Diurnal variation of anterior scleral and conjunctival thickness

Purpose To examine whether anterior scleral and conjunctival thickness undergoes significant diurnal variation over a 24-hour period. Methods Nineteen healthy young adults (mean age 22 ± 2 years) with minimal refractive error (mean spherical equivalent refraction -0.08 ± 0.39 D), had measures of anterior scleral and conjunctival thickness collected using anterior segment optical coherence tomography (AS-OCT) at seven measurement sessions over a 24-hour period. The thickness of the temporal anterior sclera and conjunctiva were determined at 6 locations (each separated by 0.5 mm) at varying distances from the scleral spur for each subject at each measurement session. Results Both the anterior sclera and conjunctiva were found to undergo significant diurnal variations in thickness over a 24-hour period (both p <0.01). The sclera and conjunctiva exhibited a similar pattern of diurnal change, with a small magnitude thinning observed close to midday, and a larger magnitude thickening observed in the early morning immediately after waking. The amplitude of diurnal thickness change was larger in the conjunctiva (mean amplitude 69 ± 29 μm) compared to the sclera (21 ± 8 μm). The conjunctiva exhibited its smallest magnitude of change at the scleral spur location (mean amplitude 56 ± 17 μm) whereas the sclera exhibited its largest magnitude of change at this location (52 ± 21 μm). Conclusions This study provides the first evidence of diurnal variations occurring in the thickness of the anterior sclera and conjunctiva. Studies requiring precise measures of these anatomical layers should therefore take time of day into consideration. The majority of the observed changes occurred in the early morning immediately after waking and were of larger magnitude in the conjunctiva compared to the sclera. Thickness changes at other times of the day were of smaller magnitude and generally not statistically significant.

Axial length charges during accommodation in myopes and emmetropes

Purpose: To investigate the influence of accommodation upon axial length (and a comprehensive range of ocular biometric parameters), in populations of young adult myopic and emmetropic subjects. Methods: Forty young adult subjects had ocular biometry measured utilizing a non-contact optical biometer (Lenstar LS 900) based upon the principle of optical low coherence reflectometry, under three different accommodation demands (0 D, 3 D and 6 D). Subjects were classified as emmetropes (n=19) or myopes (n=21) based upon their spherical equivalent refraction (mean emmetropic refraction -0.05 ± 0.27DS and mean myopic refraction -1.82 ± 0.84 DS). Results: Axial length changed significantly with accommodation, with a mean increase of 11.9 ± 12.3 µm and 24.1 ± 22.7 µm for the 3 D and 6 D accommodation stimuli respectively. A significant axial elongation associated with accommodation was still evident even following correction of the axial length data for potential error due to lens thickness change. The mean ‘corrected’ increase in axial length was 5.2 ± 11.2 µm, and 7.4 ± 18.9 µm for the 3 D and 6 D stimuli respectively. There was no significant difference between the myopic and emmetropic populations in terms of the magnitude of change in axial length with accommodation, regardless of whether the data were corrected or not. A number of other ocular biometric parameters, such as anterior chamber depth, lens thickness and vitreous chamber depth also exhibited significant change with accommodation. The myopic and emmetropic populations also exhibited no significant difference in the magnitude of change in these parameters with accommodation. Conclusions: The eye undergoes a significant axial elongation associated with a brief period of accommodation, and the magnitude of this change in eye length increases for larger accommodation demands, however there is no significant difference in the magnitude of eye elongation in myopic and emmetropic subjects.

Using optical coherence tomography to assess corneoscleral morphology after soft contact lens wear

