Corneal changes following near work in myopic anisometropia

Purpose: To examine the symmetry of corneal changes following near work in the fellow eyes of non-amblyopic myopic anisometropes. Methods: Thirty-four non-amblyopic, myopic anisometropes (minimum 1 D spherical equivalent anisometropia) had corneal topography measured before and after a controlled near work task. Subjects were positioned in a headrest to minimise head movements and read continuous text on a computer monitor for 10 minutes at an angle of 25 degrees downward gaze and an accommodation demand of 2.5 D. Measures of the morphology of the palpebral aperture during primary and downward gaze were also obtained. Results: The more and less myopic eyes exhibited a high degree of interocular symmetry for measures of palpebral aperture morphology during both primary and downward gaze. Following the near work task, fellow eyes also displayed a symmetrical change in superior corneal topography (hyperopic defocus) which correlated with the position of the upper eyelid during downward gaze. Greater changes in the spherical corneal power vector (M) following reading were associated with narrower palpebral aperture during downward gaze (p = 0.07 for more myopic and p = 0.03 for less myopic eyes). A significantly greater change in J0 (an increase in against the rule astigmatism) was observed in the more myopic eyes (-0.04 ± 0.04 D) compared to the less myopic eyes (-0.02 ± 0.06 D) over a 6 mm corneal diameter (p = 0.01). Conclusions: Changes in corneal topography following near work are highly symmetrical between the fellow eyes of myopic anisometropes due to the interocular symmetry of the palpebral aperture. However, the more myopic eye exhibits changes in corneal astigmatism of greater magnitude compared to the less myopic eye.

Effect of age on components of peripheral ocular aberrations

Purpose: To investigate the effect of age on the contributions of the anterior cornea and internal components to ocular aberrations in the peripheral visual field. Methods: Ocular aberrations were measured in 10 young emmetropes and 7 older emmetropes using a modified commercial Hartmann-Shack aberrometer across 42° x 32° of central visual field. Anterior corneal aberrations were estimated from anterior corneal topography using theoretical ray-tracing. Internal aberrations were calculated by subtracting anterior corneal aberrations from ocular aberrations. Results: Anterior corneal aberrations of young subjects were reasonably compensated by the internal aberrations, except for astigmatism for which the internal contribution was small out to the 21° field limit. The internal coma and spherical aberration of the older subjects were considerably smaller in magnitude than those of the young subjects such that the compensation for anterior corneal aberrations was poorer. This can be explained by age-related changes in the lens shape and refractive index distribution. Conclusion: oss of balance between anterior cornea and internal components of higher order aberrations with increasing age, found previously for on-axis vision, applies also to the peripheral visual field.

Dry powder inhaler formulations : effect of carrier size on the drug dispersion

Background: The size of the carrier influences drug aerosolization from a dry powder inhaler (DPI) formulation. Lactose particles with irregular shape and rough surface in a variety of sizes are additionally used as carriers; however, contradictory reports exist regarding the effect of carrier size on the dispersion of drug. We examined the influence of the spherical particle size of the biodegradable polylactide-co-glycolide (PLGA) carrier on the aerosolization of a model drug, salbutamol sulphate (SS). Methods: Four different sizes (20-150 µm) of polymer carriers were fabricated using solvent evaporation technique and the dispersion of SS from these carriers was measured by a Twin Stage Impinger (TSI). The size and morphological properties of polymer carriers were determined by laser diffraction and SEM, respectively. Results: The FPF was found to increase from 5.6% to 21.3% with increasing carrier sizeup to150 µm. Conclusions: The aerosolization of drug increased linearly with the size of polymer carriers. For a fixed mass of drug particles in a formulation, the mass of drug particles per unit area of carriers is higher in formulations containing the larger carriers, which leads to an increase in the dispersion of drug due to the increased mechanical forces occurred between the carriers and the device walls.

