Genome-wide meta-analysis of five Asian cohorts identifies PDGFRA as a susceptibility locus for corneal astigmatism

Corneal astigmatism refers to refractive abnormalities and irregularities in the curvature of the cornea, and this interferes with light being accurately focused at a single point in the eye. This ametropic condition is highly prevalent, influences visual acuity, and is a highly heritable trait. There is currently a paucity of research in the genetic etiology of corneal astigmatism. Here we report the results from five genome-wide association studies of corneal astigmatism across three Asian populations, with an initial discovery set of 4,254 Chinese and Malay individuals consisting of 2,249 cases and 2,005 controls. Replication was obtained from three surveys comprising of 2,139 Indians, an additional 929 Chinese children, and an independent 397 Chinese family trios. Variants in PDGFRA on chromosome 4q12 (lead SNP: rs7677751, allelic odds ratio?=?1.26 (95% CI: 1.16-1.36), P(meta)?=?7.87×10(-9)) were identified to be significantly associated with corneal astigmatism, exhibiting consistent effect sizes across all five cohorts. This highlights the potential role of variants in PDGFRA in the genetic etiology of corneal astigmatism across diverse Asian populations.     

Elimination of aberrations in wide-aperture magnetoelectrostatic plasma lenses

A computer model is devised for a Morozov plasma lens, in which the magnetic surfaces are equipotential surfaces of the electric field. Results are presented from numerical modeling of the focusing of ions with allowance for their longitudinal, radial, and azimuthal motions. The strengths and spatial distributions of the magnetic and electric fields are optimized. The methods for removing moment, geometric, and chromatic aberrations are analyzed. The effect of a discrete distribution of the potentials on ion focusing is modeled, and the related aberrations are examined. A computer model of an achromatic two-lens system is considered.     

LASIK for Spherical Refractive Myopia: Effect of Topographic Astigmatism (Ocular Residual Astigmatism,ORA) on Refractive Outcome

Purpose

In eyes with a preoperative plano refractive cylinder, it would appear that there is no rationale for astigmatic treatment. The aim of this retrospective, cross-sectional data analysis was to determine the amount of topographic astigmatism in refractive plano eyes that results in reduced efficacy after myopic laser in situ keratomileusis (LASIK).

Methods

This study included 267 eyes from 267 consecutive myopic patients with a refractive plano cylinder. Receiver operating characteristic analysis was used to find the cut-off values of preoperative ocular residual astigmatism (= topographic astigmatism) that can best discriminate between groups of efficacy and safety indices in preoperative plano refractive cylinder eyes.

Results

Preoperative ocular residual astigmatism (ORA) (or topographic astigmatism) of ≤0.9 diopters (D) resulted in an efficacy index of at least 0.8 statistically significantly more frequently than eyes with a preoperative ORA of >0.9 D. Eyes with a high ORA preoperatively also had a high ORA postoperatively. Regression analysis showed that each diopter of preoperative ORA reduced efficacy by 0.07.

Conclusion

A preoperative corneal astigmatism of ≥0.9 D could (partially) be taken into account in the LASIK design, even if the subjective refractive astigmatism is neutral.     

Alteration of human pancreatic secretions by pancreatic and ampullary carcinoma. A computer-aided analysis of isoelectric focusing patterns.

Human pancreatic secretions obtained from patients with pancreatic carcinoma and carcinoma of the ampulla of Vater differ significantly from those obtained from patients without pancreatic disease. Differences were also apparent between secretions from the two types of carcinoma cited above. This was shown by computer analysis of the isoelectric focusing protein patterns from 30 specimens. Average densitometric tracings ± the standard deviation were prepared by the computer for the acidic portion (pH 3–5.7) of the pH 3–10 isoelectric focusing patterns for each group of ten specimens. In this pH region 19 bands were located by the computer. The major bands had isoelectric points of 4.7, 5.0, 5.2, and 5.7.     

Distribution of Posterior Corneal Astigmatism According to Axis Orientation of Anterior Corneal Astigmatism

Purpose

To investigate the distribution of posterior corneal astigmatism in eyes with with-the-rule (WTR) and against-the-rule (ATR) anterior corneal astigmatism.

Methods

We retrospectively examined six hundred eight eyes of 608 healthy subjects (275 men and 333 women; mean age ± standard deviation, 55.3 ± 20.2 years). The magnitude and axis orientation of anterior and posterior corneal astigmatism were determined with a rotating Scheimpflug system (Pentacam HR, Oculus) when we divided the subjects into WTR and ATR anterior corneal astigmatism groups.

