor sensitivity in humans.

Brightness discrimination and contrast sensitivity in chronic glaucoma--a clinical study.

PubMed

Teoh, S L; Allan, D; Dutton, G N; Foulds, W S

1990-04-01

The visual acuity, the difference in sensitivity of the two eyes to light (brightness ratio), and contrast sensitivity were assessed in 28 patients with chronic open angle glaucoma and compared with those of 41 normal controls of similar ages and visual acuity. The results obtained were related to the results of Tübingen visual field analysis in patients with glaucoma. Twenty-four of the 28 glaucoma patients (86%) had a significant disparity in brightness ratio between the two eyes. This was found to match the frequency of visual field loss. Moreover, there was a significant relationship between the interocular differences in brightness sense and the difference in the degree of visual field loss between the two eyes. Of the glaucoma patients 39% had sum contrast sensitivities outside the normal range for age-matched normal controls. No significant correlation was found between the interocular difference in brightness sense and the visual acuity or the interocular difference in sum contrast sensitivity. It is concluded that, in the presence of a normal visual acuity, the brightness ratio test warrants evaluation as a potential screening test for chronic open angle glaucoma.

Effect of gravitoinertial force on ocular counterrolling.

NASA Technical Reports Server (NTRS)

Miller, E. F., II; Graybiel, A.

1971-01-01

The effect of G loading on the magnitude of ocular counterrolling at various angles of tilt up to 63 deg. was measured on normal subjects and compared with the effect on persons with severe or complete loss of vestibular function. The group of six normal subjects manifested a compensatory eye roll which increased as a direct and essentially linear function of the component of the gravitoinertial force acting laterally on the subject. This increase in response was not observed in the five deaf subjects with severe or complete bilateral loss of their vestibular organs. These findings confirmed similar results found by other authors using other measuring techniques which show that the reflex eye movement is dependent on and limited to the magnitude of the gravitoinertial stimulus (within the range used) when the otolithocular system is functioning normally. However when this function is severely impaired or lost, the magnitude of the compensatory eye roll is limited to that manifested at 1 G and possibly to nonotolithic contributions. These findings offer means for differentiation between otolithic-defective and ?normal' persons who exhibit little counterrolling.

Eye development and the appearance and maintenance of corneal transparency

NASA Technical Reports Server (NTRS)

Conrad, G. W.; Funderburgh, J. L.; Spooner, B. S. (Principal Investigator)

1992-01-01

Embryonic development of the eye, including the cornea, depends on the appearance and steady maintenance of intraocular pressure. The eye is a gravity-sensitive organ, as evidence by changes in pupil diameter during parabolic flight. The cornea is largely a paracrystal of extracellular matrix. The extent to which it will polymerize normally in microgravity has yet to be determined.

Eye-Hand Coordination in Children with High Functioning Autism and Asperger's Disorder Using a Gap-Overlap Paradigm

ERIC Educational Resources Information Center

Crippa, Alessandro; Forti, Sara; Perego, Paolo; Molteni, Massimo

2013-01-01

We investigated eye-hand coordination in children with autism spectrum disorders (ASD) in comparison with age-matched normally developing peers. The eye-hand correlation was measured by putting fixation latencies in relation with pointing and key pressing responses in visual detection tasks where a gap-overlap paradigm was used and compared to…

Improvement of horizontal macular contraction after surgical removal of epiretinal membranes.

PubMed

Yang, H K; Kim, S J; Jung, Y S; Kim, K G; Kim, J H; Yu, H G

2011-06-01

To determine whether horizontal macular contraction caused by epiretinal membranes (ERMs) improves after surgical removal. In this prospective, single-center, observational study, 63 consecutive patients with unilateral idiopathic ERM in one eye and no retinal disease in the fellow eye underwent pars plana vitrectomy. Fundus photography and optical coherence tomography (OCT) were performed preoperatively and at 3 months postoperatively. The area enclosed by superior and inferior major vessels from the optic disc to the fovea (area under major vessel (AUV)) and the macroscopic diverging angle (MDA) between superior and inferior major vessels were calculated using digital image analysis of fundus photographs and compared pre- and postoperatively. AUV was significantly smaller in the eyes with ERM compared with the normal fellow eyes (P<0.001). Significant postoperative change in AUV and MDA was demonstrated after ERM removal (P<0.001). However, postoperative AUV of grade 2 and 3 ERM eyes was still significantly smaller than that of normal fellow eyes. Macular thickness differences measured with stratus OCT were positively correlated with AUV differences. Retinal topographic changes caused by ERM improved in part after ERM removal. The improvement of topographic changes were correlated with tomographic changes detected with OCT.

Electro-oculography of smooth pursuit and optokinetic nystagmus eye movements in type I Duane's retraction syndrome.

PubMed

Melek, Nélida B; Blanco, Susana; Garcia, Horacio

2006-01-01

These two eye movements have not been previously studied in this condition by this method. Five cases were studied. Both visual acuity and eye examination of anterior and posterior segments were normal. A Nicolet Nystar Plus system with chloride silver electrodes was used to record the EOG. Of the two systems under study, the smooth pursuit system showed the most relevant anomalies, both in the Duane's eye and in the apparently healthy eye. No correlation was found between the pursuit and optokinetic nystagmus disorders. In some cases, more significant abnormalities were observed in the clinically normal eye. The results clearly demonstrated a significant impairment of the pursuit system. This suggests that this motor disorder is not exclusively caused by hypoplasia or aplasia of the nucleus of the abducens nerve (VIth cranial nerve). These abnormalities might be related to a poor development of the rhombencephalon since both supramotor nuclei as well as the pathways of this system arise from this region of the embryonic brain. In the particular case of OKN, the supramotor nuclei have a different origin. Therefore, these systems might be affected differently.

Number of blastocysts biopsied as a predictive indicator to obtain at least one normal/balanced embryo following preimplantation genetic diagnosis with single nucleotide polymorphism microarray in translocation cases.

PubMed

Wang, Yi-Zi; Ding, Chen-Hui; Wang, Jing; Zeng, Yan-Hong; Zhou, Wen; Li, Rong; Zhou, Can-Quan; Deng, Ming-Fen; Xu, Yan-Wen

2017-01-01

The aim of this study is to investigate the minimum number of blastocysts for biopsy to increase the likelihood of obtaining at least one normal/balanced embryo in preimplantation genetic diagnosis (PGD) for translocation carriers. This blinded retrospective study included 55 PGD cycles for Robertsonian translocation (RT) and 181 cycles for reciprocal translocation (rcp) to indicate when only one of the couples carried a translocation. Single-nucleotide polymorphism microarray after trophectoderm biopsy was performed. Reliable results were obtained for 355/379 (93.7 %) biopsied blastocysts in RT group and 986/1053 (93.6 %) in rcp group. Mean numbers of biopsied embryos per patient, normal/balanced embryos per patient, and mean normal/balanced embryo rate per patient were 7.4, 3.1, and 40.7 % in RT group and 8.0, 2.1, and 27.3 %, respectively, in rcp group. In a regression model, three factors significantly affected the number of genetically transferrable embryos: number of biopsied embryos (P = 0.001), basal FSH level (P = 0.040), and maternal age (P = 0.027). ROC analysis with a cutoff of 1.5 was calculated for the number of biopsied embryos required to obtain at least one normal/balanced embryo for RT carriers. For rcp carriers, the cutoff was 3.5. The clinical pregnancy rate per embryo transfer was 44.2 and 42.6 % in RT and rcp groups (P = 0.836). The minimum numbers of blastocysts to obtain at least one normal/balanced embryo for RT and rcp were 2 and 4 under the conditions of female age < 37 years with a basal FSH level < 11.4 IU/L.

Deconstructing Interocular Suppression: Attention and Divisive Normalization

PubMed Central

Li, Hsin-Hung; Carrasco, Marisa; Heeger, David J.

2015-01-01

In interocular suppression, a suprathreshold monocular target can be rendered invisible by a salient competitor stimulus presented in the other eye. Despite decades of research on interocular suppression and related phenomena (e.g., binocular rivalry, flash suppression, continuous flash suppression), the neural processing underlying interocular suppression is still unknown. We developed and tested a computational model of interocular suppression. The model included two processes that contributed to the strength of interocular suppression: divisive normalization and attentional modulation. According to the model, the salient competitor induced a stimulus-driven attentional modulation selective for the location and orientation of the competitor, thereby increasing the gain of neural responses to the competitor and reducing the gain of neural responses to the target. Additional suppression was induced by divisive normalization in the model, similar to other forms of visual masking. To test the model, we conducted psychophysics experiments in which both the size and the eye-of-origin of the competitor were manipulated. For small and medium competitors, behavioral performance was consonant with a change in the response gain of neurons that responded to the target. But large competitors induced a contrast-gain change, even when the competitor was split between the two eyes. The model correctly predicted these results and outperformed an alternative model in which the attentional modulation was eye specific. We conclude that both stimulus-driven attention (selective for location and feature) and divisive normalization contribute to interocular suppression. PMID:26517321

Constant light affects retinal dopamine levels and blocks deprivation myopia but not lens-induced refractive errors in chickens.

PubMed

Bartmann, M; Schaeffel, F; Hagel, G; Zrenner, E

1994-01-01

Chickens were raised with either translucent occluders or lenses, both under normal light cycles (12-h light/12-h dark) and in constant light (CL). Under normal light cycles, eyes with occluders became very myopic, and eyes with lenses became either relatively hyperopic (positive lenses) or myopic (negative lenses). After the treatment, retinal dopamine (DA), DOPAC, and serotonin levels were measured by high-pressure liquid chromatography (HPLC-EC). A significant drop in daytime retinal DOPAC (-20%) was observed after 1 week of deprivation, and in both DOPAC (-40%) and DA (-30%) after 2 weeks of deprivation. No changes in retinal serotonin levels were found. Retinal DA or DOPAC content remained unchanged after 2 or 4 days of lens wearing even though the lenses had already exerted their maximal effect on axial eye growth. When the chickens were raised in CL, development of deprivation myopia was reduced (8 days CL) or entirely blocked (13 days CL). Lens-induced changes in eye growth were not different after either 6 or 11 days in CL, compared to animals raised in a normal light cycle. Thirteen days of CL resulted in a dramatic reduction of DA and DOPAC levels, but serotonin levels were also lowered. The results suggest that lens-induced changes in refraction may not be dependent on dopaminergic pathways whereas deprivation myopia requires normal diurnal DA rhythms to develop.

Pilot Study of Optical Coherence Tomography Measurement of Retinal Blood Flow in Retinal and Optic Nerve Diseases

PubMed Central

Wang, Yimin; Fawzi, Amani A.; Varma, Rohit; Sadun, Alfredo A.; Zhang, Xinbo; Tan, Ou; Izatt, Joseph A.

2011-01-01

Purpose. To investigate blood flow changes in retinal and optic nerve diseases with Doppler Fourier domain optical coherence tomography (OCT). Methods. Sixty-two participants were divided into five groups: normal, glaucoma, nonarteritic ischemic optic neuropathy (NAION), treated proliferative diabetic retinopathy (PDR), and branch retinal vein occlusion (BRVO). Doppler OCT was used to scan concentric circles of 3.4- and 3.75-mm diameters around the optic nerve head. Flow in retinal veins was calculated from the OCT velocity profiles. Arterial and venous diameters were measured from OCT Doppler and reflectance images. Results. Total retinal blood flow in normal subjects averaged 47.6 μL/min. The coefficient of variation of repeated measurements was 11% in normal eyes and 14% in diseased eyes. Eyes with glaucoma, NAION, treated PDR, and BRVO had significantly decreased retinal blood flow compared with normal eyes (P < 0.001). In glaucoma patients, the decrease in blood flow was highly correlated with the severity of visual field loss (P = 0.003). In NAION and BRVO patients, the hemisphere with more severe disease also had lower blood flow. Conclusions. Doppler OCT retinal blood flow measurements showed good repeatability and excellent correlation with visual field and clinical presentations. This approach could enhance our understanding of retinal and optic nerve diseases and facilitate the development of new therapies. PMID:21051715

Deconstructing Interocular Suppression: Attention and Divisive Normalization.

PubMed

Li, Hsin-Hung; Carrasco, Marisa; Heeger, David J

2015-10-01

In interocular suppression, a suprathreshold monocular target can be rendered invisible by a salient competitor stimulus presented in the other eye. Despite decades of research on interocular suppression and related phenomena (e.g., binocular rivalry, flash suppression, continuous flash suppression), the neural processing underlying interocular suppression is still unknown. We developed and tested a computational model of interocular suppression. The model included two processes that contributed to the strength of interocular suppression: divisive normalization and attentional modulation. According to the model, the salient competitor induced a stimulus-driven attentional modulation selective for the location and orientation of the competitor, thereby increasing the gain of neural responses to the competitor and reducing the gain of neural responses to the target. Additional suppression was induced by divisive normalization in the model, similar to other forms of visual masking. To test the model, we conducted psychophysics experiments in which both the size and the eye-of-origin of the competitor were manipulated. For small and medium competitors, behavioral performance was consonant with a change in the response gain of neurons that responded to the target. But large competitors induced a contrast-gain change, even when the competitor was split between the two eyes. The model correctly predicted these results and outperformed an alternative model in which the attentional modulation was eye specific. We conclude that both stimulus-driven attention (selective for location and feature) and divisive normalization contribute to interocular suppression.

Recognizing patterns of visual field loss using unsupervised machine learning

NASA Astrophysics Data System (ADS)

Yousefi, Siamak; Goldbaum, Michael H.; Zangwill, Linda M.; Medeiros, Felipe A.; Bowd, Christopher

2014-03-01

Glaucoma is a potentially blinding optic neuropathy that results in a decrease in visual sensitivity. Visual field abnormalities (decreased visual sensitivity on psychophysical tests) are the primary means of glaucoma diagnosis. One form of visual field testing is Frequency Doubling Technology (FDT) that tests sensitivity at 52 points within the visual field. Like other psychophysical tests used in clinical practice, FDT results yield specific patterns of defect indicative of the disease. We used Gaussian Mixture Model with Expectation Maximization (GEM), (EM is used to estimate the model parameters) to automatically separate FDT data into clusters of normal and abnormal eyes. Principal component analysis (PCA) was used to decompose each cluster into different axes (patterns). FDT measurements were obtained from 1,190 eyes with normal FDT results and 786 eyes with abnormal (i.e., glaucomatous) FDT results, recruited from a university-based, longitudinal, multi-center, clinical study on glaucoma. The GEM input was the 52-point FDT threshold sensitivities for all eyes. The optimal GEM model separated the FDT fields into 3 clusters. Cluster 1 contained 94% normal fields (94% specificity) and clusters 2 and 3 combined, contained 77% abnormal fields (77% sensitivity). For clusters 1, 2 and 3 the optimal number of PCA-identified axes were 2, 2 and 5, respectively. GEM with PCA successfully separated FDT fields from healthy and glaucoma eyes and identified familiar glaucomatous patterns of loss.

Determination of corneal elasticity coefficient using the ORA database.

PubMed

Avetisov, Sergei E; Novikov, Ivan A; Bubnova, Irina A; Antonov, Alexei A; Siplivyi, Vladimir I

2010-07-01

To propose a new approach for the study of corneal biomechanics using the Reichert Ocular Response Analyzer (ORA) database, which is based on changes in velocity retardation in the central cornea at the peak of flattening. The ORA applanation curve was analyzed using a mathematical technique, which allowed calculation of the elasticity coefficient (Ke), which is primarily characteristic of the elastic properties of the cornea. Elasticity coefficient values were obtained in patients with presumably different biomechanical properties of the cornea: "normal" cornea (71 eyes, normal group), keratoconus (34 eyes, keratoconus group), LASIK (36 eyes, LASIK group), and glaucoma with elevated and compensated intraocular pressure (lOP) (38 eyes, glaucoma group). The mean Ke value in the normal group was 11.05 +/- 1.6, and the corneal thickness correlation coefficient r2 was 0.48. In the keratoconus group, the mean Ke value was 4.91 +/- 1.87 and the corneal thickness correlation coefficient r2 was 0.47. In the LASIK group, Ke and r2 were 5.99 +/- 1.18 and 0.39, respectively. In the glaucoma group, the same eyes that experienced a two-fold reduction in lOP developed a statistically significant reduction in the Ke (1.06 times lower), whereas their corneal hysteresis value increased 1.25 times. The elasticity coefficient calculated using the ORA applanation curve can be used in the evaluation of corneal biomechanical properties.

