The statistics of refractive error maps : managing wavefront aberration analysis without Zernike polynomials

The refractive error of a human eye varies across the pupil and therefore may be treated as a random variable. The probability distribution of this random variable provides a means for assessing the main refractive properties of the eye without the necessity of traditional functional representation of wavefront aberrations. To demonstrate this approach, the statistical properties of refractive error maps are investigated. Closed-form expressions are derived for the probability density function (PDF) and its statistical moments for the general case of rotationally-symmetric aberrations. A closed-form expression for a PDF for a general non-rotationally symmetric wavefront aberration is difficult to derive. However, for specific cases, such as astigmatism, a closed-form expression of the PDF can be obtained. Further, interpretation of the distribution of the refractive error map as well as its moments is provided for a range of wavefront aberrations measured in real eyes. These are evaluated using a kernel density and sample moments estimators. It is concluded that the refractive error domain allows non-functional analysis of wavefront aberrations based on simple statistics in the form of its sample moments. Clinicians may find this approach to wavefront analysis easier to interpret due to the clinical familiarity and intuitive appeal of refractive error maps.

Variation of the Stiles-Crawford effect with accommodation and myopia

Background: Mechanical forces either due to accommodation or myopia may stretch the retina and/or cause shear between the retina and choroid. This can be investigated by making use of the Stiles-Crawford effect (SCE), which is the phenomenon of light changing in apparent brightness as it enters through different positions in the pupil. The SCE can be measured by psychophysical and objective techniques, with the SCE parameters being directionality (rate of change across the pupil), and orientation (the location of peak sensitivity in the pupil). Aims: 1. To study the changes in foveal SCE with accommodation in emmetropes and myopes using a subjective (psychophysical) technique. 2. To develop and evaluate a quick objective technique of measuring the SCE using the multifocal electroretinogram. Methods: The SCE was measured in 6 young emmetropes and 6 young myopes for up to 8 D accommodation stimulus with a psychophysical technique and its variants. An objective technique using the multifocal electroretinogram was developed and evaluated with 5 emmetropes. Results: Using the psychophysical technique, the SCE directionality increased by similar amounts in both emmetropes and myopes as accommodation increased, with an increase of 15-20% with 6 D of accommodation. However, there were no significant orientation changes. Additional measurements showed that most of the change in the directionality was probably an artefact of optical factors such as higher-order aberrations and accommodative lag rather a true effect of accommodation. The multifocal technique demonstrated the presence of the SCE, but results were noisy and too variable to detect any changes in SCE directionality or orientation with accommodation. Conclusion: There is little true change in the SCE with accommodation responses up to 6 D in either emmetropes or myopes, although it is possible that substantial changes might occur at very high accommodation levels. The objective technique using the multifocal electroretinogram was quicker and less demanding for the subjects than the psychophysical technique, but as implemented in this thesis, it is not a reliable method of measuring the SCE.

Jack's Bay

Jack's Bay expands understandings of the role of photographic media in the representation of landscapes. It does so by combining architectural construction with B&W photographic processing techniques. A purpose-built room-sized camera obscura is first constructed over a portion of the landscape to be recorded. Photosensitive paper is applied to the interior wall surfaces and is exposed to the inverted light entering a small aperture. These photographs are subsequently developed within the camera itself and consequently 'suffer' embellishments and aberrations from the makeshift darkroom conditions. In this way the specificity of both the landscape and the event of its recording are registered in the final image. Many images were destroyed in the process. The idea of the work is to help the viewer reflect on the role media plays in our understanding of landscape and to thus question the means by which they themselves record and interpret landscape representations.

Corackerup Breakaway

Corackerup Breakaway expands understandings of the role of photographic media in the representation of landscapes. It does so by combining architectural construction with B&W photographic processing techniques. A purpose-built room-sized camera obscura is first constructed over a portion of the landscape to be recorded. Photosensitive paper is applied to the interior wall surfaces and is exposed to the inverted light entering a small aperture. These photographs are subsequently developed within the camera itself and consequently 'suffer' embellishments and aberrations from the makeshift darkroom conditions. In this way the specificity of both the landscape and the event of its recording are registered in the final image. Many images were destroyed in the process. The idea of the work is to help the viewer reflect on the role media plays in our understanding of landscape and to thus question the means by which they themselves record and interpret landscape representations.