Results

The mean magnitudes of anterior and posterior corneal astigmatism were 1.14 ± 0.76 diopters (D), and 0.37 ± 0.19 D, respectively. We found a significant correlation between the magnitudes of anterior and posterior corneal astigmatism (Pearson correlation coefficient r = 0.4739, P<0.001). In the WTR anterior astigmatism group, we found ATR astigmatism of the posterior corneal surface in 402 eyes (96.6%). In the ATR anterior astigmatism group, we found ATR posterior corneal astigmatism in 82 eyes (73.9%). Especially in eyes with ATR anterior corneal astigmatism of 1 D or more and 1.5 D or more, ATR posterior corneal astigmatism was found in 28 eyes (59.6%) and 9 eyes (42.9%), respectively.

Conclusions

WTR anterior astigmatism and ATR posterior astigmatism were found in approximately 68% and 91% of eyes, respectively. The magnitude and the axis orientation of posterior corneal astigmatism were not constant, especially in eyes having high ATR anterior corneal astigmatism, as is often the case in patients who have undergone toric IOL implantation.     

Comparison of preoperative and postoperative astigmatism after superotemporal or superonasal clear corneal incision in phacoemulsification

The aim of this work was comparison of preoperative and postoperative astigmatism after superotemporal or superonasal clear corneal incision. Twenty eight eyes of 28 patients treated with phacoemulsification through superotemporal or superonasal 3 mm clear corneal incision were examined by kerato-refractometer preoperatively and six months postoperatively. Adequate score was assigned to each preoperative and postoperative K-value with associated axis of astigmatism to enable comparison. Wilcoxon paired samples test was used for statistical analysis. Postoperative uncorrected Snellen visual acuity was 0.5 or better in 26 patients. In one patient visual acuity was 0.3 because of diabetic maculopathy. Postoperative astigmatism was less or equal than preoperative in 18 and greater in 10 patients. There was no statistical difference between the preoperative and postoperative astigmatism (Wilcoxon paired samples test, p = 0.966) and therefore the conclusion can be made that the superotemporal or superonasal clear corneal incision has minimal effect on corneal astigmatism.     

Exploring a coarse-grained distributive strategy for finite-difference Poisson–Boltzmann calculations

We have implemented and evaluated a coarse-grained distributive method for finite-difference Poisson–Boltzmann (FDPB) calculations of large biomolecular systems. This method is based on the electrostatic focusing principle of decomposing a large fine-grid FDPB calculation into multiple independent FDPB calculations, each of which focuses on only a small and a specific portion (block) of the large fine grid. We first analyzed the impact of the focusing approximation upon the accuracy of the numerical reaction field energies and found that a reasonable relative accuracy of 10⁻³ can be achieved when the buffering space is set to be 16 grid points and the block dimension is set to be at least (1/6)³ of the fine-grid dimension, as in the one-block focusing method. The impact upon efficiency of the use of buffering space to maintain enough accuracy was also studied. It was found that an “optimal” multi-block dimension exists for a given computer hardware setup, and this dimension is more or less independent of the solute geometries. A parallel version of thedistributive focusing method was also implemented. Given the proper settings, the distributive method was able to achieve respectable parallel efficiency with tested biomolecular systems on a loosely connected computer cluster.     

准分子激光眼科治疗机中激光器控制实现

准分子激光眼科治疗机可以用来进行近视、远视、散光等屈光不正的矫正手术。其中激光器的控制为手术提供能量稳定的激光脉冲,是对手术安全性、可靠性的重要保证。本文简述了一准分子激光眼科治疗机的整体组成部分,并详细描述了激光器的控制部分:计算机与激光器的通信控制、激光发射停止控制、充换气流程控制。目前,这种准分子激光治疗机已经应用于临床,并取得了良好的效果。     

Perceptual Adaptation to the Correction of Natural Astigmatism

Background

The visual system adjusts to changes in the environment, as well as to changes within the observer, adapting continuously to maintain a match between visual coding and visual environment. We evaluated whether the perception of oriented blur is biased by the native astigmatism, and studied the time course of the after-effects following spectacle correction of astigmatism in habitually non-corrected astigmats.

