Ocular biometric correlates of early-and late-onset myopia

Myopia is a refractive condition and develops because either the optical power of the eye is abnormally great or the eye is abnormally long, the optical consequences being that the focal length of the eye is too short for the physical length of the eye. The increase in axial length has been shown to match closely the dioptric error of the eye, in that a lmm increase in axial length usually generates 2 to 3D of myopia. The most common form of myopia is early-onset myopia (EO M) which occurs between 6 to 14 years of age. The second most common form of myopia is late-onset myopia (LOM) which emerges in late teens or early twenties, at a time when the eye should have ceased growing. The prevalence of LOM is increasing and research has indicated a link with excessive and sustained nearwork. The aim of this thesis was to examine the ocular biometric correlates associated with LOM and EOM development and progression. Biometric data was recorded on SO subjects, aged 16 to 26 years. The group was divided into 26 emmetropic subjects and 24 myopic subjects. Keratometry, corneal topography, ultrasonography, lens shape, central and peripheral refractive error, ocular blood flow and assessment of accommodation were measured on three occasions during an ISmonth to 2-year longitudinal study. Retinal contours were derived using a specially derived computer program. The thesis shows that myopia progression is related to an increase in vitreous chamber depth, a finding which supports previous work. The myopes exhibited hyperopic relative peripheral refractive error (PRE) and the emmetropes exhibited myopic relative PRE. Myopes demonstrated a prolate retinal shape and the retina became more prolate with myopia progression. The results show that a longitudinal, rather than equatorial, increase in the posterior segment is the principal structural correlate of myopia. Retinal shape, relative PRE and the ratio of axial length to corneal curvature have been indicated, in this thesis, as predictive factors for myopia onset and development. Data from this thesis demonstrates that myopia progression in the LOM group is the result of an increase in anterior segment power, owing to an increase in lens thickness, in conjunction with posterior segment elongation. Myopia progression in the EOM group is the product of a long posterior segment, which over-compensates for a weak anterior segment power. The weak anterior segment power in the EOM group is related to a combination of crystalline lens thinning and surface flattening. The results presented in this thesis confirm that posterior segment elongation is the main structural correlate in both EOM and LOM progression. The techniques and computer programs employed in the thesis are reproducible and robust providing a valuable framework for further myopia research and assessment of predictive factors.

Physiological and pathological human ocular perfusion characteristics

There were three principle aims to this thesis. Firstly, the acquisition protocols of clinical blood flow apparatus were investigated in order to optimise them for both cross-sectional and longitudinal application. Secondly, the effects of physiological factors including age and systematic circulation on ocular blood flow were investigated. Finally, the ocular perfusion characteristics of patients diagnosed with ocular diseases considered to be of a vascular origin were investigated. The principle findings of this work are:- 1) Optimisation of clinical investigationsPhotodiode sensitivity of the scanning laser Doppler flowmeter should be kept within a range of 70-150 DC when acquiring images of the retina and optic nerve head in order to optimise the reproducibility of capillary blood flow measures. Account of the physiological spatial variation in retinal blood flow measures can be made using standard analysis protocols of the scanning laser Doppler flowmeter combined with a local search strategy. Measurements of pulsatile ocular blood flow using the ocular blood flow analyser are reproducible, however this reproducibility can be improved when consecutive intraocular pressure pulses are used to calculate pulsatile ocular blood flow. Spectral analysis of the intraocular pressure pulse-wave is viable and identifies the first four harmonic components of the waveform. 2) Physiological variation in ocular perfusionAge results in a significant reduction in perfusion of the retinal microcirculation, which is not evident in larger vessel beds such as the choroid. Despite known asymmetry in the systemic vasculature, no evidence of interocular asymmetry in ocular perfusion is apparent. 3) Pathological variation in ocular perfusionIn primary open angle glaucoma, perfusion is reduced in the retinal microcirculation of patients classified as having early to moderate visual field defects. However, ocular pulsatility defects are masked when patients and subjects are matched for systemic variables (pulse rate and mean arterial pressure); differentiation is facilitated by the application of waveform analysis to the continuos intraocular pressure curve even in the early stages of disease. Diabetic patients with adequate glycaemic control, exhibit maintenance of macular blood flow, macular topography and visual function following phacoemulsification.