Purpose. To evaluate the use of optical coherence tomography (OCT) to assess the effect of different soft contact lenses on corneoscleral morphology. Methods. Ten subjects had anterior segment OCT B-scans taken in the morning and again after six hours of soft contact lens wear. For each subject, three different contact lenses were used in the right eye on non-consecutive days, including a hydrogel sphere, a silicone hydrogel sphere and a silicone hydrogel toric. After image registration and layer segmentation, analyses were performed of the first hyper-reflective layer (HRL), the epithelial basement membrane (EBL) and the epithelial thickness (HRL to EBL). A root mean square difference (RMSD) of the layer profiles and the thickness change between the morning and afternoon measurements, was used to assess the effect of the contact lens on the corneoscleral morphology. Results. The soft contact lenses had a statistically significant effect on the morphology of the anterior segment layers (p <0.001). The average amounts of change for the three lenses (average RMSD values) for the corneal region were lower (3.93±1.95 µm for the HRL and 4.02±2.14 µm for the EBL) than those measured in the limbal/scleral region (11.24±6.21 µm for the HRL and 12.61±6.42 µm for the EBL). Similarly, averaged across the three lenses, the RMSD in epithelial thickness was lower in the cornea (2.84±0.84 µm) than the limbal/scleral (5.47±1.71 µm) region. Post-hoc analysis showed that ocular surface changes were significantly smaller with the silicone hydrogel sphere lens than both the silicone hydrogel toric (p<0.005) and hydrogel sphere (p<0.02) for the combined HRL and EBL data. Conclusions. In this preliminary study, we have shown that soft contact lenses can produce small but significant changes in the morphology of the limbal/scleral region and that OCT technology is useful in assessing these changes. The clinical significance of these changes is yet to be determined.

Effect of CT electron density identification on Monte Carlo simulations of radiotherapeutic treatments

Introduction: The accurate identification of tissue electron densities is of great importance for Monte Carlo (MC) dose calculations. When converting patient CT data into a voxelised format suitable for MC simulations, however, it is common to simplify the assignment of electron densities so that the complex tissues existing in the human body are categorized into a few basic types. This study examines the effects that the assignment of tissue types and the calculation of densities can have on the results of MC simulations, for the particular case of a Siemen’s Sensation 4 CT scanner located in a radiotherapy centre where QA measurements are routinely made using 11 tissue types (plus air). Methods: DOSXYZnrc phantoms are generated from CT data, using the CTCREATE user code, with the relationship between Hounsfield units (HU) and density determined via linear interpolation between a series of specified points on the ‘CT-density ramp’ (see Figure 1(a)). Tissue types are assigned according to HU ranges. Each voxel in the DOSXYZnrc phantom therefore has an electron density (electrons/cm3) defined by the product of the mass density (from the HU conversion) and the intrinsic electron density (electrons /gram) (from the material assignment), in that voxel. In this study, we consider the problems of density conversion and material identification separately: the CT-density ramp is simplified by decreasing the number of points which define it from 12 down to 8, 3 and 2; and the material-type-assignment is varied by defining the materials which comprise our test phantom (a Supertech head) as two tissues and bone, two plastics and bone, water only and (as an extreme case) lead only. The effect of these parameters on radiological thickness maps derived from simulated portal images is investigated. Results & Discussion: Increasing the degree of simplification of the CT-density ramp results in an increasing effect on the resulting radiological thickness calculated for the Supertech head phantom. For instance, defining the CT-density ramp using 8 points, instead of 12, results in a maximum radiological thickness change of 0.2 cm, whereas defining the CT-density ramp using only 2 points results in a maximum radiological thickness change of 11.2 cm. Changing the definition of the materials comprising the phantom between water and plastic and tissue results in millimetre-scale changes to the resulting radiological thickness. When the entire phantom is defined as lead, this alteration changes the calculated radiological thickness by a maximum of 9.7 cm. Evidently, the simplification of the CT-density ramp has a greater effect on the resulting radiological thickness map than does the alteration of the assignment of tissue types. Conclusions: It is possible to alter the definitions of the tissue types comprising the phantom (or patient) without substantially altering the results of simulated portal images. However, these images are very sensitive to the accurate identification of the HU-density relationship. When converting data from a patient’s CT into a MC simulation phantom, therefore, all possible care should be taken to accurately reproduce the conversion between HU and mass density, for the specific CT scanner used. Acknowledgements: This work is funded by the NHMRC, through a project grant, and supported by the Queensland University of Technology (QUT) and the Royal Brisbane and Women's Hospital (RBWH), Brisbane, Australia. The authors are grateful to the staff of the RBWH, especially Darren Cassidy, for assistance in obtaining the phantom CT data used in this study. The authors also wish to thank Cathy Hargrave, of QUT, for assistance in formatting the CT data, using the Pinnacle TPS. Computational resources and services used in this work were provided by the HPC and Research Support Group, QUT, Brisbane, Australia.