Structure of the immature retroviral capsid at 8 Å resolution by cryo-electron microscopy

The assembly of retroviruses such as HIV-1 is driven by oligomerization of their major structural protein, Gag. Gag is a multidomain polyprotein including three conserved folded domains: MA (matrix), CA (capsid) and NC (nucleocapsid)(1). Assembly of an infectious virion proceeds in two stages(2). In the first stage, Gag oligomerization into a hexameric protein lattice leads to the formation of an incomplete, roughly spherical protein shell that buds through the plasma membrane of the infected cell to release an enveloped immature virus particle. In the second stage, cleavage of Gag by the viral protease leads to rearrangement of the particle interior, converting the non-infectious immature virus particle into a mature infectious virion. The immature Gag shell acts as the pivotal intermediate in assembly and is a potential target for anti-retroviral drugs both in inhibiting virus assembly and in disrupting virus maturation(3). However, detailed structural information on the immature Gag shell has not previously been available. For this reason it is unclear what protein conformations and interfaces mediate the interactions between domains and therefore the assembly of retrovirus particles, and what structural transitions are associated with retrovirus maturation. Here we solve the structure of the immature retroviral Gag shell from Mason-Pfizer monkey virus by combining cryo-electron microscopy and tomography. The 8-angstrom resolution structure permits the derivation of a pseudo-atomic model of CA in the immature retrovirus, which defines the protein interfaces mediating retrovirus assembly. We show that transition of an immature retrovirus into its mature infectious form involves marked rotations and translations of CA domains, that the roles of the amino-terminal and carboxy-terminal domains of CA in assembling the immature and mature hexameric lattices are exchanged, and that the CA interactions that stabilize the immature and mature viruses are almost completely distinct.

Analysis of higher-order aberrations in a large clinical population

Purpose: To use a large wavefront database of a clinical population to investigate relationships between refractions and higher order aberrations and between aberrations of right and left eyes. Methods: Third and fourth-order aberration coefficients and higher-order root-mean-squared aberrations (HO RMS), scaled to a pupil size of 4.5 mm diameter, were analysed in a population of about 24,000 patients from Carl Zeiss Vision's European wavefront database. Correlations were determined between the aberrations and the variables of refraction, near addition and cylinder. Results: Most aberration coefficients were significantly dependent upon these variables, but the proportions of aberrations that could be explained by these factors were less than 2% except for spherical aberration (12%), horizontal coma (9%) and HO RMS (7%). Near addition was the major contributor for horizontal coma (8.5% out of 9.5%) and spherical equivalent was the major contributor for spherical aberration (7.7% out of 11.6%). Interocular correlations were highly significant for all aberration coefficients, varying between 0.16 and 0.81. Anisometropia was a variable of significance for three aberrations (vertical coma, secondary astigmatism and tetrafoil), but little importance can be placed on this because of the small proportions of aberrations that can be explained by refraction (all less than 1.0 %). Conclusions: Most third- and fourth-order aberration coefficients were significantly dependent upon spherical equivalent, near addition and cylinder, but only horizontal coma (9%) and spherical aberration (12%) showed dependencies of greater than 2%. Interocular correlations were highly significant for all aberration coefficients, but anisometropia had little influence on aberration coefficients.

Retinal and choroidal thickness in myopic anisometropia

Purpose: To compare the retinal thickness (RT) and choroidal thickness (ChT) between the fellow eyes of non-amblyopic myopic anisometropes. Methods: The eyes of 22 non-amblyopic myopic anisometropes (1 D spherical equivalent refraction [SER] anisometropia) were examined using spectral domain optical coherence tomography (SD-OCT). Customised software was used to register, align and average multiple foveal OCT B-Scan images from each subject in order to enhance image quality. Two independent masked observers manually determined the RT and ChT from each SD-OCT image up to 2.5 mm nasal and temporal to the fovea. Axial length (AXL) was measured using optical low coherence biometry during relaxed accommodation. Results: The mean SER anisometropia was 1.74 ± 0.95 D and the mean interocular AXL difference was 0.58 ± 0.41 mm. There was no significant difference in foveal RT between the fellow eyes (P > 0.05). Mean subfoveal ChT was significantly thinner in the more myopic eye (252 ± 46 μm compared to the fellow, less myopic eye (286 ± 58 μm) (P < 0.001). There was a moderate correlation between the interocular difference in subfoveal ChT and the interocular difference in AXL (r = -0.50, P < 0.01). Asian anisometropes displayed more regionally symmetrical (nasal-temporal)interocular differences in ChT profile compared to Caucasians. Conclusions: RT was similar between the fellow eyes of myopic anisometropes; however, the subfoveal choroid was significantly thinner in the more myopic (longer) eye of this anisometropic cohort. The interocular asymmetry in ChT correlated with the interocular difference in AXL.