Objective methods for anterior ocular grading

This thesis set out to develop an objective analysis programme that correlates with subjective grades but has improved sensitivity and reliability in its measures so that the possibility of early detection and reliable monitoring of changes in anterior ocular surfaces (bulbar hyperaemia, palpebral redness, palpebral roughness and corneal straining) could be increased. The sensitivity of the program was 20x greater than subjective grading by optometrists. The reliability was found to be optimal (r=1.0) with subjective grading up to 144x more variable (r=0.08). Objective measures were used to create formulae for an overall ‘objective-grade’ (per surface) equivalent to those displayed by the CCLRU or Efron scales. The correlation between the formulated objective verses subjective grades was high, with adjusted r2 up to 0.96. Determination of baseline levels of objective grade were investigated over four age groups (5-85years n= 120) so that in practice a comparison against the ‘normal limits’ could be made. Differences for bulbar hyperaemia were found between the age groups (p<0.001), and also for palpebral redness and roughness (p<0.001). The objective formulae were then applied to the investigation of diurnal variation in order to account for any change that may affect the baseline. Increases in bulbar hyperaemia and palpebral redness were found between examinations in the morning and evening. Correlation factors were recommended. The program was then applied to clinical situations in the form of a contact lens trial and an investigation into iritis and keratoconus where it successfully recognised various surface changes. This programme could become a valuable tool, greatly improving the chances of early detection of anterior ocular abnormalities, and facilitating reliable monitoring of disease progression in clinical as well as research environments.

Measurement of ocular component contributions to residual astigmatism in adult human eyes

The aim of this study was to determine whether an ophthalmophakometric technique could offer a feasible means of investigating ocular component contributions to residual astigmatism in human eyes. Current opinion was gathered on the prevalence, magnitude and source of residual astigmatism. It emerged that a comprehensive evaluation of the astigmatic contributions of the eye's internal ocular surfaces and their respective axial separations (effectivity) had not been carried out to date. An ophthalmophakometric technique was developed to measure astigmatism arising from the internal ocular components. Procedures included the measurement of refractive error (infra-red autorefractometry), anterior corneal surface power (computerised video keratography), axial distances (A-scan ultrasonography) and the powers of the posterior corneal surface in addition to both surfaces of the crystalline lens (multi-meridional still flash ophthalmophakometry). Computing schemes were developed to yield the required biometric data. These included (1) calculation of crystalline lens surface powers in the absence of Purkinje images arising from its anterior surface, (2) application of meridional analysis to derive spherocylindrical surface powers from notional powers calculated along four pre-selected meridians, (3) application of astigmatic decomposition and vergence analysis to calculate contributions to residual astigmatism of ocular components with obliquely related cylinder axes, (4) calculation of the effect of random experimental errors on the calculated ocular component data. A complete set of biometric measurements were taken from both eyes of 66 undergraduate students. Effectivity due to corneal thickness made the smallest cylinder power contribution (up to 0.25DC) to residual astigmatism followed by contributions of the anterior chamber depth (up to 0.50DC) and crystalline lens thickness (up to 1.00DC). In each case astigmatic contributions were predominantly direct. More astigmatism arose from the posterior corneal surface (up to 1.00DC) and both crystalline lens surfaces (up to 2.50DC). The astigmatic contributions of the posterior corneal and lens surfaces were found to be predominantly inverse whilst direct astigmatism arose from the anterior lens surface. Very similar results were found for right versus left eyes and males versus females. Repeatability was assessed on 20 individuals. The ophthalmophakometric method was found to be prone to considerable accumulated experimental errors. However, these errors are random in nature so that group averaged data were found to be reasonably repeatable. A further confirmatory study was carried out on 10 individuals which demonstrated that biometric measurements made with and without cycloplegia did not differ significantly.

The effect of beta-adrenergic receptor antagonists on the temporal accommodative response

In this thesis a modified Canon IR optometer was used to record static and continuous responses of accommodation during sustained visual tasks. The instrument was assessed with regard to the ocular exit pupil used, its frequency response and noise levels. Experimental work concerned essentially the temporal characteristics and neurological basis of the accommodative mechanism. In the absence of visual stimuli, the accommodative system assumes a resting or tonic accommodative (TA) position, which may be modified by periods of sustained fixation. The rate of regression from a near task to TA in darkness has exhibited differences between regression rates for enunetropes (EMMs) compared with late-onset myopes (WMs). The rate of accommodative regression from a task set at 3D above TA was examined for a group of 10 EMMs and 10 LOMs for 3 conditions: saline, timolol and betaxolol. Timolol retarded the regression to TA for a sub-group of EMMs. The patterns of regression for the remaining emmetropes mirrored that for the LOMs, the drugs showing no difference in rate of regression compared with the saline condition. This provides support for the conjecture that LOMs and certain EMMs appear to be deficient in a sympathetic inhibitory component to the ciliary muscle which may attenuate adaptational changes in tonus and which leave them susceptible to the development of LOM. It is well established that the steady-state accommodative response is characterised by temporal changes in lens power having 2 dominant frequency components: a low frequency component (LFC: < 0.6Hz) and a high frequency component (HFC: 1.0-2.2Hz). This thesis investigates various aspects of these microfluctuations of accommodation.The HFC of accommodative fluctuations was shown to be present in central and peripheral lens zones, although the magnitude of the rms of accommodative microfluctuations was found to be reduced in the lens periphery. These findings concur with the proposal that the lens capsule acts as a force distributor, transmitting the tension from the zonules evenly over the whole of the lens surface.An investigation into the correlation between arterial pulse and the HFC of accommodative fluctuations showed that the peak frequency of the HFC was governed by the arterial pulse frequency. It was proposed that the microflucutations comprised a combination of neurological control (LFC) and physiological variations (HFC).The effect of timolol maleate on the steady-state accommodative response for a group of 10 emmetropes showed that timolol reduced significantly the rms of accommodative microfluctuations in treated but not untreated eyes. Consequently, the effect was considered to be locally, rather than systemically induced.The influence of the sympathetic system on within-task measurements of accommodation was examined by recording the accommodative response of 3 subjects to a sinusoidally moving target at 6 temporal frequencies from 0.05Hz to 0.5Hz for 3 drug conditions: saline, timolol and betaxolol. Timolol caused a reduced gain for frequencies below 0.3 whereas betaxolol reduced accommodative gain for all frequencies. It was proposed that the results for timolol were consistent with temporal response characteristics of sympathetic innervation of the ciliary muscle whereas the betaxolol results were thought to be a manifestation of fatigue resulting from the CNS depressant effect of the drug.