Methods and Findings

We tested potential shifts of the perceptual judgments of blur orientation in 21 subjects. The psychophysical test consisted on a single interval orientation identification task in order to measure the perceived isotropic point (astigmatism level for which the image did not appear oriented to the subject) from images artificially blurred with constant blur strength (B = 1.5 D), while modifying the orientation of the blur according to the axis of natural astigmatism of the subjects. Measurements were performed after neutral (gray field) adaptation on naked eyes under full correction of low and high order aberrations. Longitudinal measurements (up to 6 months) were performed in three groups of subjects: non-astigmats and corrected and uncorrected astigmats. Uncorrected astigmats were provided with proper astigmatic correction immediately after the first session. Non-astigmats did not show significant bias in their perceived neutral point, while in astigmatic subjects the perceived neutral point was significantly biased, typically towards their axis of natural astigmatism. Previously uncorrected astigmats shifted significantly their perceived neutral point towards more isotropic images shortly (2 hours) after astigmatic correction wear, and, once stabilized, remained constant after 6 months. The shift of the perceived neutral point after correction of astigmatism was highly correlated with the amount of natural astigmatism.

Conclusions

Non-corrected astigmats appear to be naturally adapted to their astigmatism, and astigmatic correction significantly changes their perception of their neutral point, even after a brief period of adaptation.     

Effect of Orbital Decompression on Corneal Topography in Patients with Thyroid Ophthalmopathy

Objective

To evaluate changes in corneal astigmatism in patients undergoing orbital decompression surgery.

Methods

This retrospective, non randomized comparative study involved 42 eyes from 21 patients with thyroid ophthalmopathy who underwent orbital decompression surgery between September 2011 and September 2014. The 42 eyes were divided into three groups: control (9 eyes), two-wall decompression (25 eyes), and three-wall decompression (8 eyes). The control group was defined as the contralateral eyes of nine patients who underwent orbital decompression surgery in only one eye. Corneal topography (Orbscan II), Hertel exophthalmometry, and intraocular pressure were measured at 1 month before and 3 months after surgery. Corneal topographic parameters analyzed were total astigmatism (TA), steepest axis (SA), central corneal thickness (CCT), and anterior chamber depth (ACD).

Results

Exophthalmometry values and intraocular pressure decreased significantly after the decompression surgery. The change (absolute value (|x|) of the difference) in astigmatism at the 3 mm zone was significantly different between the decompression group and the controls (p = 0.025). There was also a significant change in the steepest axis at the 3 mm zone between the decompression group and the controls (p = 0.033). An analysis of relevant changes in astigmatism showed that there was a dominant tendency for incyclotorsion of the steepest axis in eyes that underwent decompression surgery. Using Astig PLOT, the mean surgically induced astigmatism (SIA) was 0.21±0.88 D with an axis of 46±22°, suggesting that decompression surgery did change the corneal shape and induced incyclotorsion of the steepest axis.

Conclusions

There was a significant change in corneal astigmatism after orbital decompression surgery and this change was sufficient to affect the optical function of the cornea. Surgeons and patients should be aware of these changes.     

Calculation and application of the anterior surface area of a model human cornea

The macroscopic anterior surface area was calculated for three models of the average human cornea. Two models, a general ellipsoid and a rotational ellipse (rotationally symmetric ellipsoid) gave a surface area of 132 mm2, while a spherical model gave 126 mm2. A general ellipsoidal model having the maximum radius horizontal (with-the-rule corneal astigmatism) has less surface area than a rotational ellipse with the same horizontal radius. For a corneal sagittal height of 2.59 mm, the surface area of an ellipsoidal cornea equals -19.2Q + 16.3R -0.476 which specifies a rotational ellipse (radius R, asphericity Q) of equal surface area. In a cornea with the maximum radius vertical (against-the-rule corneal astigmatism), the ellipsoid has slightly more surface area than a rotational ellipse with the same horizontal radius of curvature. For a given horizontal radius of curvature, the sphere has the lowest surface area. For a corneal sagittal height s of 2.59 mm, the sphere underestimates by 8% the surface area of a rotational ellipse with asphericity -0.5. The anterior corneal surface area of a rotational ellipse model, radius R, asphericity Q is given by 2 pi Rs- 19.2Q. In all three models, the surface area increases with horizontal radius of curvature. In the rotational ellipse model, the rate of increase (slope) is independent of asphericity, and the slope found in with-the-rule astigmatism is less than the slope found with against-the-rule astigmatism. The calculated surface area predicts a precorneal tear volume of 0.86 microliter for a 6.5 micron tear thickness. The apparent, or plane projected are of an epithelial lesion underestimates the curved surface area with a percentage error that increases rapidly with lesion diameter. For a 12 mm diameter lesion on a rotational ellipse model, the apparent area underestimates the surface area by 18%. The average posterior corneal surface in human is not spherical but imitates the anterior surface, and has an area of 137 mm2 or 3.8% greater than the anterior area.     