Conserved and variable features of gag structure and arrangement in immature retrovirus particles

The assembly of retroviruses is driven by oligomerization of the Gag polyprotein. We have used cryo-electron tomography together with subtomogram averaging to describe the three-dimensional structure of in vitro-assembled Gag particles from human immunodeficiency virus, Mason-Pfizer monkey virus, and Rous sarcoma virus. These represent three different retroviral genera: the lentiviruses, betaretroviruses and alpharetroviruses. Comparison of the three structures reveals the features of the supramolecular organization of Gag that are conserved between genera and therefore reflect general principles of Gag-Gag interactions and the features that are specific to certain genera. All three Gag proteins assemble to form approximately spherical hexameric lattices with irregular defects. In all three genera, the N-terminal domain of CA is arranged in hexameric rings around large holes. Where the rings meet, 2-fold densities, assigned to the C-terminal domain of CA, extend between adjacent rings, and link together at the 6-fold symmetry axis with a density, which extends toward the center of the particle into the nucleic acid layer. Although this general arrangement is conserved, differences can be seen throughout the CA and spacer peptide regions. These differences can be related to sequence differences among the genera. We conclude that the arrangement of the structural domains of CA is well conserved across genera, whereas the relationship between CA, the spacer peptide region, and the nucleic acid is more specific to each genus.

Methods to estimate the size and shape of the unaccommodated crystalline lens in vivo

Purpose. The purpose of this article was to present methods capable of estimating the size and shape of the human eye lens without resorting to phakometry or magnetic resonance imaging (MRI). Methods. Previously published biometry and phakometry data of 66 emmetropic eyes of 66 subjects (age range [18, 63] years, spherical equivalent range [−0.75, +0.75] D) were used to define multiple linear regressions for the radii of curvature and thickness of the lens, from which the lens refractive index could be derived. MRI biometry was also available for a subset of 30 subjects, from which regressions could be determined for the vertex radii of curvature, conic constants, equatorial diameter, volume, and surface area. All regressions were compared with the phakometry and MRI data; the radii of curvature regressions were also compared with a method proposed by Bennett and Royston et al. Results. The regressions were in good agreement with the original measurements. This was especially the case for the regressions of lens thickness, volume, and surface area, which each had an R2 > 0.6. The regression for the posterior radius of curvature had an R2 < 0.2, making this regression unreliable. For all other regressions we found 0.25 < R2 < 0.6. The Bennett-Royston method also produced a good estimation of the radii of curvature, provided its parameters were adjusted appropriately. Conclusions. The regressions presented in this article offer a valuable alternative in case no measured lens biometry values are available; however care must be taken for possible outliers.

Composition and morphology of particle emissions from in-use aircraft during takeoff and landing

In order to provide realistic data for air pollution inventories and source apportionment at airports, the morphology and composition of ultrafine particles (UFP) in aircraft engine exhaust were measured and characterized. For this purpose, two independent measurement techniques were employed to collect emissions during normal takeoff and landing operations at Brisbane Airport, Australia. PM1 emissions in the airfield were collected on filters and analyzed using the particle-induced X-ray emission (PIXE) technique. Morphological and compositional analyses of individual ultrafine particles in aircraft plumes were performed on silicon nitride membrane grids using transmission electron microscopy (TEM) combined with energy-dispersive X-ray microanalysis (EDX). TEM results showed that the deposited particles were in the range of 5 to 100 nm in diameter, had semisolid spherical shapes and were dominant in the nucleation mode (18 – 20 nm). The EDX analysis showed the main elements in the nucleation particles were C, O, S and Cl. The PIXE analysis of the airfield samples was generally in agreement with the EDX in detecting S, Cl, K, Fe and Si in the particles. The results of this study provide important scientific information on the toxicity of aircraft exhaust and their impact on local air quality.