Analysis of tear cytokines and clinical correlations in Sjögren syndrome dry eye patients and non-Sjögren syndrome dry eye patients.

PubMed

Lee, Sang Yeop; Han, Soo Jung; Nam, Sang Min; Yoon, Sang Chul; Ahn, Ji Min; Kim, Tae-Im; Kim, Eung Kweon; Seo, Kyoung Yul

2013-08-01

To compare concentrations of tear cytokines in 3 groups composed of Sjögren syndrome (SS) dry eye, non-Sjögren syndrome (non-SS) dry eye, and normal subjects. Correlations between ocular surface parameters and tear cytokines were also investigated. Prospective cross-sectional study. SS dry eye patients (n = 24; 40 eyes) were diagnosed with primary SS according to the criteria set by the American-European Consensus Group. Non-SS dry eye patients (n = 25; 40 eyes) and normal subjects (n = 21; 35 eyes) were also enrolled. Tear concentrations of interleukin (IL)-17, IL-6, IL-10, IL-4, IL-2, interferon γ (IFN-γ), and tumor necrosis factor α (TNF-α) were measured by a multiplex immunobead assay. Ocular Surface Disease Index (OSDI), tear film breakup time (TBUT), Schirmer I test, and fluorescein staining scores were obtained from dry eye patients. All cytokine levels except for IL-2 were highest in the SS group, followed by non-SS dry eye group and control subjects. Concentrations of IL-17, TNF-α, and IL-6 were significantly different among the 3 groups (IL-17: SS > control P < .001, non-SS > control P = .042, SS > non-SS P < .001; TNF-α: SS > control P = .006, non-SS > control P = .034, SS > non-SS P = .029; IL-6: SS > control P = .002, non-SS > control P = .032, SS > non-SS P = .002). IL-17 was significantly correlated with TBUT (R = -0.22, P = .012) and Schirmer I test (R = -0.36, P = .027) scores in the SS group. IL-6 was significantly correlated only with TBUT (R = -0.38, P = .02) in the non-SS group. Differences in tear cytokine levels and correlation patterns between SS dry eye and non-SS dry eye patients suggest the involvement of different inflammatory processes as causes of dry eye syndrome. Copyright © 2013 Elsevier Inc. All rights reserved.

Binocular combination in abnormal binocular vision

PubMed Central

Ding, Jian; Klein, Stanley A.; Levi, Dennis M.

2013-01-01

We investigated suprathreshold binocular combination in humans with abnormal binocular visual experience early in life. In the first experiment we presented the two eyes with equal but opposite phase shifted sine waves and measured the perceived phase of the cyclopean sine wave. Normal observers have balanced vision between the two eyes when the two eyes' images have equal contrast (i.e., both eyes contribute equally to the perceived image and perceived phase = 0°). However, in observers with strabismus and/or amblyopia, balanced vision requires a higher contrast image in the nondominant eye (NDE) than the dominant eye (DE). This asymmetry between the two eyes is larger than predicted from the contrast sensitivities or monocular perceived contrast of the two eyes and is dependent on contrast and spatial frequency: more asymmetric with higher contrast and/or spatial frequency. Our results also revealed a surprising NDE-to-DE enhancement in some of our abnormal observers. This enhancement is not evident in normal vision because it is normally masked by interocular suppression. However, in these abnormal observers the NDE-to-DE suppression was weak or absent. In the second experiment, we used the identical stimuli to measure the perceived contrast of a cyclopean grating by matching the binocular combined contrast to a standard contrast presented to the DE. These measures provide strong constraints for model fitting. We found asymmetric interocular interactions in binocular contrast perception, which was dependent on both contrast and spatial frequency in the same way as in phase perception. By introducing asymmetric parameters to the modified Ding-Sperling model including interocular contrast gain enhancement, we succeeded in accounting for both binocular combined phase and contrast simultaneously. Adding binocular contrast gain control to the modified Ding-Sperling model enabled us to predict the results of dichoptic and binocular contrast discrimination experiments and provides new insights into the mechanisms of abnormal binocular vision. PMID:23397039

Binocular combination in abnormal binocular vision.

PubMed

Ding, Jian; Klein, Stanley A; Levi, Dennis M

2013-02-08

We investigated suprathreshold binocular combination in humans with abnormal binocular visual experience early in life. In the first experiment we presented the two eyes with equal but opposite phase shifted sine waves and measured the perceived phase of the cyclopean sine wave. Normal observers have balanced vision between the two eyes when the two eyes' images have equal contrast (i.e., both eyes contribute equally to the perceived image and perceived phase = 0°). However, in observers with strabismus and/or amblyopia, balanced vision requires a higher contrast image in the nondominant eye (NDE) than the dominant eye (DE). This asymmetry between the two eyes is larger than predicted from the contrast sensitivities or monocular perceived contrast of the two eyes and is dependent on contrast and spatial frequency: more asymmetric with higher contrast and/or spatial frequency. Our results also revealed a surprising NDE-to-DE enhancement in some of our abnormal observers. This enhancement is not evident in normal vision because it is normally masked by interocular suppression. However, in these abnormal observers the NDE-to-DE suppression was weak or absent. In the second experiment, we used the identical stimuli to measure the perceived contrast of a cyclopean grating by matching the binocular combined contrast to a standard contrast presented to the DE. These measures provide strong constraints for model fitting. We found asymmetric interocular interactions in binocular contrast perception, which was dependent on both contrast and spatial frequency in the same way as in phase perception. By introducing asymmetric parameters to the modified Ding-Sperling model including interocular contrast gain enhancement, we succeeded in accounting for both binocular combined phase and contrast simultaneously. Adding binocular contrast gain control to the modified Ding-Sperling model enabled us to predict the results of dichoptic and binocular contrast discrimination experiments and provides new insights into the mechanisms of abnormal binocular vision.

Ischemic and Nephrotoxic Acute Renal Failure are Distinguished by their Broad Transcriptomic Responses (102/160 char)

PubMed Central

Yuen, Peter S.T.; Jo, Sang-Kyung; Holly, Mikaela K.; Hu, Xuzhen; Star, Robert A.

2006-01-01

Acute renal failure (ARF) has a high morbidity and mortality. In animal ARF models, effective treatments must be administered before or shortly after the insult, limiting their clinical potential. We used microarrays to identify early biomarkers that distinguish ischemic from nephrotoxic ARF, or biomarkers that detect both injury types. We compared rat kidney transcriptomes 2 and 8 hours after ischemia/reperfusion and after mercuric chloride. Quality control and statistical analyses were necessary to normalize microarrays from different lots, eliminate outliers, and exclude unaltered genes. Principal component analysis revealed distinct ischemic and nephrotoxic trajectories, and clear array groupings. Therefore, we used supervised analysis, t-tests and fold changes, to compile gene lists for each group, exclusive or non-exclusive, alone or in combination. There was little network connectivity, even in the largest group. Some microarray-identified genes were validated by TaqMan assay, ruling out artifacts. Western blotting confirmed that HO-1 and ATF3 proteins were upregulated; however, unexpectedly, their localization changed within the kidney. HO-1 staining shifted from cortical (early) to outer stripe of the outer medulla (late), primarily in detaching cells, after mercuric chloride, but not ischemia/reperfusion. ATF3 staining was similar, but with additional early transient expression in the outer stripe after ischemia/reperfusion. We conclude that microarray-identified genes must be evaluated not only for protein levels, but also for anatomical distribution among different zones, nephron segments, or cell types. Although protein detection reagents are limited, microarray data lay a rich foundation to explore biomarkers, therapeutics, and pathophysiology of ARF. PMID:16507785

Analysis and modelling of septic shock microarray data using Singular Value Decomposition.

PubMed

Allanki, Srinivas; Dixit, Madhulika; Thangaraj, Paul; Sinha, Nandan Kumar

2017-06-01

Being a high throughput technique, enormous amounts of microarray data has been generated and there arises a need for more efficient techniques of analysis, in terms of speed and accuracy. Finding the differentially expressed genes based on just fold change and p-value might not extract all the vital biological signals that occur at a lower gene expression level. Besides this, numerous mathematical models have been generated to predict the clinical outcome from microarray data, while very few, if not none, aim at predicting the vital genes that are important in a disease progression. Such models help a basic researcher narrow down and concentrate on a promising set of genes which leads to the discovery of gene-based therapies. In this article, as a first objective, we have used the lesser known and used Singular Value Decomposition (SVD) technique to build a microarray data analysis tool that works with gene expression patterns and intrinsic structure of the data in an unsupervised manner. We have re-analysed a microarray data over the clinical course of Septic shock from Cazalis et al. (2014) and have shown that our proposed analysis provides additional information compared to the conventional method. As a second objective, we developed a novel mathematical model that predicts a set of vital genes in the disease progression that works by generating samples in the continuum between health and disease, using a simple normal-distribution-based random number generator. We also verify that most of the predicted genes are indeed related to septic shock. Copyright © 2017 Elsevier Inc. All rights reserved.

Foveal shape and structure in a normal population.

PubMed

Tick, Sarah; Rossant, Florence; Ghorbel, Itebeddine; Gaudric, Alain; Sahel, José-Alain; Chaumet-Riffaud, Philippe; Paques, Michel

2011-07-29

The shape of the human fovea presents important but still poorly characterized variations. In this study, the variability of the shape and structure of normal foveae were examined. In a group of 110 eyes of 57 healthy adults, the shape and structure of the fovea were analyzed by automated segmentation of retinal layer on high-resolution optical coherence tomography scans. In an additional group of 10 normal eyes of 10 patients undergoing fluorescein angiography, the size of the foveal avascular zone (FAZ) was correlated to foveal shape. From the thickest to the thinnest fovea, there was a structural continuum ranging from a shallow pit with continuity of the inner nuclear layer (INL) over the center (seven eyes; 6.7%), to a complete separation of inner layers overlying a flat and thinner central outer nuclear layer (ONL; eight eyes; 7.3%). Central foveal thickness correlated inversely to the degree of inner layer separation and to the surface of the FAZ. Foveal structure strongly correlates with its neurovascular organization. The findings support a developmental model in which the size of the FAZ determines the extent of centrifugal migration of inner retinal layers, which counteracts in some way the centripetal packing of cone photoreceptors.

Dry eye, sleep quality, and mood status in glaucoma patients receiving prostaglandin monotherapy were comparable with those in non-glaucoma subjects.

PubMed

Ra, Shugyoku; Ayaki, Masahiko; Yuki, Kenya; Tsubota, Kazuo; Negishi, Kazuno

2017-01-01

Prior studies suggested that glaucoma patients suffer worse dry eye and mood and sleep disorders than non-glaucoma subjects. Prostaglandin analogues are first-line therapy for glaucoma, inducing few instillation problems and sufficient pressure-reduction effects. This study compared dry eye, sleep quality, and mood status between glaucoma patients receiving prostaglandin monotherapy and non-glaucoma subjects. This cross-sectional study evaluated 1520 patients (579 males and 941 females) for glaucoma status and dry eye-related symptoms (dryness, eye fatigue, photophobia, pain, blurring) and signs (Schirmer test, tear break-up time, corneal staining scores). Of the total cohort, 93 patients were also evaluated by Pittsburgh sleep quality index (PSQI) and hospital anxiety and depression score (HADS). Inclusion criteria were consecutive patients ≥ 51 years of age and best-corrected visual acuity ≥ 20/25. Glaucoma patients included those treated with prostaglandin or a fixed combination including prostaglandin. Exclusion criteria were history of ocular surgery within one month. Data were analyzed using the chi-square or Mann-Whitney U tests, at 5% significance. There were no significant differences in dry eye-related signs and symptoms between the control (n = 1431, mean age of 66.9 years) and glaucoma groups (n = 89, 67.9 years). The psychiatric sub-analysis of the control (n = 61, 66.2 years) and glaucoma groups (n = 32, 67.3 years) revealed mean scores of 5.02 ± 3.10 and 5.16 ± 3.46 for PSQI (normal range ≤ 5), 9.47 ± 5.61 and 9.42 ± 7.36 for HADS (normal range ≤ 10), 4.84 ± 3.22 and 4.71 ± 3.45 for anxiety (normal range ≤ 5), and 4.63 ± 3.05 and 4.71 ± 4.40 for depression (normal range ≤ 5), respectively, without statistical significance. Our results were comparable between glaucoma patients on prostaglandin monotherapy and non-glaucoma subjects for dry eye-related clinical manifestations, sleep quality, and mood status.

An uncommon case of intermittent Pourfour du Petit Syndrome associated with acute angle-closure glaucoma successfully treated by laser iridotomy.

PubMed

Farci, Roberta; Napoli, Pietro Emanuele; Fossarello, Maurizio

2017-07-03

To describe a case of acute angle-closure glaucoma secondary to intermittent mydriasis related to Pourfour du Petit Syndrome caused by tracheal deviation. A 70-year-old Caucasian woman visited the Emergency Room of the University Eye Clinic complaining of blurring of vision and difficulty to move superior eyelid in her right eye. Examination revealed reactive mydriasis, and upper lid retraction on the right side. The rest of the ophthalmological examination was normal, and a cranial computed tomography (CT) did not identify any abnormalities. A cervical CT showed the presence of an accentuated lateral right convex deviation of the trachea, attributable to a fibrothorax. A right Pourfour du Petit syndrome was suspected. Although the mydriasis had in the meantime vanished, the patient was admitted to the Neurological Clinic. Five days later she suffered acute pain in her right eye. Ophthalmological examination of the right eye revealed conjunctival hyperemia, marked corneal edema, reduced depth of anterior chamber, permanent mydriasis. As assessed by Goldmann applanation tonometry, intraocular pressure (IOP) was 48 mm Hg. Fundus examination was normal in both eyes. Gonioscopy revealed angle closure in all quadrants. Slit lamp examination of the contralateral eye was normal; IOP was 10 mm Hg. After hypotensive medical therapy, iridotomy with YAG laser was performed. Thereafter, IOP stabilized at 12 mm Hg. This is the first report in the literature of a case of acute angle-closure glaucoma secondary to mydriasis related to Pourfour du Petit Syndrome caused by tracheal deviation.