Biometric and physiological factors in human ocular perfusion

By addressing the vascular features that characterise myopia, this thesis aims to provide an understanding of the early structural changes associated with human myopia and the progression to co-morbidity with age. This thesis addresses three main areas of study: 1. Ocular perfusion features and autoregulatory mechanisms in human myopia; 2. Choroidal thickness at the macular area of myopic eyes; 3. Effect of chronic smoking on the ocular haemodynamics and autoregulation. This thesis demonstrated a reduced resting ocular pulse amplitude and retrobulbar blood flow in human myopia, associated with an apparent oversensitivity to the vasodilatory effects of hypercapnia, which may be due to anatomical differences in the volume of the vessel beds. In young smokers, normal resting state vascular characteristics were present; however there also appeared to be increased reactivity to hypercapnia, possibly due to relative chronic hypoxia. The systemic circulation in myopes and smokers over-reacted similarly to hypercapnia suggesting that physiologic differences are not confined to the eye. Age also showed a negative effect on autoregulatory capacity in otherwise normal eyes. Collectively, these findings suggest that myopes and smokers require greater autoregulatory capacity to maintain appropriate oxygenation of retinal tissue, and since the capacity for such regulation reduces with age, these groups are at greater risk of insufficient autoregulation and relative hypoxia with age.

Ocular and systemic vascular dysfunction in neurodegenerative disease

The important role played by vascular factors in the pathogenesis of neurodegenerative disease has been increasingly realised over recent years. The nature and impact of ocular and systemic vascular dysfunction in the pathogenesis of comparable neurodegenerative diseases such as glaucoma and Alzheimer’s disease (AD) has however never been fully explored. The aim of this thesis was therefore to investigate the presence of macro- and micro-vascular alterations in both glaucoma and AD and to explore the relationships between these two chronic, slowly progressive neurodegenerative diseases. The principle sections and findings of this work were: 1. Is the eye a window to the brain? Retinal vascular dysfunction in Alzheimer’s disease · Mild newly diagnosed AD patients demonstrated ocular vascular dysfunction, in the form of an altered retinal vascular response to flicker light, which correlated with their degree of cognitive impairment. 2. Ocular and systemic vascular abnormalities in newly diagnosed normal tension glaucoma (NTG) patients · NTG patients demonstrated an altered retinal arterial constriction response to flicker light along with an increased systemic arterial stiffness and carotid artery intima-media thickness (IMT). These findings were not replicated by healthy age matched controls. 3. Ocular vascular dysregulation in AD compares to both POAG and NTG · AD patients demonstrated altered retinal arterial reactivity to flicker light which was comparable to that of POAG patients and altered baseline venous reactivity which was comparable to that of NTG patients. Neither alteration was replicated by healthy controls. 4. POAG and NTG: two separate diseases or one continuous entity? The vascular perspective · POAG and NTG patients demonstrated comparable alterations in nocturnal systolic blood pressure (SBP) variability, ocular perfusion pressure, retinal vascular reactivity, systemic arterial stiffness and carotid IMT. · Nocturnal SBP variability was found to correlate with both retinal artery baseline diameter fluctuation and carotid IMT across the glaucoma groups.