Working sheep

Working Sheep expands understandings of the role of photographic media in the representation of landscapes. It does so by combining architectural construction with B&W photographic processing techniques. A purpose-built room-sized camera obscura is first constructed over a portion of the landscape to be recorded. Photosensitive paper is applied to the interior wall surfaces and is exposed to the inverted light entering a small aperture. These photographs are subsequently developed within the camera itself and consequently 'suffer' embellishments and aberrations from the makeshift darkroom conditions. In this way the specificity of both the landscape and the event of its recording are registered in the final image. Many images were destroyed in the process. The idea of the work is to help the viewer reflect on the role media plays in our understanding of landscape and to thus question the means by which they themselves record and interpret landscape representations.

Subjective blur limits for cylinder

Purpose: To compare subjective blur limits for cylinder and defocus. ---------- Method: Blur was induced with a deformable, adaptive-optics mirror when either the subjects’ own astigmatisms were corrected or when both astigmatisms and higher-order aberrations were corrected. Subjects were cyclopleged and had 5 mm artificial pupils. Black letter targets (0.1, 0.35 and 0.6 logMAR) were presented on white backgrounds. Results: For ten subjects, blur limits were approximately 50% greater for cylinder than for defocus (in diopters). While there were considerable effects of axis for individuals, overall this was not strong, with the 0° (or 180°) axis having about 20% greater limits than oblique axes. In a second experiment with text (equivalent in angle to N10 print at 40 cm distance), cylinder blur limits for 6 subjects were approximately 30% greater than those for defocus; this percentage was slightly smaller than for the three letters. Blur limits of the text were intermediate between those of 0.35 logMAR and 0.6 logMAR letters. Extensive blur limit measurements for one subject with single letters did not show expected interactions between target detail orientation and cylinder axis. ---------- Conclusion: Subjective blur limits for cylinder are 30%-50% greater than those for defocus, with the overall influence of cylinder axis being 20%.

Estimation of the depth focus from wavefront measurements

It is possible to estimate the depth of focus (DOF) of the eye directly from wavefront measurements using various retinal image quality metrics (IQMs). In such methods, DOF is defined as the range of defocus error that degrades the retinal image quality calculated from IQMs to a certain level of the maximum value. Although different retinal image quality metrics are used, currently there have been two arbitrary threshold levels adopted, 50% and 80%. There has been limited study of the relationship between these threshold levels and the actual measured DOF. We measured the subjective DOF in a group of 17 normal subjects, and used through-focus augmented visual Strehl ratio based on optical transfer function (VSOTF) derived from their wavefront aberrations as the IQM. For each subject, a VSOTF threshold level was derived that would match the subjectively measured DOF. Significant correlation was found between the subject’s estimated threshold level and the HOA RMS (Pearson’s r=0.88, p<0.001). The linear correlation can be used to estimate the threshold level for each individual subject, subsequently leading to a method for estimating individual’s DOF from a single measurement of their wavefront aberrations.

Depth of focus and visual acuity with primary and secondary spherical aberration

It is known that the depth of focus (DOF) of the human eye can be affected by the higher order aberrations. We estimated the optimal combinations of primary and secondary Zernike spherical aberration to expand the DOF and evaluated their efficiency in real eyes using an adaptive optics system. The ratio between increased DOF and loss of visual acuity was used as the performance indicator. The results indicate that primary or secondary spherical aberration alone shows similar effectiveness in extending the DOF. However, combinations of primary and secondary spherical aberration with different signs provide better efficiency for expanding the DOF. This finding suggests that the optimal combinations of primary and secondary spherical aberration may be useful in the design of optical presbyopic corrections. © 2011 Elsevier Ltd. All rights reserved.