The Influence of Very Low Illumination on the Postural Sway of Young and Elderly Adults

PubMed Central

Rugelj, Darja; Gomišček, Gregor; Sevšek, France

2014-01-01

The purpose of the present study was to evaluate the influence of very low ambient illumination and complete darkness on the postural sway of young and elderly adults. Eighteen healthy young participants aged 23.8±1.5 years and 26 community-dwelling elderly aged 69.8±5.6 years were studied. Each participant performed four tests while standing on a force platform in the following conditions: in normal light (215 lx) with open eyes and with closed eyes, in very low illumination (0.25 lx) with open eyes, and in complete darkness with open eyes. The sequences of the tests in the altered visual conditions were determined by random blocs. Postural sway was assessed by means of the force platform measurements. The centre of pressure variables: the medio-lateral and antero-posterior path lengths, mean velocities, sway areas, and fractal dimensions were analysed. Very low illumination resulted in a statistically significant increase in postural sway in both the young and elderly groups compared to normal light, although the increase was significantly smaller than those observed in the eyes closed and complete darkness condition, and no significant effects of illumination on fractal dimensions were detected. The gains of the sways in the very low or no illumination conditions relative to the normal light condition were significantly larger in the group of young participants than in the group of elderly participants (up to 50% and 25%, respectively). However, the response patterns to changes in illumination were similar in the young and elderly participants, with the exception of the short-range fractal dimension of the medio-lateral sway. In conclusion, very low illumination resulted in increased postural sway compared to normal illumination; however, in the closed eye and complete darkness conditions, postural sway was significantly higher than in the very low illumination condition regardless of the age of the participants. PMID:25084015

Improving Viability and Functional Outcome After Whole Eye Transplantation

DTIC Science & Technology

2015-10-01

preservation of the structural layers of the retina, and blood flow throughout the eye. Intraocular pressure in the transplanted eyes was within normal...imaging was performed to assess blood flow in the eye. Doppler OCT was performed in a 2.5mm x 2.5mm x 2mm (700 x 20 x 1024 samplings) region. Eight...layers was maintained. (Fig. 4) There was thinning of the retina, especially the anterior hyperreflective layer. Blood flow was observed in the retina

iSyTE 2.0: a database for expression-based gene discovery in the eye

PubMed Central

Kakrana, Atul; Yang, Andrian; Anand, Deepti; Djordjevic, Djordje; Ramachandruni, Deepti; Singh, Abhyudai; Huang, Hongzhan

2018-01-01

Abstract Although successful in identifying new cataract-linked genes, the previous version of the database iSyTE (integrated Systems Tool for Eye gene discovery) was based on expression information on just three mouse lens stages and was functionally limited to visualization by only UCSC-Genome Browser tracks. To increase its efficacy, here we provide an enhanced iSyTE version 2.0 (URL: http://research.bioinformatics.udel.edu/iSyTE) based on well-curated, comprehensive genome-level lens expression data as a one-stop portal for the effective visualization and analysis of candidate genes in lens development and disease. iSyTE 2.0 includes all publicly available lens Affymetrix and Illumina microarray datasets representing a broad range of embryonic and postnatal stages from wild-type and specific gene-perturbation mouse mutants with eye defects. Further, we developed a new user-friendly web interface for direct access and cogent visualization of the curated expression data, which supports convenient searches and a range of downstream analyses. The utility of these new iSyTE 2.0 features is illustrated through examples of established genes associated with lens development and pathobiology, which serve as tutorials for its application by the end-user. iSyTE 2.0 will facilitate the prioritization of eye development and disease-linked candidate genes in studies involving transcriptomics or next-generation sequencing data, linkage analysis and GWAS approaches. PMID:29036527

Corneal permeability changes in dry eye disease: an observational study.

PubMed

Fujitani, Kenji; Gadaria, Neha; Lee, Kyu-In; Barry, Brendan; Asbell, Penny

2016-05-13

Diagnostic tests for dry eye disease (DED), including ocular surface disease index (OSDI), tear breakup time (TBUT), corneal fluorescein staining, and lissamine staining, have great deal of variability. We investigated whether fluorophotometry correlated with previously established DED diagnostic tests and whether it could serve as a novel objective metric to evaluate DED. Dry eye patients who have had established signs or symptoms for at least 6 months were included in this observational study. Normal subjects with no symptoms of dry eyes served as controls. Each eye had a baseline fluorescein scan prior to any fluorescein dye. Fluorescein dye was then placed into both eyes, rinsed with saline solution, and scanned at 5, 10, 15, and 30 min. Patients were administered the following diagnostic tests to correlate with fluorophotometry: OSDI, TBUT, fluorescein, and lissamine. Standard protocols were used. P < 0.05 was considered significant. Fifty eyes from 25 patients (DED = 22 eyes, 11 patients; Normal = 28 eyes, 14 patients) were included. Baseline scans of the dry eye and control groups did not show any statistical difference (p = 0.84). Fluorescein concentration of DED and normal patients showed statistical significance at all time intervals (p < 10(-5), 0.001, 0.002, 0.049 for 5, 10, 15, & 30 min respectively). Fluorophotometry values converged towards baseline as time elapsed, but both groups were still statistically different at 30 min (p < 0.01). We used four fluorophotometry scoring methods and correlated them with OSDI, TBUT, fluorescein, and lissamine along with adjusted and aggregate scores. The four scoring schemes did not show any significant correlations with the other tests, except for correlations seen with lissamine and 10 (p = 0.045, 0.034) and 15 min (p = 0.013, 0.012), and with aggregate scores and 15 min (p = 0.042, 0.017). Fluorophotometry generally did not correlate with any other DED tests, even though it showed capability of differentiating between DED and normal eyes up to 30 min after fluorescein dye instillation. There may be an aspect of DED that is missed in the current regimen of DED tests and only captured with fluorophotometry. Adding fluorophotometry may be useful in screening, diagnosing, and monitoring patients with DED.

Computer Analysis of Eye Blood-Vessel Images

NASA Technical Reports Server (NTRS)

Wall, R. J.; White, B. S.

1984-01-01

Technique rapidly diagnoses diabetes mellitus. Photographs of "whites" of patients' eyes scanned by computerized image analyzer programmed to quantify density of small blood vessels in conjuctiva. Comparison with data base of known normal and diabetic patients facilitates rapid diagnosis.

Evaluation of optic nerve head blood flow in normal rats and a rodent model of non-arteritic ischemic optic neuropathy using laser speckle flowgraphy.

PubMed

Takako, Hidaka; Hideki, Chuman; Nobuhisa, Nao-I

2017-10-01

To evaluate optic nerve head (ONH) blood flow in normal rats and a rodent model of non-arteritic ischemic optic neuropathy (rNAION) in vivo using laser speckle flowgraphy (LSFG). Rats were under general anesthesia; to induce NAION, Rose Bengal (RB) was injected into the tail vein. After the administration of RB, the left ONH was photoactivated using an argon green laser. We measured ONH blood flow in the normal rats and the rNAION group (at 1, 3, 7, 14, and 28 days after the induction of NAION) using an LSFG-Micro. We used the mean blur rate (MBR) of the vessel region (MV) and MBR of the tissue region (MT) as indicators of blood flow. We compared the MBR of the right and left eyes in both the normal rats and the rNAION group. In the normal rats, there were no significant differences in MV or MT between the right and left eyes. In the rNAION group, the MV and MT of the affected eyes were significantly lower than those of the unaffected eyes at all time points. There were significant differences between the left/right MV and MT ratios seen before the induction of NAION and those observed at 1, 3, 7, 14, and 28 days after the induction of NAION. However, there were no significant differences in these parameters among any of post-NAION induction time points. Our results indicated that the ONH blood flow of the rNAION rats fell in the acute and chronic phases.

Scanning Laser Polarimetry with Variable and Enhanced Corneal Compensation in Normal and Glaucomatous Eyes

PubMed Central

Sehi, Mitra; Guaqueta, Delia C.; Feuer, William J.; Greenfield, David S.

2007-01-01

Purpose To investigate whether correction for atypical birefringence pattern (ABP) using scanning laser polarimetry with enhanced corneal compensation (SLP-ECC) reduces the severity of ABP compared with variable corneal compensation (SLP-VCC), and improves the correlation with visual function. Design Prospective observational study. Methods Normal and glaucomatous eyes enrolled from 4 clinical sites underwent complete examination, automated perimetry, SLP-ECC and SLP-VCC. Eyes were characterized in 3 groups based upon the typical scan score (TSS): normal birefringence pattern (NBP) was defined as TSS 80, mild ABP as TSS 61–79, moderate-severe ABP as TSS 60. For each of 4 SLP parameters the area under the ROC curve (AUROC) was calculated to compare the ability of SLP-ECC and SLP-VCC to discriminate between normal and glaucomatous eyes. Results Eighty-four normal volunteers and 45 glaucoma patients were enrolled. Mean TSS was significantly (p<0.001) greater using SLP-ECC (98.0 ± 6.6) compared to SLP-VCC (83.4 ± 22.5). The frequency of moderate-severe ABP images was significantly (p<0.001, McNemar test) higher using SLP-VCC (18 of 129, 14%) compared to SLP-ECC (1 of 129, 0.8%). Two SLP-ECC parameters (TSNIT average and inferior average) had significantly (p=0.01, p<0.001) higher correlation (r=0.45, r=0.50 respectively) with MD compared to SLP-VCC (r=0.34, r=0.37). Among eyes with moderate-severe ABP (N = 18), inferior average obtained using SLP-ECC had significantly (p=0.03) greater AUROC (0.91 ± 0.07) compared with SLP-VCC (0.78 ± 0.11). Conclusions SLP-ECC significantly reduces the frequency and severity of ABP compared to SLP-VCC and improves the correlation between RNFL measures and visual function. PMID:17157800

Comparison of iCare tonometer and Goldmann applanation tonometry in normal corneas and in eyes with automated lamellar and penetrating keratoplasty

PubMed Central

Salvetat, M L; Zeppieri, M; Miani, F; Tosoni, C; Parisi, L; Brusini, P

2011-01-01

Purpose To compare intraocular pressure (IOP) measurements with Goldmann applanation tonometry (GAT) and iCare tonometry in normal and post-keratoplasty corneas and to assess the influence of central corneal thickness (CCT), corneal curvature (CC), and corneal astigmatism (CA) on IOP. Methods This prospective cross-sectional study included one eye of 101 subjects with normal corneas (58 healthy subjects, 43 glaucoma); and 90 post-keratoplasty patients: 34 penetrating keratoplasties (PK); 20 automated-lamellar-therapeutic keratoplasties (ALTK); 19 Descemet-stripping-automated-endothelial keratoplasties (DSAEK); 17 edematous grafts. All subjects underwent GAT and iCare IOP measurements in random order, and CCT, CC, and CA evaluation. The Bland–Altman method and multivariate regression analysis were used to assess inter-tonometer agreement and the influence of CCT, CC, and CA on IOP. Results iCare significantly underestimated IOP in all groups compared with GAT (GAT minus iCare of 3.5±3.5 mm Hg, P<0.001), but overestimated IOP in the edematous grafts (GAT minus iCare of −6.5±1.9 mm Hg, P<0.001). In normal corneas, both tonometer measurements were directly related to CCT values; iCare readings appeared inversely related to CC. There was no significant relationship between IOP and CCT, CC and CA in post-keratoplasty eyes, except between CC and iCare measurements for PK eyes. Conclusions The agreement between GAT and iCare was clinically acceptable in control, ALTK and DSAEK groups, and poor in PK and edematous grafts eyes. In normal corneas, GAT was significantly affected by CCT; iCare was influenced by CCT and CC. The iCare appeared less influenced by corneal edema when compared with GAT. High IOP readings taken with both tonometers in grafts should raise suspicion of true elevated IOP. PMID:21436848

A Diagnosis of Insomnia Is Associated With Differential Expression of Sleep-Regulating Genes in Military Personnel.

PubMed

Gill, Jessica M; Lee, Hyunhwa; Baxter, Tristin; Reddy, Swarnalatha Y; Barr, Taura; Kim, Hyung-Suk; Wang, Dan; Mysliwiec, Vincent

2015-07-01

Sleep disturbance is a common and disturbing symptom in military personnel, with many individuals progressing to the development of insomnia, which is characterized by increased arousals, wakefulness after sleep onset, and distorted sleep architecture. The molecular mechanisms underlying insomnia remain elusive, limiting future therapeutic development to address this critical issue. We examined whole gene expression profiles associated with insomnia. We compared subjects with insomnia (n = 25) to controls (n = 13) without insomnia using microarray gene expression profiles obtained from peripheral samples of whole blood obtained from military personnel. Compared to controls, participants with insomnia had differential expression of 44 transcripts from 43 identified genes. Among the identified genes, urotensin 2 was downregulated by more than 6 times in insomnia participants, and the fold-change remained significant after controlling for depression, posttraumatic stress disorder, and medication use. Urotensin 2 is involved in regulation of orexin A and B activity and rapid eye movement during sleep. These findings suggest that differential expression of these sleep-regulating genes contributes to symptoms of insomnia and, specifically, that switching between rapid eye movement and nonrapid eye movement sleep stages underlies insomnia symptoms. Future work to identify therapeutic agents that are able to regulate these pathways may provide novel treatments for insomnia. © The Author(s) 2015.

[Application of chromosomal microarray analysis for the diagnosis of children with intellectual disability/developmental delay and a normal karytype].

PubMed

Hu, Ting; Zhu, Hongmei; Zhang, Zhu; Wang, Jiamin; Liu, Hongqian; Zhang, Xuemei; Zhang, Haixia; Du, Ze; Li, Lingping; Wang, He; Liu, Shanling

2017-04-10

To assess the value of chromosomal microarray analysis (CMA) for the diagnosis of children with intellectual disability/developmental delay (ID/DD) but a normal karytype. Peripheral blood samples from 92 ID/DD patients were analyzed with CMA using Affymetrix CytoScan 750K arrays. The results were analyzed by ChAS v3.0 software. Eighteen cases (19.57%) were detected with abnormalities by CMA, among which 10 cases were diagnosed with microdeletion/microduplication syndromes. These included 2 Williams-Beuren syndromes, 2 Angelman syndromes, 2 Russell-Silver syndromes, 1 Smith-Magenis syndromes, 1 Wolf-Hirschhorn syndromes, 1 15q26 overgrowth syndrome and 1 Xq28 (MECP2) duplication syndrome. In addition, 8 cases were diagnosed with pathogenic copy number variations (pCNV). CMA can significantly improve the diagnostic rate for patients with ID/DD, which is of great value for the treatment of such children and guidance of reproduction for their parents. Therefore, CMA should become the first-line diagnostic test for patients with ID/DD.

Circular RNA hsa_circ_0008344 regulates glioblastoma cell proliferation, migration, invasion, and apoptosis.

PubMed

Zhou, Jinxu; Wang, Hongxiang; Chu, Junsheng; Huang, Qilin; Li, Guangxu; Yan, Yong; Xu, Tao; Chen, Juxiang; Wang, Yuhai

2018-04-24

Recent studies have found circular RNAs (circRNAs) involved in the biological process of cancers. However, little is known about their functional roles in glioblastoma. Human circRNA microarray analysis was performed to screen the expression profile of circRNAs in IDH1 wild-type glioblastoma tissue. The expression of hsa_circ_0008344 in glioblastoma and normal brain samples was quantified by qRT-PCR. Functional experiments were performed to investigate the biological functions of hsa_circ_0008344, including MTT assay, colony formation assay, transwell assay, and cell apoptosis assay. CircRNA microarray revealed a total of 417 abnormally expressed circRNAs (>1.5-fold, P < .05) in glioblastoma tissue compared with the adjacent normal brain. Hsa_circ_0008344, among the top differentially expressed circRNAs, was significantly upregulated in IDH1 wild-type glioblastoma. Further in vitro studies showed that knockdown of hsa_circ_0008344 suppressed glioblastoma cell proliferation, colony formation, migration, and invasion, but increased cell apoptotic rate. Hsa_circ_0008344 is upregulated in glioblastoma and may contribute to the progression of this malignancy. © 2018 Wiley Periodicals, Inc.

Evaluation of a New Software Version of the RTVue Optical Coherence Tomograph for Image Segmentation and Detection of Glaucoma in High Myopia.