Radial averages of astigmatic TEM images

The Contrast Transfer Function (CTF) of an image, which modulates images taken from a Transmission Electron Microscope (TEM), is usually determined from the radial average of the power spectrum of the image (Frank, J., Three-dimensional Electron Microscopy of Macromolecular Assemblies, Oxford University Press, Oxford, 2006). The CTF is primarily defined by the defocus. If the defocus estimate is accurate enough then it is possible to demodulate the image, which is popularly known as the CTF correction. However, it is known that the radial average is somewhat attenuated if the image is astigmatic (see Fernando, K.V., Fuller, S.D., 2007. Determination of astigmatism in TEM images. Journal of Structural Biology 157, 189-200) but this distortion due to astigmatism has not been fully studied or understood up to now. We have discovered the exact mathematical relationship between the radial averages of TEM images with and without astigmatism. This relationship is determined by a zeroth order Bessel function of the first kind and hence we can exactly quantify this distortion in the radial averages of signal and power spectra of astigmatic images. The argument to this Bessel function is similar to an aberration function (without the spherical aberration term) except that the defocus parameter is replaced by the differences of the defoci in the major and minor axes of astigmatism. The ill effects due this Bessel function are twofold. Since the zeroth order Bessel function is a decaying oscillatory function, it introduces additional zeros to the radial average and it also attenuates the CTF signal in the radial averages. Using our analysis, it is possible to simulate the effects of astigmatism in radial averages by imposing Bessel functions on idealized radial averages of images which are not astigmatic. We validate our theory using astigmatic TEM images.     

Calculation and optimization of plasma-optic focusing devices

(i) The focusing of an ion beam by a Morozov lens formed by a current ring in a plasma is calculated using an exact expression for the magnetic field and taking into account the nonparaxial character of the focused beam. The possible ways of optimizing such a lens are considered. (ii) Different versions of extended plasmaoptic devices in which spherical aberrations are minimized are analyzed. It is proposed to optimize extended plasma-optic devices by changing the magnetic field from the entrance end to the exit end of the solenoid in such a way that the boundary magnetic surface always coincides with the boundary surface of the focused beam. It is shown that, under the same conditions, the focusing power of the optimized devices is one to two orders of magnitude higher than that of traditional thin plasma lenses. (iii) The problem of creating a magnetic field whose strength is optimized as a function of the longitudinal coordinate is solved by the Tikhonov regularization method. (iv) An extended plasma-optic device with an optimized solenoid for focusing 1-MeV ion beams is calculated, and the ion trajectories in the device are traced. (v) It is proved expedient to develop special-purpose computer codes aimed at modeling and optimizing the existing and planned experimental plasma-optic focusing devices.     

Comparison of Astigmatic Correction after Femtosecond Lenticule Extraction and Small-Incision Lenticule Extraction for Myopic Astigmatism

Purpose

To compare postoperative astigmatic correction between femtosecond lenticule extraction (FLEx) and small-incision lenticule extraction (SMILE) in eyes with myopic astigmatism.

Methods

We examined 26 eyes of 26 patients undergoing FLEx and 26 eyes of 26 patients undergoing SMILE to correct myopic astigmatism (manifest astigmatism of 1 diopter (D) or more). Visual acuity, cylindrical refraction, the predictability of the astigmatic correction, and the astigmatic vector components using Alpin’s method, were compared between the two groups 3 months postoperatively.

Results

We found no statistically significant difference in manifest cylindrical refraction (p=0.74) or in the percentage of eyes within ± 0.50 D of their refraction (p=0.47) after the two surgical procedures. Moreover, no statistically significant difference was detected between the groups in astigmatic vector components, namely, surgically induced astigmatism (0.80), target induced astigmatism (p=0.87), astigmatic correction index (p=0.77), angle of error (p=0.24), difference vector (p=0.76), index of success (p=0.91), flattening effect (p=0.79), and flattening index (p=0.84).

Conclusions

Both FLEx and SMILE procedures are essentially equivalent in correcting myopic astigmatism using vector analysis, suggesting that the lifting or non-lifting of the flap does not significantly affect astigmatic outcomes after these surgical procedures.     

An automated system for genome analysis to support microbial whole-genome shotgun sequencing

We developed a semi-automated genome analysis system called GAMBLER in order to support the current whole-genome sequencing project focusing on alkaliphilic Bacillus halodurans C-125. GAMBLER was designed to reduce the human intervention required and to reduce the complications in annotating thousands of ORFs in the microbial genome. GAMBLER automates three major routines: analyzing assembly results provided by genome assembler software, assigning ORFs, and homology searching. GAMBLER is equipped with an interface for convenience of annotation. All processes and options are manipulatable through a WWW browser that enables scientists to share their genome analysis results without choosing computer platforms.     