Calculation of dose kernels for radiotherapy applications using the GEANT 4 Monte Carlo toolkit

Dose kernels may be used to calculate dose distributions in radiotherapy (as described by Ahnesjo et al., 1999). Their calculation requires use of Monte Carlo methods, usually by forcing interactions to occur at a point. The Geant4 Monte Carlo toolkit provides a capability to force interactions to occur in a particular volume. We have modified this capability and created a Geant4 application to calculate dose kernels in cartesian, cylindrical, and spherical scoring systems. The simulation considers monoenergetic photons incident at the origin of a 3 m x 3 x 9 3 m water volume. Photons interact via compton, photo-electric, pair production, and rayleigh scattering. By default, Geant4 models photon interactions by sampling a physical interaction length (PIL) for each process. The process returning the smallest PIL is then considered to occur. In order to force the interaction to occur within a given length, L_FIL, we scale each PIL according to the formula: PIL_forced = L_FIL 9 (1 - exp(-PIL/PILo)) where PILo is a constant. This ensures that the process occurs within L_FIL, whilst correctly modelling the relative probability of each process. Dose kernels were produced for an incident photon energy of 0.1, 1.0, and 10.0 MeV. In order to benchmark the code, dose kernels were also calculated using the EGSnrc Edknrc user code. Identical scoring systems were used; namely, the collapsed cone approach of the Edknrc code. Relative dose difference images were then produced. Preliminary results demonstrate the ability of the Geant4 application to reproduce the shape of the dose kernels; median relative dose differences of 12.6, 5.75, and 12.6 % were found for an incident photon energy of 0.1, 1.0, and 10.0 MeV respectively.

Study of structural changes of pumpkin tissue before and after mechanical loading

The texture of agricultural crops changes during harvesting, post harvesting and processing stages due to different loading processes. There are different source of loading that deform agricultural crop tissues and these include impact, compression, and tension. Scanning Electron Microscope (SEM) method is a common way of analysing cellular changes of materials before and after these loading operations. This paper examines the structural changes of pumpkin peel and flesh tissues under mechanical loading. Compression and indentation tests were performed on peel and flesh samples. Samples structure were then fixed and dehydrated in order to capture the cellular changes under SEM. The results were compared with the images of normal peel and flesh tissues. The findings suggest that normal flesh tissue had bigger size cells, while the cellular arrangement of peel was smaller. Structural damage was clearly observed in tissue structure after compression and indentation. However, the damages that resulted from the flat end indenter was much more severe than that from the spherical end indenter and compression test. An integrated deformed tissue layer was observed in compressed tissue, while the indentation tests shaped a deformed area under the indenter and left the rest of the tissue unharmed. There was an obvious broken layer of cells on the walls of the hole after the flat end indentations, whereas the spherical indenter created a squashed layer all around the hole. Furthermore, the influence of loading was lower on peel samples in comparison with the flesh samples. The experiments have shown that the rate of damage on tissue under constant rate of loading is highly dependent on the shape of equipment. This fact and observed structural changes after loading underline the significance of deigning post harvesting equipments to reduce the rate of damage on agricultural crop tissues.

Image-based visual navigation for mobile robots

We introduce a new image-based visual navigation algorithm that allows the Cartesian velocity of a robot to be defined with respect to a set of visually observed features corresponding to previously unseen and unmapped world points. The technique is well suited to mobile robot tasks such as moving along a road or flying over the ground. We describe the algorithm in general form and present detailed simulation results for an aerial robot scenario using a spherical camera and a wide angle perspective camera, and present experimental results for a mobile ground robot.