PubMed

Holló, Gábor; Shu-Wei, Hsu; Naghizadeh, Farzaneh

2016-06-01

To compare the current (6.3) and a novel software version (6.12) of the RTVue-100 optical coherence tomograph (RTVue-OCT) for ganglion cell complex (GCC) and retinal nerve fiber layer thickness (RNFLT) image segmentation and detection of glaucoma in high myopia. RNFLT and GCC scans were acquired with software version 6.3 of the RTVue-OCT on 51 highly myopic eyes (spherical refractive error ≤-6.0 D) of 51 patients, and were analyzed with both the software versions. Twenty-two eyes were nonglaucomatous, 13 were ocular hypertensive and 16 eyes had glaucoma. No difference was seen for any RNFLT, and average GCC parameter between the software versions (paired t test, P≥0.084). Global loss volume was significantly lower (more normal) with version 6.12 than with version 6.3 (Wilcoxon signed-rank test, P<0.001). The percentage agreement (κ) between the clinical (normal and ocular hypertensive vs. glaucoma) and the software-provided classifications (normal and borderline vs. outside normal limits) were 0.3219 and 0.4442 for average RNFLT, and 0.2926 and 0.4977 for average GCC with versions 1 and 2, respectively (McNemar symmetry test, P≥0.289). No difference in average RNFLT and GCC classification (McNemar symmetry test, P≥0.727) and the number of eyes with at least 1 segmentation error (P≥0.109) was found between the software versions, respectively. Although GCC segmentation was improved with software version 6.12 compared with the current version in highly myopic eyes, this did not result in a significant change of the average RNFLT and GCC values, and did not significantly improve the software-provided classification for glaucoma.

Intra-ocular pressure normalization technique and equipment

NASA Technical Reports Server (NTRS)

Mcgannon, W. J. (Inventor)

1980-01-01

A method and apparatus for safely reducing abnormally high intraocular pressure in an eye during a predetermined time interval is presented. This allows maintenance of normal intraocular pressure during glaucoma surgery. According to the invention, a pressure regulator of the spring biased diaphragm type is provided with additional bias by a column of liquid. The height of the column of liquid is selected such that the pressure at a hypodermic needle connected to the output of the pressure regulator is equal to the measured pressure of the eye. The hypodermic needle can then be safely inserted into the anterior chamber of the eye. Liquid is then bled out of the column to reduce the bias on the diaphragm of the pressure regulator and, consequently, the output pressure of the regulator. This lowering pressure of the regulator also occurs in the eye by means of a small second bleed path provided between the pressure regulator and the hypodermic needle. Alternately, a second hypodermic needle may be inserted into the eye to provide a controlled leak off path for excessive pressure and clouded fluid from the anterior chamber.

Could Buerger's disease cause nonarteritic anterior ischemic optic neuropathy?: a rare case report.

PubMed

Korkmaz, Anil; Karti, Omer; Top Karti, Dilek; Yüksel, Bora; Zengin, Mehmet Ozgur; Kusbeci, Tuncay

2018-04-05

We present an interesting case with nonarteritic anterior ischemic optic neuropathy (NAION) accompanied by Buerger's disease. A 43-year-old man was referred to our neuro-ophthalmology clinic with a complaint of visual deterioration in the left eye that started 5 days ago. He suffered from Buerger's disease, and he had acute pain in the right lower limb below the knee. His best corrected visual acuity was 10/10 in the right eye and 2/10 in the left eye by Snellen chart. There was a relative afferent pupil defect in the left eye. The right optic disc was normal on fundus examination, and blurring, hemorrhagic swelling was found at the left optic disc. Inferior altitudinal visual field defect was observed in the left eye. Neurological examination was normal. Computed tomography angiography scan revealed occlusion in the right posterior tibial artery. Brain imaging and laboratory tests such as blood analyses, genetic screening, coagulation, and lipid panels were unremarkable. NAION may occur in patients with Buerger's disease, but it is extremely rare. Therefore, clinicians should be aware of this rare association.

Hyperspectral microscopic analysis of normal, benign and carcinoma microarray tissue sections

NASA Astrophysics Data System (ADS)

Maggioni, Mauro; Davis, Gustave L.; Warner, Frederick J.; Geshwind, Frank B.; Coppi, Andreas C.; DeVerse, Richard A.; Coifman, Ronald R.

2006-02-01

We apply a unique micro-optoelectromechanical tuned light source and new algorithms to the hyper-spectral microscopic analysis of human colon biopsies. The tuned light prototype (Plain Sight Systems Inc.) transmits any combination of light frequencies, range 440nm 700nm, trans-illuminating H and E stained tissue sections of normal (N), benign adenoma (B) and malignant carcinoma (M) colon biopsies, through a Nikon Biophot microscope. Hyper-spectral photomicrographs, randomly collected 400X magnication, are obtained with a CCD camera (Sensovation) from 59 different patient biopsies (20 N, 19 B, 20 M) mounted as a microarray on a single glass slide. The spectra of each pixel are normalized and analyzed to discriminate among tissue features: gland nuclei, gland cytoplasm and lamina propria/lumens. Spectral features permit the automatic extraction of 3298 nuclei with classification as N, B or M. When nuclei are extracted from each of the 59 biopsies the average classification among N, B and M nuclei is 97.1%; classification of the biopsies, based on the average nuclei classification, is 100%. However, when the nuclei are extracted from a subset of biopsies, and the prediction is made on nuclei in the remaining biopsies, there is a marked decrement in performance to 60% across the 3 classes. Similarly the biopsy classification drops to 54%. In spite of these classification differences, which we believe are due to instrument and biopsy normalization issues, hyper-spectral analysis has the potential to achieve diagnostic efficiency needed for objective microscopic diagnosis.

[Clinical evaluation of the effectiveness of cholinesterase inhibition with neuromidin in the treatment of primary glaucoma patients].

PubMed

Zakharova, I A; Avdeev, R V; Pristavka, V A; Surnin, S N; Makhmutov, V Yu; Savrasova, I I

to investigate neuromidin effectiveness in the treatment of patients with primary glaucoma and compensated intraocular pressure (IOP). A total of 40 patients (80 eyes) were examined. Of them, 10 eyes with early glaucoma, 36 eyes with moderate-stage glaucoma, 33 eyes with advanced glaucoma, and 1 eye with end-stage glaucoma. In 19 eyes, IOP was controlled through beta-blockers, in 11 eyes - through carbonic anhydrase inhibitors, in 10 eyes - through prostaglandin analogues, and in 39 eyes - through combination drugs. Twenty-six eyes had received glaucoma surgery some time earlier. Ipidacrine was prescribed in tablets at 20 mg 2 times daily for 25 days. Treatment effectiveness was judged by visual functions, hydrodynamics, and morphometric parameters of the optic disc. In moderate-stage eyes, visual acuity improved in 66.6% of cases and remained unchanged in 33.3%. In advanced-stage eyes, visual acuity improved in 51.5% of cases and remained unchanged in 48.5%. Visual field broadened in all cases. Moreover, under the neuromidin therapy, the number of scotomas in early-stage eyes decreased, while the number of areas with normal sensitivity of the retina increased by 14.9%. In advanced-stage glaucoma, the effect was less pronounced: the number of type 1 and type 2 scotomas decreased by 3.0±0.6% and 2.9±0.8%, respectively; the number of absolute scotomas did not change; the number of areas with normal sensitivity of the retina increased by 7.4±2.0%. Also, P0 was found to be reduced and intraocular fluid outflow - activated. In early and moderate glaucoma, there was a significant reduction in the cup area as well as an increase in the neuroretinal rim area and retinal nerve fiber layer thickness. In advanced-stage cases, it was only the retinal nerve fiber layer thickness that changed. Neuromidin has a positive impact on visual function, hydrodynamics, and morphometric parameters of the optic disc.

Acute Zonal Cone Photoreceptor Outer Segment Loss

PubMed Central

Sandhu, Harpal S.; Serrano, Leona W.; Traband, Anastasia; Lau, Marisa K.; Adamus, Grazyna; Avery, Robert A.

2017-01-01

Importance The diagnostic path presented narrows down the cause of acute vision loss to the cone photoreceptor outer segment and will refocus the search for the cause of similar currently idiopathic conditions. Objective To describe the structural and functional associations found in a patient with acute zonal occult photoreceptor loss. Design, Setting, and Participants A case report of an adolescent boy with acute visual field loss despite a normal fundus examination performed at a university teaching hospital. Main Outcomes and Measures Results of a complete ophthalmic examination, full-field flash electroretinography (ERG) and multifocal ERG, light-adapted achromatic and 2-color dark-adapted perimetry, and microperimetry. Imaging was performed with spectral-domain optical coherence tomography (SD-OCT), near-infrared (NIR) and short-wavelength (SW) fundus autofluorescence (FAF), and NIR reflectance (REF). Results The patient was evaluated within a week of the onset of a scotoma in the nasal field of his left eye. Visual acuity was 20/20 OU, and color vision was normal in both eyes. Results of the fundus examination and of SW-FAF and NIR-FAF imaging were normal in both eyes, whereas NIR-REF imaging showed a region of hyporeflectance temporal to the fovea that corresponded with a dense relative scotoma noted on light-adapted static perimetry in the left eye. Loss in the photoreceptor outer segment detected by SD-OCT co-localized with an area of dense cone dysfunction detected on light-adapted perimetry and multifocal ERG but with near-normal rod-mediated vision according to results of 2-color dark-adapted perimetry. Full-field flash ERG findings were normal in both eyes. The outer nuclear layer and inner retinal thicknesses were normal. Conclusions and Relevance Localized, isolated cone dysfunction may represent the earliest photoreceptor abnormality or a distinct entity within the acute zonal occult outer retinopathy complex. Acute zonal occult outer retinopathy should be considered in patients with acute vision loss and abnormalities on NIR-REF imaging, especially if multimodal imaging supports an intact retinal pigment epithelium and inner retina but an abnormal photoreceptor outer segment. PMID:28384671

I Can Read It in Your Eyes: What Eye Movements Tell Us about Visuo-Attentional Processes in Developmental Dyslexia

ERIC Educational Resources Information Center

Bellocchi, Stephanie; Muneaux, Mathilde; Bastien-Toniazzo, Mireille; Ducrot, Stephanie

2013-01-01

Most studies today agree about the link between visual-attention and oculomotor control during reading: attention seems to affect saccadic programming, that is, the position where the eyes land in a word. Moreover, recent studies show that visuo-attentional processes are strictly linked to normal and impaired reading. In particular, a large body…

The Long Noncoding RNA Landscape of the Mouse Eye.

PubMed

Chen, Weiwei; Yang, Shuai; Zhou, Zhonglou; Zhao, Xiaoting; Zhong, Jiayun; Reinach, Peter S; Yan, Dongsheng

2017-12-01

Long noncoding RNAs (lncRNAs) are important regulators of diverse biological functions. However, an extensive in-depth analysis of their expression profile and function in mammalian eyes is still lacking. Here we describe comprehensive landscapes of stage-dependent and tissue-specific lncRNA expression in the mouse eye. Affymetrix transcriptome array profiled lncRNA signatures from six different ocular tissue subsets (i.e., cornea, lens, retina, RPE, choroid, and sclera) in newborn and 8-week-old mice. Quantitative RT-PCR analysis validated array findings. Cis analyses and Gene Ontology (GO) annotation of protein-coding genes adjacent to signature lncRNA loci clarified potential lncRNA roles in maintaining tissue identity and regulating eye maturation during the aforementioned phase. In newborn and 8-week-old mice, we identified 47,332 protein-coding and noncoding gene transcripts. LncRNAs comprise 19,313 of these transcripts annotated in public data banks. During this maturation phase of these six different tissue subsets, more than 1000 lncRNAs expression levels underwent ≥2-fold changes. qRT-PCR analysis confirmed part of the gene microarray analysis results. K-means clustering identified 910 lncRNAs in the P0 groups and 686 lncRNAs in the postnatal 8-week-old groups, suggesting distinct tissue-specific lncRNA clusters. GO analysis of protein-coding genes proximal to lncRNA signatures resolved close correlations with their tissue-specific functional maturation between P0 and 8 weeks of age in the 6 tissue subsets. Characterizating maturational changes in lncRNA expression patterns as well as tissue-specific lncRNA signatures in six ocular tissues suggest important contributions made by lncRNA to the control of developmental processes in the mouse eye.

Noonan's Syndrome and Autoimmune Thyroiditis

ERIC Educational Resources Information Center

Vesterhus, Per; Aarskog, Dagfinn

1973-01-01

Thyroid abnormalities were studies in seven boys and three girls, 4- to 17-years-old, with Noonan's syndrome, characterized by mental retardation, ocular anomalies (wide spaced eyes, drooped eye lids, or strabismus), heart lesions, characteristics of Turner's syndrome, and normal karyotypes (chromosome arrangement). (MC)

Concurrent clinical intraocular findings in horses with depigmented punctate chorioretinal foci.

PubMed

Mathes, Rachel L; Burdette, Erin L; Moore, Phillip A; Myrna, Kathern E

2012-03-01

To report concurrent clinical intraocular findings in horses with depigmented punctate chorioretinal foci and to document any correlation with equine recurrent uveitis (ERU). Records of 131 horses (241 eyes) examined at the University of Georgia Veterinary Teaching hospital from 2001 to 2010 were reviewed with either clinically normal fundi or depigmented punctate chorioretinal foci in the absence of other fundic pathology. Data collected included patient signalment, concurrent clinical ocular findings and follow-up information. Sex, presence of no other intraocular findings, presence of ERU, presence of cataracts, and presence of vitreal disease were compared between normal and foci groups using chi-squared analysis. Age and length of follow-up time were compared using a student's t-test. Ninety-one horses (167 eyes) with chorioretinal foci and forty horses (74 eyes) with clinically normal ocular fundi were examined. Fifty-eight (64%) horses with chorioretinal foci and 20 (50%) horses with clinically normal fundi had a normal intraocular examination. There was no significant difference in any of the criteria examined between groups. Horses with depigmented punctate chorioretinal foci, in the absence of other fundic pathology, are not more likely to have intraocular disease or ERU than horses with clinically normal ocular fundi. These findings suggest that depigmented punctate fundic foci in horses are not indicative of or associated with ERU. © 2011 American College of Veterinary Ophthalmologists.

Gaze failure, drifting eye movements, and centripetal nystagmus in cerebellar disease.

PubMed Central

Leech, J; Gresty, M; Hess, K; Rudge, P

1977-01-01

Three abnormalities of eye movement in man are described which are indicative of cerebellar system disorder, namely, centripetally beating nystagmus, failure to maintain lateral gaze either in darkness or with eye closure, and slow drifting movements of the eyes in the absence of fixation. Similar eye movement signs follow cerebellectomy in the primate and the cat. These abnormalities of eye movement, together with other signs of cerebellar disease, such as rebound alternating, and gaze paretic nystagmus, are explained by the hypothesis that the cerebellum helps to maintain lateral gaze and that brain stem mechanisms which monitor gaze position generate compensatory biases in the absence of normal cerebellar function. PMID:603785

ArrayWiki: an enabling technology for sharing public microarray data repositories and meta-analyses

PubMed Central

Stokes, Todd H; Torrance, JT; Li, Henry; Wang, May D

2008-01-01

Background A survey of microarray databases reveals that most of the repository contents and data models are heterogeneous (i.e., data obtained from different chip manufacturers), and that the repositories provide only basic biological keywords linking to PubMed. As a result, it is difficult to find datasets using research context or analysis parameters information beyond a few keywords. For example, to reduce the "curse-of-dimension" problem in microarray analysis, the number of samples is often increased by merging array data from different datasets. Knowing chip data parameters such as pre-processing steps (e.g., normalization, artefact removal, etc), and knowing any previous biological validation of the dataset is essential due to the heterogeneity of the data. However, most of the microarray repositories do not have meta-data information in the first place, and do not have a a mechanism to add or insert this information. Thus, there is a critical need to create "intelligent" microarray repositories that (1) enable update of meta-data with the raw array data, and (2) provide standardized archiving protocols to minimize bias from the raw data sources. Results To address the problems discussed, we have developed a community maintained system called ArrayWiki that unites disparate meta-data of microarray meta-experiments from multiple primary sources with four key features. First, ArrayWiki provides a user-friendly knowledge management interface in addition to a programmable interface using standards developed by Wikipedia. Second, ArrayWiki includes automated quality control processes (caCORRECT) and novel visualization methods (BioPNG, Gel Plots), which provide extra information about data quality unavailable in other microarray repositories. Third, it provides a user-curation capability through the familiar Wiki interface. Fourth, ArrayWiki provides users with simple text-based searches across all experiment meta-data, and exposes data to search engine crawlers (Semantic Agents) such as Google to further enhance data discovery. Conclusions Microarray data and meta information in ArrayWiki are distributed and visualized using a novel and compact data storage format, BioPNG. Also, they are open to the research community for curation, modification, and contribution. By making a small investment of time to learn the syntax and structure common to all sites running MediaWiki software, domain scientists and practioners can all contribute to make better use of microarray technologies in research and medical practices. ArrayWiki is available at . PMID:18541053

A microarray whole-genome gene expression dataset in a rat model of inflammatory corneal angiogenesis.