Diurnal variation of corneal shape and thickness

Purpose: To investigate associations between the diurnal variation in a range of corneal parameters, including anterior and posterior corneal topography, and regional corneal thickness. ----- Methods: Fifteen subjects had their corneas measured using a rotating Scheimpflug camera (Pentacam) every 3-7 hours over a 24-hour period. Anterior and posterior corneal axial curvature, pachymetry and anterior chamber depth were analysed. The best fitting corneal sphero-cylinder from the axial curvature, and the average corneal thickness for a series of different corneal regions were calculated. Intraocular pressure and axial length were also measured at each measurement session. Repeated measures ANOVA were used to investigate diurnal change in these parameters. Analysis of covariance was used to examine associations between the measured ocular parameters. ----- Results: Significant diurnal variation was found to occur in both the anterior and posterior corneal curvature and in the regional corneal thickness. Flattening of the anterior corneal best sphere was observed at the early morning measurement (p < 0.0001). The posterior cornea also underwent a significant steepening (p < 0.0001) and change in astigmatism 90/180° at this time. A significant swelling of the cornea (p < 0.0001) was also found to occur immediately after waking. Highly significant associations were found between the diurnal variation in corneal thickness and the changes in corneal curvature. ----- Conclusions: Significant diurnal variation occurs in the regional thickness and the shape of the anterior and posterior cornea. The largest changes in the cornea were typically evident upon waking. The observed non-uniform regional corneal thickness changes resulted in a steepening of the posterior cornea, and a flattening of the anterior cornea to occur at this time.

Mind change complexity of learning logic programs

The present paper motivates the study of mind change complexity for learning minimal models of length-bounded logic programs. It establishes ordinal mind change complexity bounds for learnability of these classes both from positive facts and from positive and negative facts. Building on Angluin’s notion of finite thickness and Wright’s work on finite elasticity, Shinohara defined the property of bounded finite thickness to give a sufficient condition for learnability of indexed families of computable languages from positive data. This paper shows that an effective version of Shinohara’s notion of bounded finite thickness gives sufficient conditions for learnability with ordinal mind change bound, both in the context of learnability from positive data and for learnability from complete (both positive and negative) data. Let Omega be a notation for the first limit ordinal. Then, it is shown that if a language defining framework yields a uniformly decidable family of languages and has effective bounded finite thickness, then for each natural number m >0, the class of languages defined by formal systems of length <= m: • is identifiable in the limit from positive data with a mind change bound of Omega (power)m; • is identifiable in the limit from both positive and negative data with an ordinal mind change bound of Omega × m. The above sufficient conditions are employed to give an ordinal mind change bound for learnability of minimal models of various classes of length-bounded Prolog programs, including Shapiro’s linear programs, Arimura and Shinohara’s depth-bounded linearly covering programs, and Krishna Rao’s depth-bounded linearly moded programs. It is also noted that the bound for learning from positive data is tight for the example classes considered.

Diurnal Variation of Retinal Thickness with Spectral Domain OCT

Purpose. To investigate whether diurnal variation occurs in retinal thickness measures derived from spectral domain optical coherence tomography (SD-OCT). Methods. Twelve healthy adult subjects had retinal thickness measured with SD-OCT every 2 h over a 10 h period. At each measurement session, three average B-scan images were derived from a series of multiple B-scans (each from a 5 mm horizontal raster scan along the fovea, containing 1500 A-scans/B-scan) and analyzed to determine the thickness of the total retina, as well as the thickness of the outer retinal layers. Average thickness values were calculated at the foveal center, at the 0.5 mm diameter foveal region, and for the temporal parafovea (1.5 mm from foveal center) and nasal parafovea (1.5 mm from foveal center). Results. Total retinal thickness did not exhibit significant diurnal variation in any of the considered retinal regions (p > 0.05). Evidence of significant diurnal variation was found in the thickness of the outer retinal layers (p < 0.05), with the most prominent changes observed in the photoreceptor layers at the foveal center. The photoreceptor inner and outer segment layer thickness exhibited mean amplitude (peak to trough) of daily change of 7 ± 3 μm at the foveal center. The peak in thickness was typically observed at the third measurement session (mean measurement time, 13:06). Conclusions. The total retinal thickness measured with SD-OCT does not exhibit evidence of significant variation over the course of the day. However, small but significant diurnal variation occurs in the thickness of the foveal outer retinal layers.