Diurnal variation of ocular biometrics under natural and defocused conditions

It is well known that a broad range of ocular anatomical and physiological parameters undergo significant diurnal variation. However, the natural diurnal variations that occur in the length of the human eye (axial length) and their underlying causes have been less well studied. Improvements in optical methods for the measurement of ocular biometrics now allow more precise and comprehensive measurements of axial length to be performed than has previously been possible. Research from animal models also suggests a link between diurnal axial length variations and longer term myopic eye growth, and that retinal image defocus can disrupt these diurnal rhythms in axial length. This research programme has examined the diurnal variations in axial length in young normal eyes, the contributing components and the influence of optical stimuli on these changes. In the first experiment, the normal pattern and consistency of the diurnal variations in axial length were examined at 10 different times (5 measurements each day, at ~ 3-hour intervals from ~ 9 am to ~ 9 pm) over 2 consecutive days on 30 young adult subjects (15 myopes, 15 emmetropes). Additionally, variations in a range of other ocular biometric measurements such as choroidal thickness, intraocular pressure, and other ocular biometrics were also explored as potential factors that may be associated with the observed variations in axial length. To investigate the potential influence of refractive error on diurnal axial length variations, the differences in the magnitude and pattern of diurnal variations in axial length between the myopic and emmetropic subjects were examined. Axial length underwent significant diurnal variation that was consistently observed over the 2 consecutive days of measurements, with the longest axial length typically occurring during the day, and the shortest at night. Significant diurnal variations were also observed in choroidal thickness, IOP and other ocular biometrics (such as central corneal thickness, anterior chamber depth and vitreous chamber depth) of the eye. Diurnal variations in vitreous chamber depth, IOP (positive associations) and choroidal thickness (negative association) were all significantly correlated with the diurnal changes in axial length. Choroidal thickness was found to fluctuate approximately in antiphase to the axial length changes, with the average timing of the longest axial length coinciding with the thinnest choroid and vice versa. There were no significant differences in the ocular diurnal variations associated with refractive error. Given that the diurnal changes in axial length could be associated with the changes in the eye’s optical quality, whether the optical quality of the eye also undergoes diurnal variation in the same cohort of young adult myopes and emmetropes over 2 consecutive days was also examined. Significant diurnal variations were observed only in the best sphere refraction (power vector M) and in the spherical aberration of the eye over two consecutive days of testing. The changes in the eyes lower and higher order ocular optics were not significantly associated with the diurnal variations in axial length and the other measured ocular biometric parameters. No significant differences were observed in the magnitude and timing of diurnal variations in lower-order and higher-order optics associated with refractive error. Since the small natural fluctuations in the eye’s optical quality did not appear to be sufficient to influence the natural diurnal fluctuations in ocular biometric parameters, in the next experiment, the influence of monocular myopic defocus (+1.50 DS) upon the normal diurnal variations in axial length and choroidal thickness of young adult emmetropic human subjects (n=13) imposed over a 12 hour period was examined. A series of axial length and choroidal thickness measurements (collected at ~3 hourly intervals, with the first measurement at ~9 am and the final measurement at ~9 pm) were obtained over three consecutive days. The natural diurnal rhythms (Day 1, no defocus), diurnal rhythms with monocular myopic defocus (Day 2, +1.50 DS spectacle lens over the right eye), and the recovery from any defocus induced changes (Day 3, no defocus) were examined. Significant diurnal variations over the course of the day were observed in both axial length and choroidal thickness on each of the three measurement days. The introduction of monocular myopic defocus led to significant reductions in the mean amplitude of diurnal change, and phase shifts in the peak timing of the diurnal rhythms in axial length and choroidal thickness. These defocus induced changes were found to be transient in nature and returned to normal the day following removal of the defocus. To further investigate the influence of optical stimuli on human diurnal rhythms, in the final experiment, the influence of monocular hyperopic defocus on the normal diurnal rhythms in axial length and choroidal thickness was examined in young adult emmetropic subjects (n=15). Similar to the previous experiment, the natural diurnal rhythms (Day 1, no defocus), diurnal rhythms with monocular hyperopic defocus (Day 2, -2.00 DS spectacle lens over the right eye), and the recovery from any defocus induced changes (Day 3, no defocus) were examined over three consecutive days. Both axial length and choroidal thickness underwent significant diurnal variations on each of the three days. The introduction of monocular hyperopic defocus resulted in a significant increase in the amplitude of diurnal change, but no change in the peak timing of diurnal rhythms in both parameters. The ocular changes associated with hyperopic defocus returned to normal, the day following removal of the defocus. This research has shown that axial length undergoes significant diurnal variation in young adult human eyes, and has shown that the natural diurnal variations in choroidal thickness and IOP are significantly associated, and may underlie these diurnal fluctuations in axial length. This work also demonstrated for the first time that exposing young human eyes to monocular myopic and hyperopic defocus leads to a significant disruption in the normal diurnal rhythms of axial length and choroidal thickness. These changes in axial length with defocus may reflect underlying mechanisms in the human eye that are involved in the regulation of longer term eye growth.