PubMed

Mukwaya, Anthony; Lindvall, Jessica M; Xeroudaki, Maria; Peebo, Beatrice; Ali, Zaheer; Lennikov, Anton; Jensen, Lasse Dahl Ejby; Lagali, Neil

2016-11-22

In angiogenesis with concurrent inflammation, many pathways are activated, some linked to VEGF and others largely VEGF-independent. Pathways involving inflammatory mediators, chemokines, and micro-RNAs may play important roles in maintaining a pro-angiogenic environment or mediating angiogenic regression. Here, we describe a gene expression dataset to facilitate exploration of pro-angiogenic, pro-inflammatory, and remodelling/normalization-associated genes during both an active capillary sprouting phase, and in the restoration of an avascular phenotype. The dataset was generated by microarray analysis of the whole transcriptome in a rat model of suture-induced inflammatory corneal neovascularisation. Regions of active capillary sprout growth or regression in the cornea were harvested and total RNA extracted from four biological replicates per group. High quality RNA was obtained for gene expression analysis using microarrays. Fold change of selected genes was validated by qPCR, and protein expression was evaluated by immunohistochemistry. We provide a gene expression dataset that may be re-used to investigate corneal neovascularisation, and may also have implications in other contexts of inflammation-mediated angiogenesis.

Evaluation of Two Outlier-Detection-Based Methods for Detecting Tissue-Selective Genes from Microarray Data

PubMed Central

Kadota, Koji; Konishi, Tomokazu; Shimizu, Kentaro

2007-01-01

Large-scale expression profiling using DNA microarrays enables identification of tissue-selective genes for which expression is considerably higher and/or lower in some tissues than in others. Among numerous possible methods, only two outlier-detection-based methods (an AIC-based method and Sprent’s non-parametric method) can treat equally various types of selective patterns, but they produce substantially different results. We investigated the performance of these two methods for different parameter settings and for a reduced number of samples. We focused on their ability to detect selective expression patterns robustly. We applied them to public microarray data collected from 36 normal human tissue samples and analyzed the effects of both changing the parameter settings and reducing the number of samples. The AIC-based method was more robust in both cases. The findings confirm that the use of the AIC-based method in the recently proposed ROKU method for detecting tissue-selective expression patterns is correct and that Sprent’s method is not suitable for ROKU. PMID:19936074

Identification of rat lung-specific microRNAs by micoRNA microarray: valuable discoveries for the facilitation of lung research.

PubMed

Wang, Yang; Weng, Tingting; Gou, Deming; Chen, Zhongming; Chintagari, Narendranath Reddy; Liu, Lin

2007-01-24

An important mechanism for gene regulation utilizes small non-coding RNAs called microRNAs (miRNAs). These small RNAs play important roles in tissue development, cell differentiation and proliferation, lipid and fat metabolism, stem cells, exocytosis, diseases and cancers. To date, relatively little is known about functions of miRNAs in the lung except lung cancer. In this study, we utilized a rat miRNA microarray containing 216 miRNA probes, printed in-house, to detect the expression of miRNAs in the rat lung compared to the rat heart, brain, liver, kidney and spleen. Statistical analysis using Significant Analysis of Microarray (SAM) and Tukey Honestly Significant Difference (HSD) revealed 2 miRNAs (miR-195 and miR-200c) expressed specifically in the lung and 9 miRNAs co-expressed in the lung and another organ. 12 selected miRNAs were verified by Northern blot analysis. The identified lung-specific miRNAs from this work will facilitate functional studies of miRNAs during normal physiological and pathophysiological processes of the lung.

Improvement in conduction velocity after optic neuritis measured with the multifocal VEP.

PubMed

Yang, E Bo; Hood, Donald C; Rodarte, Chris; Zhang, Xian; Odel, Jeffrey G; Behrens, Myles M

2007-02-01

To test the efficacy of the multifocal visual evoked potential (mfVEP) technique after long-term latency changes in optic neuritis (ON)/multiple sclerosis (MS), mfVEPs were recorded in 12 patients with ON/MS. Sixty local VEP responses were recorded simultaneously. mfVEP was recorded from both eyes of 12 patients with ON/MS. Patients were tested twice after recovery from acute ON episodes, which occurred in 14 of the 24 eyes. After recovery, all eyes had 20/20 or better visual acuity and normal visual fields as measured with static automated perimetry (SAP). The time between the two postrecovery tests varied from 6 to 56 months. Between test days, the visual fields obtained with SAP remained normal. Ten of the 14 affected eyes showed improvement in median latency on the mfVEP. Six of these eyes fell at or below (improved latency) the 96% confidence interval for the control eyes. None of the 10 initially unaffected eyes fell below the 96% lower limit. Although the improvement was widespread across the field, it did not include all regions. For the six eyes showing clear improvement, on average, 78% of the points had latencies that were shorter on test 2 than on test 1. A substantial percentage of ON/MS patients show a long-term improvement in conduction velocity. Because this improvement can be local, the mfVEP should allow these improvements to be monitored in patients with ON/MS.

Comparison of Predictable Smooth Ocular and Combined Eye-Head Tracking Behaviour in Patients with Lesions Affecting the Brainstem and Cerebellum

NASA Technical Reports Server (NTRS)

Grant, Michael P.; Leigh, R. John; Seidman, Scott H.; Riley, David E.; Hanna, Joseph P.

1992-01-01

We compared the ability of eight normal subjects and 15 patients with brainstem or cerebellar disease to follow a moving visual stimulus smoothly with either the eyes alone or with combined eye-head tracking. The visual stimulus was either a laser spot (horizontal and vertical planes) or a large rotating disc (torsional plane), which moved at one sinusoidal frequency for each subject. The visually enhanced Vestibulo-Ocular Reflex (VOR) was also measured in each plane. In the horizontal and vertical planes, we found that if tracking gain (gaze velocity/target velocity) for smooth pursuit was close to 1, the gain of combined eye-hand tracking was similar. If the tracking gain during smooth pursuit was less than about 0.7, combined eye-head tracking was usually superior. Most patients, irrespective of diagnosis, showed combined eye-head tracking that was superior to smooth pursuit; only two patients showed the converse. In the torsional plane, in which optokinetic responses were weak, combined eye-head tracking was much superior, and this was the case in both subjects and patients. We found that a linear model, in which an internal ocular tracking signal cancelled the VOR, could account for our findings in most normal subjects in the horizontal and vertical planes, but not in the torsional plane. The model failed to account for tracking behaviour in most patients in any plane, and suggested that the brain may use additional mechanisms to reduce the internal gain of the VOR during combined eye-head tracking. Our results confirm that certain patients who show impairment of smooth-pursuit eye movements preserve their ability to smoothly track a moving target with combined eye-head tracking.

Association between fundus autofluorescence and visual outcome in surgically closed macular holes.

PubMed

Lee, Young Seob; Yu, Seung-Young; Cho, Nam Suk; Kim, Moo Sang; Kim, Young Gyun; Kim, Eung Suk; Kwak, Hyung Woo

2013-06-01

To investigate the association between fundus autofluorescence (FAF) and visual acuity, recovery of foveal microstructure, and FAF in surgically closed macular holes. Twenty-six eyes with surgically closed macular hole were classified into two groups based on foveal FAF: normal autofluorescence (NAF) or increased autofluorescence (IAF). The association between foveal FAF and visual acuity was analyzed. In addition, we examined the relationship between recovery of the foveal microstructure assessed by spectral domain optical coherence tomography and FAF after macular hole surgery. At 1 month and 6 months after surgery, there were 9 NAF eyes and 17 IAF eyes. There were no differences between NAF and IAF eyes at 1 month and 6 months after surgery. Preoperative best-corrected visual acuity (logarithm of the minimum angle of resolution) did not differ between groups. Best-corrected visual acuity was significantly higher in the NAF group than in the IAF group at 1 month postoperatively (0.59 ± 0.34 vs. 0.91 ± 0.36, P = 0.044) and tended to be higher at 6 months (0.37 ± 0.38 vs. 0.69 ± 0.53, P = 0.126). Restoration of photoreceptor external limiting membrane differed significantly in 8 NAF eyes (89%) and 4 IAF eyes (24%) at postoperation 1 month (P = 0.001). After 6 months, external limiting membrane was restored in all 9 NAF eyes (100%) and in only 11 IAF eyes (65%) (P = 0.042). Fundus autofluorescence findings observed in surgically closed macular holes correlated with visual improvement and photoreceptor status. Eyes with visual improvement had restoration of normal foveal autofluorescence and retinal microstructure, whereas eyes with persistent foveal hyperautofluorescence did not achieve complete restoration of the retinal microstructure, and visual improvement was not as significant.

Influence of optic disc leakage on objective optic nerve head assessment in patients with uveitis.

PubMed

Heinz, Carsten; Kogelboom, Katy; Heiligenhaus, Arnd

2016-02-01

Secondary glaucoma is a common complication in patients with uveitis. Heidelberg Retina Tomography (HRT) and retinal nerve fiber layer (RNFL) thickness on optical coherence tomography (OCT) are widely used for examining optic nerve head changes. We evaluated these parameters in patients with uveitis and secondary glaucoma and with inflammatory papillary leakage on fluorescein angiography. Prospective single-center analysis of patients with uveitis, evaluating the impact of optic disc leakage on objective optic disc imaging parameters. Overall, 96 eyes of 59 patients were included. Papillary leakage was found in 42 eyes (43.8 %), and secondary glaucoma was found in 41 eyes (42.7 %). Glaucoma and papillary leakage were present in 12 (29 %) eyes with leakage and in 29 (54 %) eyes without leakage (p = 0.023). Neuroretinal rim area (p = 0.004), rim volume on HRT (p = 0.004), and RNFL thickness on OCT (p = 0.0008) were significantly increased in eyes with papillary leakage, while RNFL on HRT was unchanged (p = 0.255). When only eyes with normal IOP were examined, all objective parameters on OCT and HRT were significantly increased, whereas in eyes with secondary glaucoma, there was only a trend in the same direction, which did not reach significance. A comparison of eyes with secondary glaucoma and optic disc leakage to normal eyes with no glaucoma or leakage revealed no difference in any of the parameters. The objective parameters of optic nerve head imaging tools are significantly influenced by papillary leakage. In patients with secondary glaucoma and papillary leakage, these techniques are unable to detect and monitor glaucomatous damage.

In vivo imaging of palisades of Vogt in dry eye versus normal subjects using en-face spectral-domain optical coherence tomography.

PubMed

Ghouali, Wajdene; Tahiri Joutei Hassani, Rachid; Djerada, Zoubir; Liang, Hong; El Sanharawi, Mohamed; Labbé, Antoine; Baudouin, Christophe

2017-01-01

To evaluate a possible clinical application of spectral-domain optical coherence tomography (SD-OCT) using en-face module for the imaging of the corneoscleral limbus in normal subjects and dry eye patients. Seventy-six subjects were included in this study. Seventy eyes of 35 consecutive patients with dry eye disease and 82 eyes of 41 healthy control subjects were investigated. All subjects were examined with the Avanti RTVue® anterior segment OCT. En-face OCT images of the corneoscleral limbus were acquired in four quadrants (inferior, superior, nasal and temporal) and then were analyzed semi-quantitatively according to whether or not palisades of Vogt (POV) were visible. En-face OCT images were then compared to in vivo confocal microscopy (IVCM) in eleven eyes of 7 healthy and dry eye patients. En-face SD-OCT showed POV as a radially oriented network, located in superficial corneoscleral limbus, with a good correlation with IVCM features. It provided an easy and reproducible identification of POV without any special preparation or any direct contact, with a grading scale from 0 (no visualization) to 3 (high visualization). The POV were found predominantly in superior (P<0.001) and inferior (P<0.001) quadrants when compared to the nasal and temporal quadrants for all subjects examined. The visibility score decreased with age (P<0.001) and was lower in dry eye patients (P<0.01). In addition, the score decreased in accordance with the severity of dry eye disease (P<0.001). En-face SD-OCT is a non-contact imaging technique that can be used to evaluate the POV, thus providing valuable information about differences in the limbal anatomy of dry eye patients as compared to healthy patients.

Eye Growth in Term- And Preterm-Born Eyes Modeled From Magnetic Resonance Images

PubMed Central

Munro, Robert J.; Fulton, Anne B.; Chui, Toco Y. P.; Moskowitz, Anne; Ramamirtham, Ramkumar; Hansen, Ronald M.; Prabhu, Sanjay P.; Akula, James D.

2015-01-01

Purpose. We generated a model of eye growth and tested it against an eye known to develop abnormally, one with a history of retinopathy of prematurity (ROP). Methods. We reviewed extant magnetic resonance images (MRIs) from term and preterm-born patients for suitable images (n = 129). We binned subjects for analysis based upon postmenstrual age at birth (in weeks) and ROP history (“Term” ≥ 37, “Premature” ≤ 32 with no ROP, “ROP” ≤ 32 with ROP). We measured the axial positions and curvatures of the cornea, anterior and posterior lens, and inner retinal surface. We fit anterior chamber depth (ACD), posterior segment depth (PSD), axial length (AL), and corneal and lenticular curvatures with logistic growth curves that we then evaluated for significant differences. We also measured the length of rays from the centroid to the surface of the eye at 5° intervals, and described the length versus age relationship of each ray, Lray(x), using the same logistic growth curve. We determined the rate of ray elongation, Eray(x), from Lray dy/dx. Then, we estimated the scleral growth that accounted for Eray(x), G(x), at every age and position. Results. Relative to Term, development of ACD, PSD, AL, and corneal and lenticular curvatures was delayed in ROP eyes, but not Premature eyes. In Term infants, G(x) was fast and predominantly equatorial; in age-matched ROP eyes, maximal G(x) was offset by approximately 90°. Conclusions. We produced a model of normal eye growth in term-born subjects. Relative to normal, the ROP eye is characterized by delayed, abnormal growth. PMID:26024095

Changes in Tear Volume after 3% Diquafosol Treatment in Patients with Dry Eye Syndrome: An Anterior Segment Spectral-domain Optical Coherence Tomography Study.

PubMed

Lee, Kwan Bok; Koh, Kyung Min; Kwon, Young A; Song, Sang Wroul; Kim, Byoung Yeop; Chung, Jae Lim

2017-08-01

To evaluate changes in the tear meniscus area and tear meniscus height over time in patients with dry eye syndrome, using anterior segment spectral-domain optical coherence tomography after the instillation of 3% diquafosol ophthalmic solution. Sixty eyes from 30 patients with mild to moderate dry eye syndrome were included. Tear meniscus images acquired by anterior segment spectral-domain optical coherence tomography were analyzed using National Institutes of Health's image-analysis software (ImageJ 1.44p). Tear meniscus area and tear meniscus height were measured at baseline, 5 minutes, 10 minutes, and 30 minutes after instillation of a drop of diquafosol in one eye and normal saline in the other eye. Changes in ocular surface disease index score, tear film break-up time, corneal staining score by Oxford schema, and meibomian expressibility were also evaluated at baseline, and after 1 week and 1 month of a diquafosol daily regimen. Sixty eyes from 30 subjects (mean age, 29.3 years; 8 men and 22 women) were included. In eyes receiving diquafosol, tear volume was increased at 5 and 10 minutes compared with baseline. It was also higher than saline instilled eyes at 5, 10, and 30 minutes. Changes in tear volume with respect to baseline were not statistically different after the use of diquafosol for 1 month. Ocular surface disease index score, tear film break-up time, and Oxford cornea stain score were significantly improved after 1 week and 1 month of daily diquafosol instillation, but meibomian expressibility did not change. Topical diquafosol ophthalmic solution effectively increased tear volume for up to 30 minutes, compared to normal saline in patients with dry eye syndrome. © 2017 The Korean Ophthalmological Society

[Fundus autofluorescence. Has it a place in the management of diabetic macular edema?