Axial length and choroidal thickness changes accompanying prolonged accommodation in myopes and emmetropes

The time course of elongation and recovery of axial length associated with a 30 minute accommodative task was studied using optical low coherence reflectometry in a population of young adult myopic (n = 37) and emmetropic (n = 22) subjects. Ten of the 59 subjects were excluded from analysis either due to inconsistent accommodative response, or incomplete anterior biometry data. Those subjects with valid data (n = 49) were found to exhibit a significant axial elongation immediately following the commencement of a 30 minute, 4 D accommodation task, which was sustained for the duration of the task, and ¬was evident to a lesser extent immediately following task cessation. During the accommodation task, on average, the myopic subjects exhibited 22 ± 34 µm, and the emmetropic subjects 6 ± 22 µm of axial elongation, however the differences in axial elongation between the myopic and emmetropic subjects were not statistically significant (p = 0.136). Immediately following the completion of the task, the myopic subjects still exhibited an axial elongation (mean magnitude 12 ± 28 µm), that was significantly greater (p < 0.05) than the changes in axial length observed in the emmetropic subjects (mean change -3 ± 16 µm). Axial length had returned to baseline levels 10 minutes after completion of the accommodation task. The time for recovery from accommodation-induced axial elongation was greater in myopes, which may reflect differences in the biomechanical properties of the globe associated with refractive error. Changes in subfoveal choroidal thickness were able to be measured in 37 of the 59 subjects, and a small amount of choroidal thinning was observed during the accommodation task that was statistically significant in the myopic subjects (p < 0.05). These subfoveal choroidal changes could account for some but not all of the increased axial length during accommodation.

Monocular myopic defocus and daily changes in axial length and choroidal thickness of human eyes

Recent research indicates that brief periods (60 minutes) of monocular defocus lead to small but significant changes in human axial length. However, the effects of longer periods of defocus on the axial length of human eyes are unknown. We examined the influence of a 12 hour period of monocular myopic defocus on the natural daily variations occurring in axial length and choroidal thickness of young adult emmetropes. 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 for 13 emmetropic young adults over three consecutive days. The natural daily rhythms (Day 1, baseline day, no defocus), the daily rhythms with monocular myopic defocus (Day 2, defocus day, +1.50 DS spectacle lens over the right eye), and the recovery from any defocus induced changes (Day 3, recovery day, no defocus) were all examined. Significant variations over the course of the day were observed in both axial length and choroidal thickness on each of the three measurement days (p<0.0001). The magnitude and timing of the daily variations in axial length and choroidal thickness were significantly altered with the monocular myopic defocus on day 2 (p<0.0001). Following the introduction of monocular myopic defocus, the daily peak in axial length occurred approximately 6 hours later, and the peak in choroidal thickness approximately 8.5 hours earlier in the day compared to days 1 and 3 (with no defocus). The mean amplitude (peak to trough) of change in axial length (0.030 ± 0.012 on day 1, 0.020 ± 0.010 on day 2 and 0.033 ± 0.012 mm on day 3) and choroidal thickness (0.030 ± 0.007 on day 1, 0.022 ± 0.006 on day 2 and 0.027 ± 0.009 mm on day 3) were also significantly different between the three days (both p<0.05). The introduction of monocular myopic defocus disrupts the daily variations in axial length and choroidal thickness of human eyes (in terms of both amplitude and timing) that return to normal the following day after removal of the defocus.