The association between time spent outdoors and myopia using a novel biomarker of outdoor light exposure

PURPOSE: We sought to determine whether conjunctival ultraviolet autofluorescence (UVAF), a biomarker of outdoor light exposure, is associated with myopia. METHODS: We performed a cross-sectional study on Norfolk Island and recruited individuals aged ≥ 15 years. Participants completed a sun-exposure questionnaire and underwent non-cycloplegic autorefraction. Conjunctival UVAF used a specially adapted electronic flash system fitted with UV-transmission filters (transmittance range 300-400 nm, peak 365 nm) as the excitation source. Temporal and nasal conjunctival UVAF was measured in both eyes using computerized photographic analysis with the sum referred to as "total UVAF." RESULTS: In 636 participants, prevalence of myopia decreased with an increasing quartile of total UVAF (P(trend) = 0.002). Median total UVAF was lower in subjects with myopia (spherical equivalent [SE] ≤ -1.0 diopter [D]) than participants without myopia: 16.6 mm(2) versus 28.6 mm(2), P = 0.001. In the multivariable model that adjusted for age, sex, smoking, cataract, height and weight, UVAF was independently associated with myopia (SE ≤ -1.0 D): odds ratio (OR) for total UVAF (per 10 mm(2)) was 0.81, 95% confidence interval (CI) 0.69 to 0.94, P = 0.007. UVAF was also significantly associated with myopia when analysis was restricted to subjects <50 years, and in moderate-severe myopia (SE ≤ -3.0 D). Prevalence of myopia decreased with increasing time outdoors (P(trend) = 0.03), but time outdoors was not associated with myopia on multivariable analysis. CONCLUSIONS: Study authors identified a protective association between increasing UVAF and myopia. The protective association of higher UVAF against myopia was stronger than that of increased levels of time spent outdoors as measured by this study's questionnaire. Future studies should investigate the association between UVAF and incident myopia, and its relationship to myopic progression.

Prevalence and predictors of refractive error in a genetically isolated population : the Norfolk Island Eye Study

BACKGROUND: We aimed to determine the prevalence and associations of refractive error on Norfolk Island. DESIGN: Population-based study on Norfolk Island, South Pacific. PARTICIPANTS: All permanent residents on Norfolk Island aged ≥ 15 years were invited to participate. METHODS: Patients underwent non-cycloplegic autorefraction, slit-lamp biomicroscope examination and biometry assessment. Only phakic eyes were analysed. MAIN OUTCOME MEASURES: Prevalence and multivariate associations of refractive error and myopia. RESULTS: There were 677 people (645 right phakic eyes, 648 left phakic eyes) aged ≥ 15 years were included in this study. Mean age of participants was 51.1 (standard deviation 15.7; range 15-81). Three hundred and seventy-six people (55.5%) were female. Adjusted to the 2006 Norfolk Island population, prevalence estimates of refractive error were as follows: myopia (mean spherical equivalent ≥ -1.0 D) 10.1%, hypermetropia (mean spherical equivalent ≥ 1.0 D) 36.6%, and astigmatism 17.7%. Significant independent predictors of myopia in the multivariate model were lower age (P < 0.001), longer axial length (P < 0.001), shallower anterior chamber depth (P = 0.031) and increased corneal curvature (P < 0.001). Significant independent predictors of refractive error were increasing age (P < 0.001), male gender (P = 0.009), Pitcairn ancestry (P = 0.041), cataract (P < 0.001), longer axial length (P < 0.001) and decreased corneal curvature (P < 0.001). CONCLUSIONS: The prevalence of myopia on Norfolk Island is lower than on mainland Australia, and the Norfolk Island population demonstrates ethnic differences in the prevalence estimates. Given the significant associations between refractive error and several ocular biometry characteristics, Norfolk Island may be a useful population in which to find the genetic basis of refractive error.