PubMed

Zbiba, W; Baba, A; Bouayed, E; Daldoul, A

2016-11-01

Analyze the characteristics of fundus autofluorescence of diabetic macular edema and study the association between these characteristics and visual function. Our study included 18 patients (28 eyes) with clinically significant diabetic macular edema. All patients had a complete eye examination with a fundus autofluorescence imaging and optical coherence tomography. The central macular thickness and central macular volume were measured. The integrity of the inner segment-outer segment junction and the integrity of the external limiting membrane were also evaluated in the same area. Among the 28 eyes studied, 8 had normal autofluorescence. The remaining 20 eyes had abnormal autofluorescence: a hyper-cystoid autofluorescence in 5 eyes (25%), hyper-spot autofluorescence in 8 eyes (40%), and hypo-irregular autofluorescence in 5 eyes (25%). Best corrected visual acuity was significantly better in patients with normal autofluorescence and those with hyper-cystoid autofluorescence. There was no significant difference in central macular thickness (P=0.186) and central macular volume (P=0.191) between the four groups. The autofluorescence is a simple, fast, and non-invasive technique for the study of diabetic macular edema with good correlation to the visual function as well as to the extent of damage to the retina. It is, therefore, a possible alternative to other invasive imaging techniques in particular in the long term monitoring of diabetic macular edema. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Diurnal growth rhythms in the chicken eye: relation to myopia development and retinal dopamine levels.

PubMed

Weiss, S; Schaeffel, F

1993-04-01

1. If the eyes of young chickens are deprived of clear vision by translucent occluders, they develop considerable amounts of axial myopia within days. At the same time, the day time retinal dopamine levels drop by about 30%. Because the retinal dopamine levels of normally sighted chicks also differ diurnally and are low at night, we expected that the rate of axial eye growth might also differ during this time. 2. Unexpectedly, eyes grew in length only during the day (about 0.13 mm/day) and even shrank during the night (about -0.04 mm/night, average net growth +0.09 mm in 24 h). 3. If the eyes were occluded, they grew both during the day and also at night (average net growth: +0.16 mm in 24 h). Therefore, development of deprivation myopia was a result of the lack of growth inhibition at night rather than of excessive growth during the day when the actual deprivation occurred. 4. Suppression of dopaminergic retinal pathways by intravitreal injections of the neurotoxin 6-hydroxy-dopamine (6-OHDA) also suppressed development of deprivation myopia and it restored the growth inhibition at night. With normal visual experience, the drug had no effect on axial eye growth and refractive state. 5. Diurnal growth rhythms of the eyes disappeared under continuous light.(ABSTRACT TRUNCATED AT 250 WORDS)

Model-based variance-stabilizing transformation for Illumina microarray data.

PubMed

Lin, Simon M; Du, Pan; Huber, Wolfgang; Kibbe, Warren A

2008-02-01

Variance stabilization is a step in the preprocessing of microarray data that can greatly benefit the performance of subsequent statistical modeling and inference. Due to the often limited number of technical replicates for Affymetrix and cDNA arrays, achieving variance stabilization can be difficult. Although the Illumina microarray platform provides a larger number of technical replicates on each array (usually over 30 randomly distributed beads per probe), these replicates have not been leveraged in the current log2 data transformation process. We devised a variance-stabilizing transformation (VST) method that takes advantage of the technical replicates available on an Illumina microarray. We have compared VST with log2 and Variance-stabilizing normalization (VSN) by using the Kruglyak bead-level data (2006) and Barnes titration data (2005). The results of the Kruglyak data suggest that VST stabilizes variances of bead-replicates within an array. The results of the Barnes data show that VST can improve the detection of differentially expressed genes and reduce false-positive identifications. We conclude that although both VST and VSN are built upon the same model of measurement noise, VST stabilizes the variance better and more efficiently for the Illumina platform by leveraging the availability of a larger number of within-array replicates. The algorithms and Supplementary Data are included in the lumi package of Bioconductor, available at: www.bioconductor.org.

MMASS: an optimized array-based method for assessing CpG island methylation.

PubMed

Ibrahim, Ashraf E K; Thorne, Natalie P; Baird, Katie; Barbosa-Morais, Nuno L; Tavaré, Simon; Collins, V Peter; Wyllie, Andrew H; Arends, Mark J; Brenton, James D

2006-01-01

We describe an optimized microarray method for identifying genome-wide CpG island methylation called microarray-based methylation assessment of single samples (MMASS) which directly compares methylated to unmethylated sequences within a single sample. To improve previous methods we used bioinformatic analysis to predict an optimized combination of methylation-sensitive enzymes that had the highest utility for CpG-island probes and different methods to produce unmethylated representations of test DNA for more sensitive detection of differential methylation by hybridization. Subtraction or methylation-dependent digestion with McrBC was used with optimized (MMASS-v2) or previously described (MMASS-v1, MMASS-sub) methylation-sensitive enzyme combinations and compared with a published McrBC method. Comparison was performed using DNA from the cell line HCT116. We show that the distribution of methylation microarray data is inherently skewed and requires exogenous spiked controls for normalization and that analysis of digestion of methylated and unmethylated control sequences together with linear fit models of replicate data showed superior statistical power for the MMASS-v2 method. Comparison with previous methylation data for HCT116 and validation of CpG islands from PXMP4, SFRP2, DCC, RARB and TSEN2 confirmed the accuracy of MMASS-v2 results. The MMASS-v2 method offers improved sensitivity and statistical power for high-throughput microarray identification of differential methylation.

Gene ARMADA: an integrated multi-analysis platform for microarray data implemented in MATLAB.

PubMed

Chatziioannou, Aristotelis; Moulos, Panagiotis; Kolisis, Fragiskos N

2009-10-27

The microarray data analysis realm is ever growing through the development of various tools, open source and commercial. However there is absence of predefined rational algorithmic analysis workflows or batch standardized processing to incorporate all steps, from raw data import up to the derivation of significantly differentially expressed gene lists. This absence obfuscates the analytical procedure and obstructs the massive comparative processing of genomic microarray datasets. Moreover, the solutions provided, heavily depend on the programming skills of the user, whereas in the case of GUI embedded solutions, they do not provide direct support of various raw image analysis formats or a versatile and simultaneously flexible combination of signal processing methods. We describe here Gene ARMADA (Automated Robust MicroArray Data Analysis), a MATLAB implemented platform with a Graphical User Interface. This suite integrates all steps of microarray data analysis including automated data import, noise correction and filtering, normalization, statistical selection of differentially expressed genes, clustering, classification and annotation. In its current version, Gene ARMADA fully supports 2 coloured cDNA and Affymetrix oligonucleotide arrays, plus custom arrays for which experimental details are given in tabular form (Excel spreadsheet, comma separated values, tab-delimited text formats). It also supports the analysis of already processed results through its versatile import editor. Besides being fully automated, Gene ARMADA incorporates numerous functionalities of the Statistics and Bioinformatics Toolboxes of MATLAB. In addition, it provides numerous visualization and exploration tools plus customizable export data formats for seamless integration by other analysis tools or MATLAB, for further processing. Gene ARMADA requires MATLAB 7.4 (R2007a) or higher and is also distributed as a stand-alone application with MATLAB Component Runtime. Gene ARMADA provides a highly adaptable, integrative, yet flexible tool which can be used for automated quality control, analysis, annotation and visualization of microarray data, constituting a starting point for further data interpretation and integration with numerous other tools.

A comparative study of RNA-Seq and microarray data analysis on the two examples of rectal-cancer patients and Burkitt Lymphoma cells.

PubMed

Wolff, Alexander; Bayerlová, Michaela; Gaedcke, Jochen; Kube, Dieter; Beißbarth, Tim

2018-01-01

Pipeline comparisons for gene expression data are highly valuable for applied real data analyses, as they enable the selection of suitable analysis strategies for the dataset at hand. Such pipelines for RNA-Seq data should include mapping of reads, counting and differential gene expression analysis or preprocessing, normalization and differential gene expression in case of microarray analysis, in order to give a global insight into pipeline performances. Four commonly used RNA-Seq pipelines (STAR/HTSeq-Count/edgeR, STAR/RSEM/edgeR, Sailfish/edgeR, TopHat2/Cufflinks/CuffDiff)) were investigated on multiple levels (alignment and counting) and cross-compared with the microarray counterpart on the level of gene expression and gene ontology enrichment. For these comparisons we generated two matched microarray and RNA-Seq datasets: Burkitt Lymphoma cell line data and rectal cancer patient data. The overall mapping rate of STAR was 98.98% for the cell line dataset and 98.49% for the patient dataset. Tophat's overall mapping rate was 97.02% and 96.73%, respectively, while Sailfish had only an overall mapping rate of 84.81% and 54.44%. The correlation of gene expression in microarray and RNA-Seq data was moderately worse for the patient dataset (ρ = 0.67-0.69) than for the cell line dataset (ρ = 0.87-0.88). An exception were the correlation results of Cufflinks, which were substantially lower (ρ = 0.21-0.29 and 0.34-0.53). For both datasets we identified very low numbers of differentially expressed genes using the microarray platform. For RNA-Seq we checked the agreement of differentially expressed genes identified in the different pipelines and of GO-term enrichment results. In conclusion the combination of STAR aligner with HTSeq-Count followed by STAR aligner with RSEM and Sailfish generated differentially expressed genes best suited for the dataset at hand and in agreement with most of the other transcriptomics pipelines.

Retinal thickness after vitrectomy and internal limiting membrane peeling for macular hole and epiretinal membrane

PubMed Central

Kumagai, Kazuyuki; Ogino, Nobuchika; Furukawa, Mariko; Hangai, Masanori; Kazama, Shigeyasu; Nishigaki, Shirou; Larson, Eric

2012-01-01

Purpose To determine the retinal thickness (RT), after vitrectomy with internal limiting membrane (ILM) peeling, for an idiopathic macular hole (MH) or an epiretinal membrane (ERM). Also, to investigate the effect of a dissociated optic nerve fiber layer (DONFL) appearance on RT. Methods A non-randomized, retrospective chart review was performed for 159 patients who had successful closure of a MH, with (n = 148), or without (n = 11), ILM peeling. Also studied were 117 patients who had successful removal of an ERM, with (n = 104), or without (n = 13), ILM peeling. The RT of the nine Early Treatment Diabetic Retinopathy Study areas was measured by spectral domain optical coherence tomography (SD-OCT). In the MH-with-ILM peeling and ERM-with-ILM peeling groups, the RT of the operated eyes was compared to the corresponding areas of normal fellow eyes. The inner temporal/inner nasal ratio (TNR) was used to assess the effect of ILM peeling on RT. The effects of DONFL appearance on RT were evaluated in only the MH-with-ILM peeling group. Results In the MH-with-ILM peeling group, the central, inner nasal, and outer nasal areas of the retina of operated eyes were significantly thicker than the corresponding areas of normal fellow eyes. In addition, the inner temporal, outer temporal, and inner superior retina was significantly thinner than in the corresponding areas of normal fellow eyes. Similar findings were observed regardless of the presence of a DONFL appearance. In the ERM-with-ILM peeling group, the retina of operated eyes was significantly thicker in all areas, except the inner and outer temporal areas. In the MH-with-ILM peeling group, the TNR was 0.86 in operated eyes, and 0.96 in fellow eyes (P < 0.001). In the ERM-with-ILM peeling group, the TNR was 0.84 in operated eyes, and 0.95 in fellow eyes (P < 0.001). TNR in operated eyes of the MH-without-ILM peeling group was 0.98, which was significantly greater than that of the MH-with-ILM peeling group (P < 0.001). TNR in the operated eyes of the ERM-without-ILM peeling group was 0.98, which was significantly greater than that of ERM-with-ILM peeling group (P < 0.001). Conclusion The thinning of the temporal retina and thickening of the nasal retina after ILM peeling does not appear to be disease-specific. In addition, changes in RT after ILM peeling are not related to the presence of a DONFL appearance. PMID:22654493

Analysis of pupil and corneal wave aberration data supplied by the SN CT 1000 topography system

NASA Astrophysics Data System (ADS)

Comastri, S. A.; Martin, G.; Pfortner, T.

2006-11-01

Ocular aberrations depend on pupil size and centring and the retinal image quality under natural conditions differs from that corresponding to laboratory ones. In the present article, pupil and wave aberration data supplied by the Shin Nippon CT 1000 (SN CT 1000) topography system are analysed. Two groups of eyes under natural viewing conditions are considered ((260+/-20) lux at the eye under study). The first group consists of 10 normal eyes (-1.25 to 3 D sphere; 0 to -1.75 D cylinder) of five young subjects (age between 18 and 33 years). For this group, five determinations per eye are performed and the repeatability of results is analysed. Pupil centre is displaced from corneal vertex towards the temporal region, the largest displacement being (0.5+/-0.1) mm. The variation of pupil diameter in each eye is less than 21% while the inter-subject variability is large since diameters are between (3+/-0.3) and (5.3+/-0.6) mm. Aberrations are evaluated for two different pupil sizes, the natural one and a fictitious one of 6 mm. The corneal higher-order root-mean square wavefront error (RMSHO) for a 6 mm pupil centred in the corneal vertex, averaged across all eyes, is (0.37+/-0.06) [mu]m while, considering the natural pupil diameter, the average in each eye is significantly lower, up to eight times smaller. The fourth-order spherical aberration is an important aberration in the considered eyes, its maximum value for a 6 mm pupil being (0.38+/-0.02) [mu]m. The second group consists of 24 eyes of 12 subjects (age between 25 and 68 years) such that four eyes are of normal adults (1.25 to +6 D sphere; 0 to -0.5 D cylinder), eight have astigmatisms (-5.5 to +3.25 D sphere; -1.5 to -4.5 D cylinder), six have post-refractive surgery (+0.5 to +3.5 D sphere; -0.5 to -4 D cylinder) and six have keratoconus (-9.5 to +1 D sphere; -1 to -4.5 D cylinder). For this group only one determination per eye is performed. Pupil centre is displaced from corneal vertex towards the temporal region except in cases of keratoconus, where there can be a dominant upwards displacement. Pupil diameters are between 2.7 and 5.6 mm. The corneal higher order root mean square wavefront error for a 6 mm pupil ranges between 0.3 (normal eye) and 5.3 [mu]m (keratoconus).

Individual A-Scan Signal Normalization Between Two Spectral Domain Optical Coherence Tomography Devices

PubMed Central

Chen, Chieh-Li; Ishikawa, Hiroshi; Wollstein, Gadi; Ling, Yun; Bilonick, Richard A.; Kagemann, Larry; Sigal, Ian A.; Schuman, Joel S.