Comparison of three different dressings for partial thickness burns in children : study protocol for a randomised controlled trial

BACKGROUND: In the paediatric population, pain and distress associated with burn injuries during wound care procedures remain a constant challenge. Although silver dressings are the gold standard for burn care in Australasia, very few high-level trials have been conducted that compare silver dressings to determine which will provide the best level of care clinically. Therefore, for paediatric patients in particular, identifying silver dressings that are associated with lower levels of pain and rapid wound re-epithelialisation is imperative. This study will determine whether there is a difference in time to re-epithelialisation and pain and distress experienced during wound care procedures among Acticoat, Acticoat combined with Mepitel and Mepilex Ag dressings for acute, paediatric partial thickness burns. METHODS/DESIGN: Children aged 0 to 15 years with an acute partial thickness (superficial partial to deep partial thickness inclusive) burn injury and a burn total body surface area of change until complete wound re-epithelialisation occurs or skin grafting is required. Additional data collected will include infection status at each dressing change, physical function, scar outcome and scar management requirements, cost effectiveness of each dressing and staff perspectives of the dressings. DISCUSSION: The results of this study will determine the effects of three commonly used silver and silicone burn dressing combinations on the rate of wound re-epithelialisation and pain experienced during dressing procedures in acute, paediatric partial thickness burn injuries. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12613000105741.

The effect of topical adrenergic and anticholinergic agents on the choroidal thickness of young healthy adults

The human choroid is capable of rapidly changing its thickness in response to a variety of stimuli. However little is known about the role of the autonomic nervous system in the regulation of the thickness of the choroid. Therefore, we investigated the effect of topical parasympatholytic and sympathomimetic agents upon the choroidal thickness and ocular biometrics of young healthy adult subjects. Fourteen subjects (mean age 27.9 ± 4 years) participated in this randomized, single-masked, placebo-controlled study. Each subject had measurements of choroidal thickness (ChT) and ocular biometrics of their right eye taken before, and then 30 and 60 min following the administration of topical pharmacological agents. Three different drugs: 2% homatropine hydrobromide, 2.5% phenylephrine hydrochloride and a placebo (0.3% hydroxypropyl methylcellulose) were tested in all subjects; each on different days (at the same time of the day) in randomized order. Participants were masked to the pharmacological agent being used at each testing session. The instillation of 2% homatropine resulted in a small but significant increase in subfoveal ChT at 30 and 60 min after drug instillation (mean change 7 ± 3 μm and 14 ± 2 μm respectively; both p < 0.0001). The parafoveal choroid also exhibited a similar magnitude, significant increase in thickness with time after 2% homatropine (p < 0.001), with a mean change of 7 ± 0.3 μm and 13 ± 1 μm (in the region located 0.5 mm from the fovea center), 6 ± 1 μm and 12.5 ± 1 μm (1 mm from the fovea center) and 6 ± 2 μm and 12 ± 2 μm (1.5 mm from the fovea center) after 30 and 60 min respectively. Axial length decreased significantly 60 min after homatropine (p < 0.01). There were also significant changes in lens thickness (LT) and anterior chamber depth (ACD) (p < 0.05) associated with homatropine instillation. No significant changes in choroidal thickness, or ocular biometrics were found after 2.5% phenylephrine or placebo at any examination points (p > 0.05). In human subjects, significant increases in subfoveal and parafoveal choroidal thickness occurred after administration of 2% homatropine and this implies an involvement of the parasympathetic system in the control of choroidal thickness in humans.

Mapping cortical change in Alzheimer's disease, brain development, and schizophrenia