Heidegger's hippies : a dissenting voice on "the problem of the subject"

This is a deliberately contentious paper about the future of the socio-political sphere in the West based on what we know about its past. I argue that the predominant public discourse in Western countries is best characterised as one of selective forgetfulness; a semi-blissful, amnesiacal state of collective dementia that manifests itself in symbolic idealism: informationalism. Informationalism is merely the latest form of idealism. It is a lot like religion insofar as it causally relates abstract concepts with reality and, consequently, becomes confused between the two. Historically, this has proven to be a dangerous state of affairs, especially when elites becomes confused between ideas about how a society should work, and the way it actually does work. Central to the idealism of the information age, at least in intellectual spheres, is the so called "problem of the subject". I argue that the "problem of the subject" is a largely synthetic, destabilising, and ultimately fruitless theoretical abstraction which turns on a synthetically derived, generalised intradiscursive space; existentialist nihilism; and the theoretical baubles of ontological metaphysics. These philosophical aberrations are, in turn, historically concomitant with especially destructive political and social configurations. This paper sketches a theoretical framework for identity formation which rejects the problem of the subject, and proposes potential resources, sources, and strategies with which to engage the idealism that underpins this obfuscating problematic in an age of turbulent social uncertainty. Quite simply, I turn to history as the source of human identity. While informationalism, like religion, is mostly focused on utopian futures, I assert that history, not the future, holds the solutions for substantive problematics concerning individual and social identities. I argue here that history, language, thought, and identity are indissolubly entangled and so should be understood as such: they are the fundamental parts of 'identities in action'. From this perspective, the ‘problem of the subject’ becomes less a substantive intellectual problematic and more a theoretical red herring.

Osteopontin is a downstream effector of the PI3-kinase pathway in melanomas that is inversely correlated with functional PTEN

The tumor suppressor PTEN antagonizes phosphatidylinositol 3-kinase (PI3K), which contributes to tumorigenesis in many cancer types. While PTEN mutations occur in some melanomas, their precise mechanistic consequences have yet to be elucidated. We sought to identify novel downstream effectors of PI3K using a combination of genomic and functional tests. Microarray analysis of 53 melanoma cell lines identified 610 genes differentially expressed (P<0.05) between wild-type lines and those with PTEN aberrations. Many of these genes are known to be involved in the PI3K pathway and other signaling pathways influenced by PTEN. Validation of differential gene expression by qRT-PCR was performed in the original 53 cell lines and an independent set of 18 melanoma lines with known PTEN status. Osteopontin (OPN), a secreted glycophosphoprotein that contributes to tumor progression, was more abundant at both the mRNA and protein level in PTEN mutants. The inverse correlation between OPN and PTEN expression was validated (P<0.02) by immunohistochemistry using melanoma tissue microarrays. Finally, treatment of cell lines with the PI3K inhibitor LY294002 caused a reduction in expression of OPN. These data indicate that OPN acts downstream of PI3K in melanoma and provides insight into how PTEN loss contributes to melanoma development.

CDKN2A is not the principal target of deletions on the short arm of chromosome 9 in neuroendocrine (Merkel cell) carcinoma of the skin

The majority of small-cell lung cancers (SCLCs) express p16 but not pRb. Given our previous study showing loss of pRb in Merkel cell carcinoma (MCC)/neuroendocrine carcinoma of the skin and the clinicopathological similarities between SCLC and MCC, we wished to determine if this was also the case in MCC. Twenty-nine MCC specimens from 23 patients were examined for deletions at 10 loci on 9p and 1 on 9q. No loss of heterozygosity (LOH) was seen in 9 patients including 2 for which tumour and cell line DNAs were examined. Four patients had LOH for all informative loci on 9p. Ten tumours showed more limited regions of loss on 9p, and from these 2 common regions of deletion were determined. Half of all informative cases had LOH at D9S168, the most telomeric marker examined, and 3 specimens showed loss of only D9S168. A second region (IFNA-D9S126) showed LOH in 10 (44%) cases, and case MCC26 showed LOH for only D9S126, implicating genes centromeric of the CDKN2A locus. No mutations in the coding regions of p16 were seen in 7 cell lines tested, and reactivity to anti-p16 antibody was seen in all 11 tumour specimens examined and in 6 of 7 cell lines from 6 patients. Furthermore, all cell lines examined reacted with anti-p14(ARF) antibody. These results suggest that neither transcript of the CDKN2A locus is the target of deletions on 9p in MCC and imply the existence of tumour-suppressor genes mapping both centromeric and telomeric of this locus.