2013-01-01

Purpose. We developed a method to normalize optical coherence tomography (OCT) signal profiles from two spectral-domain (SD) OCT devices so that the comparability between devices increases. Methods. We scanned 21 eyes from 14 healthy and 7 glaucoma subjects with two SD-OCT devices on the same day, with equivalent cube scan patterns centered on the fovea (Cirrus HD-OCT and RTVue). Foveola positions were selected manually and used as the center for registration of the corresponding images. A-scan signals were sampled 1.8 mm from the foveola in the temporal, superior, nasal, and inferior quadrants. After oversampling and rescaling RTVue data along the Z-axis to match the corresponding Cirrus data format, speckle noise reduction and amplitude normalization were applied. For comparison between normalized A-scan profiles, mean absolute difference in amplitude in percentage was measured at each sampling point. As a reference, the mean absolute difference between two Cirrus scans on the same eye also was measured. Results. The mean residual of the A-scan profile amplitude was reduced significantly after signal normalization (12.7% vs. 6.2%, P < 0.0001, paired t-test). All four quadrants also showed statistically significant reduction (all P < 0.0001). Mean absolute difference after normalization was smaller than the one between two Cirrus scans. No performance difference was detected between health and glaucomatous eyes. Conclusions. The reported signal normalization method successfully reduced the A-scan profile differences between two SD-OCT devices. This signal normalization processing may improve the direct comparability of OCT image analysis and measurement on various devices. PMID:23611992

Transcriptome analysis of the planarian eye identifies ovo as a specific regulator of eye regeneration.

PubMed

Lapan, Sylvain W; Reddien, Peter W

2012-08-30

Among the millions of invertebrate species with visual systems, the genetic basis of eye development and function is well understood only in Drosophila melanogaster. We describe an eye transcriptome for the planarian Schmidtea mediterranea. Planarian photoreceptors expressed orthologs of genes required for phototransduction and microvillus structure in Drosophila and vertebrates, and optic pigment cells expressed solute transporters and melanin synthesis enzymes similar to those active in the vertebrate retinal pigment epithelium. Orthologs of several planarian eye genes, such as bestrophin-1 and Usher syndrome genes, cause eye defects in mammals when perturbed and were not previously described to have roles in invertebrate eyes. Five previously undescribed planarian eye transcription factors were required for normal eye formation during head regeneration. In particular, a conserved, transcription-factor-encoding ovo gene was expressed from the earliest stages of eye regeneration and was required for regeneration of all cell types of the eye. Copyright © 2012 The Authors. Published by Elsevier Inc. All rights reserved.

Ewing's Sarcoma: An Analysis of miRNA Expression Profiles and Target Genes in Paraffin-Embedded Primary Tumor Tissue.

PubMed

Parafioriti, Antonina; Bason, Caterina; Armiraglio, Elisabetta; Calciano, Lucia; Daolio, Primo Andrea; Berardocco, Martina; Di Bernardo, Andrea; Colosimo, Alessia; Luksch, Roberto; Berardi, Anna C

2016-04-30

The molecular mechanism responsible for Ewing's Sarcoma (ES) remains largely unknown. MicroRNAs (miRNAs), a class of small non-coding RNAs able to regulate gene expression, are deregulated in tumors and may serve as a tool for diagnosis and prediction. However, the status of miRNAs in ES has not yet been thoroughly investigated. This study compared global miRNAs expression in paraffin-embedded tumor tissue samples from 20 ES patients, affected by primary untreated tumors, with miRNAs expressed in normal human mesenchymal stromal cells (MSCs) by microarray analysis. A miRTarBase database was used to identify the predicted target genes for differentially expressed miRNAs. The miRNAs microarray analysis revealed distinct patterns of miRNAs expression between ES samples and normal MSCs. 58 of the 954 analyzed miRNAs were significantly differentially expressed in ES samples compared to MSCs. Moreover, the qRT-PCR analysis carried out on three selected miRNAs showed that miR-181b, miR-1915 and miR-1275 were significantly aberrantly regulated, confirming the microarray results. Bio-database analysis identified BCL-2 as a bona fide target gene of the miR-21, miR-181a, miR-181b, miR-29a, miR-29b, miR-497, miR-195, miR-let-7a, miR-34a and miR-1915. Using paraffin-embedded tissues from ES patients, this study has identified several potential target miRNAs and one gene that might be considered a novel critical biomarker for ES pathogenesis.

At what scale should microarray data be analyzed?

PubMed

Huang, Shuguang; Yeo, Adeline A; Gelbert, Lawrence; Lin, Xi; Nisenbaum, Laura; Bemis, Kerry G

2004-01-01

The hybridization intensities derived from microarray experiments, for example Affymetrix's MAS5 signals, are very often transformed in one way or another before statistical models are fitted. The motivation for performing transformation is usually to satisfy the model assumptions such as normality and homogeneity in variance. Generally speaking, two types of strategies are often applied to microarray data depending on the analysis need: correlation analysis where all the gene intensities on the array are considered simultaneously, and gene-by-gene ANOVA where each gene is analyzed individually. We investigate the distributional properties of the Affymetrix GeneChip signal data under the two scenarios, focusing on the impact of analyzing the data at an inappropriate scale. The Box-Cox type of transformation is first investigated for the strategy of pooling genes. The commonly used log-transformation is particularly applied for comparison purposes. For the scenario where analysis is on a gene-by-gene basis, the model assumptions such as normality are explored. The impact of using a wrong scale is illustrated by log-transformation and quartic-root transformation. When all the genes on the array are considered together, the dependent relationship between the expression and its variation level can be satisfactorily removed by Box-Cox transformation. When genes are analyzed individually, the distributional properties of the intensities are shown to be gene dependent. Derivation and simulation show that some loss of power is incurred when a wrong scale is used, but due to the robustness of the t-test, the loss is acceptable when the fold-change is not very large.

Comparison of two schemes for automatic keyword extraction from MEDLINE for functional gene clustering.

PubMed

Liu, Ying; Ciliax, Brian J; Borges, Karin; Dasigi, Venu; Ram, Ashwin; Navathe, Shamkant B; Dingledine, Ray

2004-01-01

One of the key challenges of microarray studies is to derive biological insights from the unprecedented quatities of data on gene-expression patterns. Clustering genes by functional keyword association can provide direct information about the nature of the functional links among genes within the derived clusters. However, the quality of the keyword lists extracted from biomedical literature for each gene significantly affects the clustering results. We extracted keywords from MEDLINE that describes the most prominent functions of the genes, and used the resulting weights of the keywords as feature vectors for gene clustering. By analyzing the resulting cluster quality, we compared two keyword weighting schemes: normalized z-score and term frequency-inverse document frequency (TFIDF). The best combination of background comparison set, stop list and stemming algorithm was selected based on precision and recall metrics. In a test set of four known gene groups, a hierarchical algorithm correctly assigned 25 of 26 genes to the appropriate clusters based on keywords extracted by the TDFIDF weighting scheme, but only 23 og 26 with the z-score method. To evaluate the effectiveness of the weighting schemes for keyword extraction for gene clusters from microarray profiles, 44 yeast genes that are differentially expressed during the cell cycle were used as a second test set. Using established measures of cluster quality, the results produced from TFIDF-weighted keywords had higher purity, lower entropy, and higher mutual information than those produced from normalized z-score weighted keywords. The optimized algorithms should be useful for sorting genes from microarray lists into functionally discrete clusters.

Expression profile of circular RNAs in human gastric cancer tissues

PubMed Central

Huang, You-Sheng; Jie, Na; Zou, Ke-Jian; Weng, Yang

2017-01-01

Circular RNAs (circRNAs) represent a newly identified class of non-coding RNA molecules, which interfere with gene transcription by adsorbing microRNAs (miRNAs). CircRNAs serve important roles in disease development and have the potential to serve as a novel class of biomarkers for clinical diagnosis. However, the role of circRNAs in the occurrence and development of gastric cancer (GC) remains unclear. In the present study, the expression profiles of circRNAs were compared between GC and adjacent normal tissues using a circRNA microarray, following which quantitative polymerase chain reaction (qPCR) was used to confirm the results of the circRNA microarray. Compared with the adjacent, normal mucosal tissues, 16 circRNAs were upregulated and 84 circRNAs were downregulated in GC. A total of 10 circRNAs were selected for validation in three pairs of GC and adjacent noncancerous tissues. The qPCR results were consistent with the findings of the microarray-based expression analysis. Of the circRNAs studied, only circRNA-0026 (hsa_circ_0000026) exhibited significantly different expression in GC (2.8-fold, P=0.001). Furthermore, online Database for Annotation, Visualization and Integrated Discovery annotation was used to predict circRNA-targeted miRNA-gene interactions. The analysis revealed that circRNA-0026 may regulate RNA transcription, RNA metabolism, gene expression, gene silencing and other biological functions in GC. In conclusion, differential expression of circRNAs may be associated with GC tumorigenesis, and circRNA-0026 is a promising biomarker for GC diagnosis and targeted therapy. PMID:28737829

EFEMP1 as a novel DNA methylation marker for prostate cancer: array-based DNA methylation and expression profiling.

PubMed

Kim, Yong-June; Yoon, Hyung-Yoon; Kim, Seon-Kyu; Kim, Young-Won; Kim, Eun-Jung; Kim, Isaac Yi; Kim, Wun-Jae

2011-07-01

Abnormal DNA methylation is associated with many human cancers. The aim of the present study was to identify novel methylation markers in prostate cancer (PCa) by microarray analysis and to test whether these markers could discriminate normal and PCa cells. Microarray-based DNA methylation and gene expression profiling was carried out using a panel of PCa cell lines and a control normal prostate cell line. The methylation status of candidate genes in prostate cell lines was confirmed by real-time reverse transcriptase-PCR, bisulfite sequencing analysis, and treatment with a demethylation agent. DNA methylation and gene expression analysis in 203 human prostate specimens, including 106 PCa and 97 benign prostate hyperplasia (BPH), were carried out. Further validation using microarray gene expression data from the Gene Expression Omnibus (GEO) was carried out. Epidermal growth factor-containing fibulin-like extracellular matrix protein 1 (EFEMP1) was identified as a lead candidate methylation marker for PCa. The gene expression level of EFEMP1 was significantly higher in tissue samples from patients with BPH than in those with PCa (P < 0.001). The sensitivity and specificity of EFEMP1 methylation status in discriminating between PCa and BPH reached 95.3% (101 of 106) and 86.6% (84 of 97), respectively. From the GEO data set, we confirmed that the expression level of EFEMP1 was significantly different between PCa and BPH. Genome-wide characterization of DNA methylation profiles enabled the identification of EFEMP1 aberrant methylation patterns in PCa. EFEMP1 might be a useful indicator for the detection of PCa.

Rapid, Accurate, and Non-Invasive Measurement of Zebrafish Axial Length and Other Eye Dimensions Using SD-OCT Allows Longitudinal Analysis of Myopia and Emmetropization

PubMed Central

Collery, Ross F.; Veth, Kerry N.; Dubis, Adam M.; Carroll, Joseph; Link, Brian A.

2014-01-01

Refractive errors in vision can be caused by aberrant axial length of the eye, irregular corneal shape, or lens abnormalities. Causes of eye length overgrowth include multiple genetic loci, and visual parameters. We evaluate zebrafish as a potential animal model for studies of the genetic, cellular, and signaling basis of emmetropization and myopia. Axial length and other eye dimensions of zebrafish were measured using spectral domain-optical coherence tomography (SD-OCT). We used ocular lens and body metrics to normalize and compare eye size and relative refractive error (difference between observed retinal radial length and controls) in wild-type and lrp2 zebrafish. Zebrafish were dark-reared to assess effects of visual deprivation on eye size. Two relative measurements, ocular axial length to body length and axial length to lens diameter, were found to accurately normalize comparisons of eye sizes between different sized fish (R2 = 0.9548, R2 = 0.9921). Ray-traced focal lengths of wild-type zebrafish lenses were equal to their retinal radii, while lrp2 eyes had longer retinal radii than focal lengths. Both genetic mutation (lrp2) and environmental manipulation (dark-rearing) caused elongated eye axes. lrp2 mutants had relative refractive errors of −0.327 compared to wild-types, and dark-reared wild-type fish had relative refractive errors of −0.132 compared to light-reared siblings. Therefore, zebrafish eye anatomy (axial length, lens radius, retinal radius) can be rapidly and accurately measured by SD-OCT, facilitating longitudinal studies of regulated eye growth and emmetropization. Specifically, genes homologous to human myopia candidates may be modified, inactivated or overexpressed in zebrafish, and myopia-sensitizing conditions used to probe gene-environment interactions. Our studies provide foundation for such investigations into genetic contributions that control eye size and impact refractive errors. PMID:25334040

Acuity-independent effects of visual deprivation on human visual cortex

PubMed Central

Hou, Chuan; Pettet, Mark W.; Norcia, Anthony M.

2014-01-01

Visual development depends on sensory input during an early developmental critical period. Deviation of the pointing direction of the two eyes (strabismus) or chronic optical blur (anisometropia) separately and together can disrupt the formation of normal binocular interactions and the development of spatial processing, leading to a loss of stereopsis and visual acuity known as amblyopia. To shed new light on how these two different forms of visual deprivation affect the development of visual cortex, we used event-related potentials (ERPs) to study the temporal evolution of visual responses in patients who had experienced either strabismus or anisometropia early in life. To make a specific statement about the locus of deprivation effects, we took advantage of a stimulation paradigm in which we could measure deprivation effects that arise either before or after a configuration-specific response to illusory contours (ICs). Extraction of ICs is known to first occur in extrastriate visual areas. Our ERP measurements indicate that deprivation via strabismus affects both the early part of the evoked response that occurs before ICs are formed as well as the later IC-selective response. Importantly, these effects are found in the normal-acuity nonamblyopic eyes of strabismic amblyopes and in both eyes of strabismic patients without amblyopia. The nonamblyopic eyes of anisometropic amblyopes, by contrast, are normal. Our results indicate that beyond the well-known effects of strabismus on the development of normal binocularity, it also affects the early stages of monocular feature processing in an acuity-independent fashion. PMID:25024230

Eye movements during visual search in patients with glaucoma

PubMed Central

2012-01-01

Background Glaucoma has been shown to lead to disability in many daily tasks including visual search. This study aims to determine whether the saccadic eye movements of people with glaucoma differ from those of people with normal vision, and to investigate the association between eye movements and impaired visual search. Methods Forty patients (mean age: 67 [SD: 9] years) with a range of glaucomatous visual field (VF) defects in both eyes (mean best eye mean deviation [MD]: –5.9 (SD: 5.4) dB) and 40 age-related people with normal vision (mean age: 66 [SD: 10] years) were timed as they searched for a series of target objects in computer displayed photographs of real world scenes. Eye movements were simultaneously recorded using an eye tracker. Average number of saccades per second, average saccade amplitude and average search duration across trials were recorded. These response variables were compared with measurements of VF and contrast sensitivity. Results The average rate of saccades made by the patient group was significantly smaller than the number made by controls during the visual search task (P = 0.02; mean reduction of 5.6% (95% CI: 0.1 to 10.4%). There was no difference in average saccade amplitude between the patients and the controls (P = 0.09). Average number of saccades was weakly correlated with aspects of visual function, with patients with worse contrast sensitivity (PR logCS; Spearman’s rho: 0.42; P = 0.006) and more severe VF defects (best eye MD; Spearman’s rho: 0.34; P = 0.037) tending to make less eye movements during the task. Average detection time in the search task was associated with the average rate of saccades in the patient group (Spearman’s rho = −0.65; P < 0.001) but this was not apparent in the controls. Conclusions The average rate of saccades made during visual search by this group of patients was fewer than those made by people with normal vision of a similar average age. There was wide variability in saccade rate in the patients but there was an association between an increase in this measure and better performance in the search task. Assessment of eye movements in individuals with glaucoma might provide insight into the functional deficits of the disease. PMID:22937814

The pathology of dry eye: the interaction between the ocular surface and lacrimal glands.