This paper describes algorithms that can identify patterns of brain structure and function associated with Alzheimer's disease, schizophrenia, normal aging, and abnormal brain development based on imaging data collected in large human populations. Extraordinary information can be discovered with these techniques: dynamic brain maps reveal how the brain grows in childhood, how it changes in disease, and how it responds to medication. Genetic brain maps can reveal genetic influences on brain structure, shedding light on the nature-nurture debate, and the mechanisms underlying inherited neurobehavioral disorders. Recently, we created time-lapse movies of brain structure for a variety of diseases. These identify complex, shifting patterns of brain structural deficits, revealing where, and at what rate, the path of brain deterioration in illness deviates from normal. Statistical criteria can then identify situations in which these changes are abnormally accelerated, or when medication or other interventions slow them. In this paper, we focus on describing our approaches to map structural changes in the cortex. These methods have already been used to reveal the profile of brain anomalies in studies of dementia, epilepsy, depression, childhood- and adult-onset schizophrenia, bipolar disorder, attention-deficit/hyperactivity disorder, fetal alcohol syndrome, Tourette syndrome, Williams syndrome, and in methamphetamine abusers. Specifically, we describe an image analysis pipeline known as cortical pattern matching that helps compare and pool cortical data over time and across subjects. Statistics are then defined to identify brain structural differences between groups, including localized alterations in cortical thickness, gray matter density (GMD), and asymmetries in cortical organization. Subtle features, not seen in individual brain scans, often emerge when population-based brain data are averaged in this way. Illustrative examples are presented to show the profound effects of development and various diseases on the human cortex. Dynamically spreading waves of gray matter loss are tracked in dementia and schizophrenia, and these sequences are related to normally occurring changes in healthy subjects of various ages.

Regional changes in choroidal thickness associated with accommodation

Purpose. To characterize the changes occurring in choroidal thickness (ChT) across the posterior pole during accommodation using enhanced-depth imaging optical coherence tomography (OCT). Methods. Forty participants (mean age 21 ± 2 years) had measures of ChT and ocular biometry taken during accommodation to 0, 3, and 6 diopter (D) stimuli, with the Spectralis OCT and Lenstar biometer. A Badal optometer and cold mirror system was mounted on both instruments, allowing measurement collection while subjects viewed an external fixation target at varying accommodative demands. Results. The choroid exhibited significant thinning during accommodation to the 6 D stimulus in both subfoveal (mean change, −5 ± 7 μm) and parafoveal regions (P < 0.001). The magnitude of these changes varied by parafoveal meridian, with the largest changes seen in the temporal (−9 ± 12 μm) and inferotemporal (−8 ± 8 μm) meridians (P < 0.001). Axial length increased with accommodation (mean change, +5 ± 11 μm at 3 D, +14 ± 13 μm at 6 D), and these changes were weakly negatively associated with the choroidal changes (r2 = 0.114, P < 0.05). Conclusions. A small, but significant thinning of the choroid was observed at the 6 D accommodation demand, which was greatest in the temporal and inferotemporal parafoveal choroid, and increased with increasing eccentricity from the fovea. The regional variation in the parafoveal thinning corresponds to the distribution of the nonvascular smooth muscle within the uvea, which may implicate these cells as the potential mechanism by which the choroid thins during accommodation.

Longitudinal changes in choroidal thickness and eye growth in childhood

PURPOSE To examine longitudinal changes in choroidal thickness and axial length in a population of children with a range of refractive errors. METHODS One hundred and one children (41 myopes and 60 nonmyopes) aged 10 to 15 years participated in this prospective, observational longitudinal study. For each child, 6-month measures of choroidal thickness (using enhanced depth imaging optical coherence tomography) and axial ocular biometry were collected four times over an 18-month period. Linear mixed-models were used to examine the longitudinal changes in choroidal thickness and the relationship between changes in choroidal thickness and axial eye growth over the study period. RESULTS A significant group mean increase in subfoveal choroidal thickness was observed over 18 months (mean increase 13 6 22 lm, P < 0.001). Myopic children exhibited significantly thinner choroids compared with nonmyopic children (P < 0.001), although there was no significant time by refractive group interaction (P ¼ 0.46), indicating similar changes in choroidal thickness over time in myopes and nonmyopes. However, a significant association between the change in choroidal thickness and the change in axial length over time was found (P < 0.001, β = −0.14). Children showing faster axial eye growth exhibited significantly less choroidal thickening over time compared with children showing slower axial eye growth. CONCLUSIONS A significant increase in choroidal thickness occurs over an 18-month period in normal 10- to 15-year-old children. Children undergoing faster axial eye growth exhibited less thickening and, in some cases, a thinning of the choroid. These findings support a potential role for the choroid in the mechanisms regulating eye growth in childhood.