Mutations in exon 3 of the beta-catenin gene are rare in melanoma cell lines

Mutations in exon 3 of the CTNNB1 gene encoding beta-catenin have been reported in colorectal cancer cell lines and tumours. Although one study reported mutations or deletions affecting beta-catenin in 20% of melanoma cell lines, subsequent reports detected a much lower frequency of aberrations in uncultured melanomas. To determine whether this difference in mutation frequency reflected an in vitro culturing artefact, exon 3 of CTNNB1 was screened in a panel of 62 melanoma cell lines. In addition, reverse transcription-polymerase chain reaction (RT-PCR) was performed to detect intragenic deletions affecting exon 3. One out of 62 (1.6%) cell lines was found to carry a mutation, indicating that aberration of the Wnt-1/wingless pathway through activation of beta-catenin is a rare event, even in melanoma cell lines.

PTEN inactivation is rare in melanoma tumours but occurs frequently in melanoma cell lines

Deletions detected in cytogenetic and loss of heterozygosity (LOH) studies indicate that at least one tumour suppressor gene maps to the long arm of chromosome 10. Previous deletion mapping studies have observed LOH on 10q in about 30% of melanomas analysed. The PTEN gene, mapping to chromosome band 10q23.3, encodes a protein with both lipid and protein phosphatase activity. Somatic mutations and deletions in have been detected in a variety of cell lines and tumours, including melanoma samples. We performed mutation analyses and extensive allelic loss studies to investigate the role this gene plays in melanoma pathogenesis. We found that a total of 34 out of 57 (60%) melanoma cell lines carried hemizygous deletions of chromosome 10q encompassing the PTEN locus. A further three cell lines carried smaller deletions excluding PTEN. Inactivation of both PTEN alleles by exon-specific homozygous deletion or mutation was observed in 13 out of 57 (23%) melanoma cell lines. The mutation spectrum observed does not indicate an important role for ultraviolet radiation in the genesis of these mutations, and evidence from three cell lines supports the acquisition of PTEN aberrations in culture. Ten out of 49 (20%) matched melanoma tumour/normal samples harboured hemizygous deletions of either the whole chromosome or most of the long arm. Mutations within were detected in only one of the 10 tumours demonstrating LOH at 10q23 that were analysed. These results suggest that PTEN inactivation may be important for the propagation of melanoma cells in culture, and that another chromosome 10 tumour suppressor gene may be important for melanoma pathogenesis.

Ocular characteristics in myopic anisometropia

PURPOSE: To investigate the interocular symmetry of ocular optical, biometric and biomechanical characteristics between the more and less ametropic eyes of myopic anisometropes. METHODS: Thirty-four young, healthy myopic anisometropic adults (≥ 1 D spherical equivalent difference between eyes) without amblyopia or strabismus were recruited. A range of biometric and optical parameters were measured in the more and less ametropic eye of each subject including; axial length, ocular aberrations, intraocular pressure and corneal topography, thickness and biomechanics. Morphology of the anterior eye in primary and downward gaze was examined using custom software analysis of high resolution digital images. Ocular sighting dominance was assessed using the hole-in-the-card test. RESULTS: Mean absolute spherical equivalent anisometropia was 1.74 ± 0.74 D. There was a strong correlation between the degree of anisometropia and the interocular difference in axial length (r = 0.81, p < 0.001). The more and less ametropic fellow eyes displayed a high degree of interocular symmetry for the majority of biometric, biomechanical and optical parameters measured. When the level of anisometropia exceeded 1.75 D (n = 10), the more myopic eye was the dominant sighting eye in nine of these ten subjects. Subjects with greater levels of anisometropia (> 1.75 D) also showed high levels of correlation between the dominant and non-dominant eyes in their biometric, biomechanical and optical characteristics. CONCLUSIONS: Although significantly different in axial length, anisometropic eyes display a high degree of interocular symmetry for a range of anterior eye biometrics and optical parameters. For higher levels of anisometropia, the more myopic eye tends to be the dominant sighting eye.