Keratometry device for surgical support

Background  

High astigmatisms are usually induced during corneal suturing subsequent to tissue transplantation or any other surgery which involves corneal suturing. One of the reasons is that the procedure is intimately dependent on the surgeon's skill for suturing identical stitches. In order to evaluate the influence of the irregularity on suturing for the residual astigmatism, a prototype for ophthalmic surgical support has been developed. The final intention of this prototype is to be an evaluation tool for guided suture and as an outcome diminish the postoperative astigmatism.     

Digestion of Algal Biomass for Electricity Generation in Microbial Fuel Cells

We developed a semi-automated genome analysis system called GAMBLER in order to support the current whole-genome sequencing project focusing on alkaliphilic Bacillus halodurans C-125. GAMBLER was designed to reduce the human intervention required and to reduce the complications in annotating thousands of ORFs in the microbial genome. GAMBLER automates three major routines: analyzing assembly results provided by genome assembler software, assigning ORFs, and homology searching. GAMBLER is equipped with an interface for convenience of annotation. All processes and options are manipulatable through a WWW browser that enables scientists to share their genome analysis results without choosing computer platforms.     

Comparison of Anterior Segment Biometric Measurements between Pentacam HR and IOLMaster in Normal and High Myopic Eyes

Purpose

To compare the anterior chamber depth (ACD), keratometry (K) and astigmatism measurements taken by IOLMaster and Pentacam HR in normal and high myopic (HM) eyes.

Design

A prospective observational case series.

Methods

Sixty-six normal eyes and 59 HM eyes underwent ACD, keratometry and astigmatism measurements with both devices. Axial length (AL) was measured on IOLMaster. The interdevice agreement was evaluated using the Bland-Altman analysis and paired t-test. The correlations between age and AL & ACD were analyzed. Vector analysis was used to compare astigmatism measurements.

Results

The ACD from IOLMaster and Pentacam HR was different for the normal group (P = 0.003) but not for the HM group (P = 0.280). IOLMaster demonstrated higher steep K and mean K values than Pentacam HR for both normal and HM groups (P<0.001 for all). IOLMaster also have higher flat K values for the HM groups (P<0.001) but were statistically equivalent with Pentacam HR for the normal group (P = 0.119) IOLMaster and Pentacam HR were different in astigmatism measurements for the normal group but were statistically equivalent for the HM group. For the normal group, age was negatively correlated with AL, IOLMaster ACD and Pentacam HR ACD (r = -0.395, P = 0.001; r = -0.715, P < 0.001; r = -0.643, P < 0.001). For the HM group, age was positively correlated with AL but negatively correlated with IOLMaster ACD and Pentacam HR ACD (r = 0.377, P = 0.003; r = -0.392, P = 0.002; r = -0.616, P < 0.001).

Conclusions

The IOLMaster and Pentacam HR have significant difference in corneal power measurements for both normal and HM groups. The two instruments also differ in ACD and astigmatism measurement for the normal group. Therefore, a single instrument is recommended for studying longitudinal changes in anterior segment biometric measurements. Age should be considered as an influencing factor for both AL and ACD values in the normal and HM group.     

Improved detection limits in an organic mass spectrometer using a combination of matrix free FAB and photodiode array detection

Scanning mass spectrometers suffer from the disadvantage of monitoring only one mass at any particular time in contrast to mass spectrographs which allow the simultaneous detection of an extended mass range. Historically such mass spectra were recorded by directing the ion beam onto a photographic plate which was subsequently developed and interpreted. The introduction of electronic devices such as the photodiode array enabled the development of imaging detectors capable of real time readout, so that a range of masses can be detected and rapidly processed using a computer system. This work uses such a detector in combination with a double focusing MS50RF mass spectrometer for the parallel detection of a limited mass range.     

Mathematical model for transient isoelectric focusing of simple ampholytes

A mathematical model describing transient processes in isoelectric focusing (IEF) of L biprotic ampholytes is presented. The model is a generalization of our previous research on steady slate in IEF and consists of L nonlinear partial differential equations coupled with 2L+2 algebraic equations. Constraints imposed by the mode of operation, viz., constant current. voltage or power, are described. Due to the nonlinearity of the equations, analysis of the model requires computer simulation. Model equations suitable for computer implementation are derived.