PubMed

Stern, M E; Beuerman, R W; Fox, R I; Gao, J; Mircheff, A K; Pflugfelder, S C

1998-11-01

Most dry-eye symptoms result from an abnormal, nonlubricative ocular surface that increases shear forces under the eyelids and diminishes the ability of the ocular surface to respond to environmental challenges. This ocular-surface dysfunction may result from immunocompromise due to systemic autoimmune disease or may occur locally from a decrease in systemic androgen support to the lacrimal gland as seen in aging, most frequently in the menopausal female. Components of the ocular surface (cornea, conjunctiva, accessory lacrimal glands, and meibomian glands), the main lacrimal gland, and interconnecting innervation act as a functional unit. When one portion is compromised, normal lacrimal support of the ocular surface is impaired. Resulting immune-based inflammation can lead to lacrimal gland and neural dysfunction. This progression yields the OS symptoms associated with dry eye. Restoration of lacrimal function involves resolution of lymphocytic activation and inflammation. This has been demonstrated in the MRL/lpr mouse using systemic androgens or cyclosporine and in the dry-eye dog using topical cyclosporine. The efficacy of cyclosporine may be due to its immunomodulatory and antiinflammatory (phosphatase inhibitory capability) functions on the ocular surface, resulting in a normalization of nerve traffic. Although the etiologies of dry eye are varied, common to all ocular-surface disease is an underlying cytokine/receptor-mediated inflammatory process. By treating this process, it may be possible to normalize the ocular surface/lacrimal neural reflex and facilitate ocular surface healing.

Case-controlled clinical and histopathological study of conjunctivochalasis.

PubMed

Francis, I C; Chan, D G; Kim, P; Wilcsek, G; Filipic, M; Yong, J; Coroneo, M T

2005-03-01

Conjunctivochalasis, a secondary cause of the watery eye, is frequently seen in the older age group as an elevation of the bulbar conjunctiva lying along the lateral or central lower lid margin. A prospective, interventional, case-controlled clinical and histopathological study was conducted. The relevant features of 18 patients (29 eyes) who had their conjunctivochalasis resected as part of the surgical management of their watery eye syndrome were examined. In the control group, tissue was obtained from an age matched series of 24 normal subjects undergoing routine cataract surgery. 24 controls (24 specimens) and 18 patients (29 specimens) had conjunctival strip biopsies, taken from the usual lid margin level bulbar conjunctiva in line with the inferior limbus (controls), and the clinically apparent conjunctivochalasis (patients). These were submitted for histological study. 23 of 24 control sections demonstrated normal conjunctival variation. Four of 29 patient specimens demonstrated a chronic non-granulomatous conjunctivitis, while three eyes of the patient group (two patients) demonstrated features of elastosis. Of the four patients who had the inflammatory infiltrates, three had functional nasolacrimal duct obstructions (FNLDOs) and one had a primary acquired nasolacrimal duct obstruction (PANDO). Of the two patients who had elastosis, one had an FNLDO and the other had normal lacrimal drainage and was Jones 1 positive. Six of 18 patients--that is, seven of 29 specimens of conjunctivochalasis demonstrated signs of elastosis or of chronic non-granulomatous inflammation. Clinically, patients had a spectrum of aetiologies of their watery eye syndrome.

Determination of reference values for intraocular pressure and Schirmer tear test results in clinically normal domestic donkeys (Equus asinus).

PubMed

Selk Ghaffari, Masoud; Sabzevari, Amin; Ghamsari, SeyedMehdi; Shad, Hussein

2017-11-25

This study was conducted to establish normal reference range for the Schirmer tear test (STT) and intraocular pressure (IOP) in clinically normal donkeys for use in clinical practice. Sixteen adult Ethiopian domestic donkeys were used in this study. Complete ophthalmic examinations were performed without chemical restraint. STT values were evaluated in both eyes of all donkeys using a commercial STT strip. IOP was measured in both eyes with a Tono-Pen Vet (Reichert. USA) without using regional nerve blocks. STT values for all eyes (n=32) were 22.1±6.9 mm/minute with a range of 13-35 mm/minute. Comparison of mean STT values between right (n=16) and left eyes (n=16) showed no differences (P=0.6). Mean ±sd IOP values by applanation tonometry were 17.8±3.7 mmHg (range 13.5-24.5 mmHg). Comparison of mean IOP values between right (n=16) and left eyes (n=16) showed no differences (P=0.7). This initial survey provides means and ranges for IOP and STT values in donkeys. These data will assist veterinary ophthalmologists in more accurate diagnosis and management of ophthalmic diseases in donkeys, including keratoconjunctivitis sicca and glaucoma. © British Veterinary Association (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Alcohol- and light-induced electro-oculographic responses in age-related macular degeneration & central serous chorioretinopathy. alcohol- and light-induced EOG responses in ARMD & CSC.

PubMed

Wu, Kathy H C; Marmor, Michael F

2005-01-01

The non-photic electro-oculographic (EOG) response induced by alcohol has been proposed as an indicator of retinal pigment epithelial (RPE) integrity, and reported to be abnormal in age-related macular degeneration (ARMD). To evaluate this proposal, we have measured the alcohol-EOG as well as the ISCEV-standard EOG in patients with ARMD (n=11 patients, 4 eyes with drusen, 8 eyes with 'dry' and 7 eyes with 'wet' lesions) and central serous chorioretinopathy (CSC, n=11 patients, 7 eyes with active and 6 eyes with inactive lesions), compared with 29 normal controls. We recorded the alcohol-induced EOG response after a single oral administration of ethanol at 160 mg/kg, followed by an ISCEV-standard EOG. Blood alcohol levels were monitored with a breath analyzer. We found that neither the alcohol-EOG nor the light-induced EOG response showed any difference between either ARMD or CSC patients and normal controls. Nor was there difference among eyes of different ARMD or CSC subgroups. In addition, blood alcohol concentrations near the time of the alcohol-EOG peak showed no obvious relationship with peak/baseline ratios. These data suggest that neither the alcohol- nor the light-induced EOG is a sensitive indicator of these diseases.

Fundus autofluorescence and optical coherence tomographic findings in acute zonal occult outer retinopathy.

PubMed

Fujiwara, Takamitsu; Imamura, Yutaka; Giovinazzo, Vincent J; Spaide, Richard F

2010-09-01

The purpose of this study was to investigate the fundus autofluorescence and optical coherence tomography findings in eyes with acute zonal occult outer retinopathy (AZOOR). A retrospective observational case series of the fundus autofluorescence and spectral domain optical coherence tomography in a series of patients with AZOOR. There were 19 eyes of 11 patients (10 women), who had a mean age of 49.1 +/- 13.9 years. Fundus autofluorescence abnormalities were seen in 17 of the 19 eyes, were more common in the peripapillary area, and were smaller in extent than the optical coherence tomography abnormalities. Nine eyes showed progression of hypoautofluorescence area during the mean follow-up of 69.7 months. The mean thickness of the photoreceptor layer at fovea was 177 microm in eyes with AZOOR, which was significantly thinner than controls (193 microm, P = 0.049). Abnormal retinal laminations were found in 12 eyes and were located over areas of loss of the photoreceptors. The subfoveal choroidal thickness was 243 microm, which is normal. Fundus autofluorescence abnormalities in AZOOR showed distinct patterns of retinal pigment epithelial involvement, which may be progressive. Thinning of photoreceptor cell layer with loss of the outer segments and abnormal inner retinal lamination in the context of a normal choroid are commonly found in AZOOR.

Fixation stability of the upward gaze in patients with myasthenia gravis: an eye-tracker study

PubMed Central

Mihara, Miharu; Hayashi, Atsushi; Fujita, Kazuya; Kakeue, Ken; Tamura, Ryoi

2017-01-01

Objective To quantify fixation stability of the upward gaze in patients with myasthenia gravis (MG) using an eye tracker. Methods and analysis In this study, 21 normal subjects, 5 patients with MG with diplopia, 5 patients with MG without diplopia and 6 patients with superior oblique (SO) palsy were included. Subjects fixated on a target in the upward direction for 1 min. The horizontal (X) and vertical (Y) eye positions were recorded using an eye tracker. Fixation stability was first quantified using the bivariate contour ellipse areas (BCEA) of fixation points as an index of whole stability. Then, the SDs of the X and Y eye positions (SDX and SDY, respectively) were quantified as indices of directional stability, with the data divided into three 20 s fractions to detect temporal fixation fluctuation. Results BCEAs were larger in patients with MG (both with and without diplopia) than normal subjects and patients with SO palsy, without significant differences among the three 20 s fractions. Compared with normal subjects, SDXs were larger only in patients with MG with diplopia; SDYs were larger in both patients with MG with and without diplopia. In addition, SDYs in patients with MG with diplopia were larger than those in patients with MG without diplopia and patients with SO palsy. Furthermore, a significant difference among the three 20 s fractions was detected for SDYs in patients with MG with diplopia. Conclusion Patients with MG, especially those with diplopia, exhibit fixation instability in the upward gaze. Non-invasive quantification of fixation stability with an eye tracker is useful for precisely identifying MG-specific fatigue characteristics. Trial registration number UMIN000023468; pre-results. PMID:29354719

Effects of Foveal Ablation on the Pattern of Peripheral Refractive Errors in Normal and Form-deprived Infant Rhesus Monkeys (Macaca mulatta)

PubMed Central

Huang, Juan; Hung, Li-Fang

2011-01-01

Purpose. The purpose of this study was to determine whether visual signals from the fovea contribute to the changes in the pattern of peripheral refractions associated with form deprivation myopia in monkeys. Methods. Monocular form-deprivation was produced in 18 rhesus monkeys by securing diffusers in front of their treated eyes between 22 ± 2 and 155 ± 17 days of age. In eight of these form-deprived monkeys, the fovea and most of the perifovea of the treated eye were ablated by laser photocoagulation at the start of the diffuser-rearing period. Each eye's refractive status was measured by retinoscopy along the pupillary axis and at 15° intervals along the horizontal meridian to eccentricities of 45°. Control data were obtained from 12 normal monkeys and five monkeys that had monocular foveal ablations and were subsequently reared with unrestricted vision. Results. Foveal ablation, by itself, did not produce systematic alterations in either the central or peripheral refractive errors of the treated eyes. In addition, foveal ablation did not alter the patterns of peripheral refractions in monkeys with form-deprivation myopia. The patterns of peripheral refractive errors in the two groups of form-deprived monkeys, either with or without foveal ablation, were qualitatively similar (treated eyes: F = 0.31, P = 0.74; anisometropia: F = 0.61, P = 0.59), but significantly different from those found in the normal monkeys (F = 8.46 and 9.38 respectively, P < 0.05). Conclusions. Central retinal signals do not contribute in an essential way to the alterations in eye shape that occur during the development of vision-induced axial myopia. PMID:21693598

The effects of topical diclofenac, topical flurbiprofen, and humidity on corneal sensitivity in normal dogs.

PubMed

Dorbandt, Daniel M; Labelle, Amber L; Mitchell, Mark A; Hamor, Ralph E

2017-03-01

To determine the immediate and chronic effects of topical 0.1% diclofenac and 0.03% flurbiprofen on corneal sensitivity in normal canine eyes. Eighteen normal, nonbrachycephalic dogs. A prospective, randomized, masked, crossover study was performed. To determine the immediate effects associated with treatment, the study drug was instilled into the eye every 5 min for five doses, and corneal sensitivity of treated and untreated eyes was obtained prior to treatment and every 15 min post-treatment for 60 min. To determine the chronic effects, the study drug was instilled every 12 h for 30 days, and corneal sensitivity of treated and untreated eyes was obtained prior to treatment on days 0 and 30. A washout period of at least 30 days occurred between drug crossover. Ambient temperature and humidity were measured throughout the study. After multiple instillations, there was no difference in corneal sensitivity between eyes over time for diclofenac (P = 0.67) or flurbiprofen (P = 0.54), with a median sensitivity of 25 mm (1.8 g/mm 2 ). After chronic dosing, there was no difference in corneal sensitivity between eyes over time for diclofenac (P = 0.82) or flurbiprofen (P = 0.56), with a median sensitivity of 35 mm (1.0 g/mm 2 ). Decreasing ambient humidity was associated with an increase in sensitivity measurements (P = 0.0001). Neither diclofenac nor flurbiprofen had an effect on corneal sensitivity after multiple-drops or twice-daily dosing for 30 days. Ambient humidity may have an effect on corneal sensitivity measurements, with a longer filament length eliciting a blink response at lower humidity. © 2016 American College of Veterinary Ophthalmologists.

Verification of the lack of correlation between age and longitudinal chromatic aberrations of the human eye from the visible to the infrared

PubMed Central

Nakajima, Masashi; Hiraoka, Takahiro; Hirohara, Yoko; Oshika, Tetsuro; Mihashi, Toshifumi

2015-01-01

Several researchers studied the longitudinal chromatic aberration (LCA) of the human eye and observed that it does not change due to age. We measured the LCA of 45 subjects’ normal right eyes at three distinct wavelengths (561, 690, and 840 nm) using a Hartmann–Shack wavefront aberrometer (HSWA) while consecutively switching between three light sources for wavefront sensing. We confirmed that the LCA of the human eye does not change due to age between 22 and 57 years. PMID:26203391

Brightness discrimination and contrast sensitivity in chronic glaucoma--a clinical study.

PubMed Central

Teoh, S L; Allan, D; Dutton, G N; Foulds, W S

1990-01-01

The visual acuity, the difference in sensitivity of the two eyes to light (brightness ratio), and contrast sensitivity were assessed in 28 patients with chronic open angle glaucoma and compared with those of 41 normal controls of similar ages and visual acuity. The results obtained were related to the results of Tübingen visual field analysis in patients with glaucoma. Twenty-four of the 28 glaucoma patients (86%) had a significant disparity in brightness ratio between the two eyes. This was found to match the frequency of visual field loss. Moreover, there was a significant relationship between the interocular differences in brightness sense and the difference in the degree of visual field loss between the two eyes. Of the glaucoma patients 39% had sum contrast sensitivities outside the normal range for age-matched normal controls. No significant correlation was found between the interocular difference in brightness sense and the visual acuity or the interocular difference in sum contrast sensitivity. It is concluded that, in the presence of a normal visual acuity, the brightness ratio test warrants evaluation as a potential screening test for chronic open angle glaucoma. PMID:2186795

Comparison of Ethnic-specific Databases in Heidelberg Retina Tomography-3 to Discriminate Between Early Glaucoma and Normal Chinese Eyes.

PubMed

Tan, Xiu Ling; Yap, Sae Cheong; Li, Xiang; Yip, Leonard W

2017-01-01

To compare the diagnostic accuracy of the 3 race-specific normative databases in Heidelberg Retina Tomography (HRT)-3, in differentiating between early glaucomatous and healthy normal Chinese eyes. 52 healthy volunteers and 25 glaucoma patients were recruited for this prospective cross-sectional study. All underwent standardized interviews, ophthalmic examination, perimetry and HRT optic disc imaging. Area under the curve (AUC) receiver operating characteristics, sensitivity and specificity were derived to assess the discriminating abilities of the 3 normative databases, for both Moorfields Regression Analysis (MRA) and Glaucoma Probability Score (GPS). A significantly higher percentage (65%) of patients were classified as "within normal limits" using the MRA-Indian database, as compared to the MRA-Caucasian and MRA-African-American databases. However, for GPS, this was observed using the African-American database. For MRA, the highest sensitivity was obtained with both Caucasian and African-American databases (68%), while the highest specificity was from the Indian database (94%). The AUC for discrimination between glaucomatous and normal eyes by MRA-Caucasian, MRA-African-American and MRA-Indian databases were 0.77 (95% CI, 0.67-0.88), 0.79 (0.69-0.89) and 0.73 (0.63-0.84) respectively. For GPS, the highest sensitivity was obtained using either Caucasian or Indian databases (68%). The highest specificity was seen with the African-American database (98%). The AUC for GPS-Caucasian, GPS-African-American and GPS-Indian databases were 0.76 (95% CI, 0.66-0.87), 0.77 (0.67-0.87) and 0.76 (0.66-0.87) respectively. Comparison of the 3 ethnic databases did not reveal significant differences to differentiate early glaucomatous from normal Chinese eyes.