Self-assembly of trehalose molecules on a lysozyme surface: the broken glass hypothesis

To help understand how sugar interactions with proteins stabilise biomolecular structures, we compare the three main hypotheses for the phenomenon with the results of long molecular dynamics simulations on lysozyme in aqueous trehalose solution (0.75 M). We show that the water replacement and water entrapment hypotheses need not be mutually exclusive, because the trehalose molecules assemble in distinctive clusters on the surface of the protein. The flexibility of the protein backbone is reduced under the sugar patches supporting earlier findings that link reduced flexibility of the protein with its higher stability. The results explain the apparent contradiction between different experimental and theoretical results for trehalose effects on proteins.

The effect of care solutions on the bulk and surface properties of soft contact lenses

Purpose: Soft contact lenses for continuous wear require the use of cleaning regimes which utilise hydrogen peroxide systems or multipurpose cleaning solutions (MPS). The compositions of MPS are becoming increasingly complex and often include disinfectants, cleaning agents, preservatives, wetting agents, demulcents, chelating and buffering agents. Recent research on solution–lens interactions has focused on specific ocular parameters such as corneal staining. However the effect of a solution on the lens, particularly silicone hydrogel lenses, itself has received less attention. The purpose of this work was to establish and understand the effects that care solutions have on selected bulk and surface material properties. Methods: Selected bulk and surface properties of each material (etafilcon A, vifilcon A, balafilcon A, senofilcon A, lotrafilcon A and lotrafilcon B, galyfilcon A) were measured after a 24 h soak in a variety of care solutions. Additionally the lenses were soaked for 24 h in hyperosmolar (680 mOsm L-1) and hyposmolar (170 mOsm L-1) PBS. A bulk property parameter the total diameter (TD) was measured using an Optimec contact lens analyser. The surface property related CoF of soaked lenses was measured on a nano-tribometer with conditions of load 30 mN, at a distance of 20 mm and speed 30 mm/min. Results: In terms of bulk properties, change is related to the EWC of the lens, the higher the EWC of the lens the greater the TD changes. Silicone hydrogel lenses have EWCs of <47% and little or no TD changes were observed; lotrafilcon A exhibited no change irrespective of the cleaning solution. Conventional contact lenses have higher EWCs (58% for etafilcon A and 55% for vifilcon A) and the TD was seen to change to a greater extent, for example the etafilcon A material in ReNu MPS had an increase to 14.45± 0.07 mm from the cited 14.2 mm. Other lenses increased or decreased in TD depending on the solution used. The osmolarity of the solution although important is not the only factor governing change in the TD, for example soaking senofilcon A in hyperosmolar PBS (680 mOsm L-1) for 24 h increased the TD of the lens (+0.25 ± 0.07 mm), however when the same lens type was soaked for 24 h in a MPS with a lower osmolarity there was a similar effect. Biotribology measurements demonstrated that some solution–lens combinations can reduce the CoF by 55%, when compared with biotribology with the native packing solution. An increase in the CoF was observed for other solution–lens combinations. Conclusions: There is a dramatic difference in bulk and surface performance of specific lens materials with particular care solutions. Individual components of the care solutions have effects on the bulk and surface properties of contact lenses. The affects are not as great with the silicone hydrogel as compared with conventional hydrogels.

Ion interactions with the carbon nanotube surface in aqueous solutions:understanding the molecular mechanisms

We study the molecular mechanisms of alkali halide ion interactions with the single-wall carbon nanotube surface in water by means of fully atomistic molecular dynamics simulations. We focus on the basic physical-chemical principles of ion–nanotube interactions in aqueous solutions and discuss them in light of recent experimental findings on selective ion effects on carbon nanotubes.

Surface- and deep-level dissimilarity effects on social integration and individual effectiveness related outcomes in work groups:a meta-analytic integration

Prior research linking demographic (e.g., age, ethnicity/race, gender, and tenure) and underlying psychological (e.g., personality, attitudes, and values) dissimilarity variables to individual group member's work-related outcomes produced mixed and contradictory results. To account for these findings, this study develops a contingency framework and tests it using meta-analytic and structural equation modelling techniques. In line with this framework, results showed different effects of surface-level (i.e., demographic) dissimilarity and deep-level (i.e., underlying psychological) dissimilarity on social integration, and ultimately on individual effectiveness related outcomes (i.e., turnover, task, and contextual performance). Specifically, surface-level dissimilarity had a negative effect on social integration under low but not under high team interdependence. In return, social integration fully mediated the negative relationship between surface-level dissimilarity and individual effectiveness related outcomes under low interdependence. In contrast, deep-level dissimilarity had a negative effect on social integration, which was stronger under high and weaker under low team interdependence. Contrary to our predictions, social integration did not mediate the negative relationship between deep-level dissimilarity and individual effectiveness related outcomes but suppressed positive direct effects of deep-level dissimilarity on individual effectiveness related outcomes. Possible explanations for these counterintuitive findings are discussed. © 2011 The British Psychological Society.

Ocular motor triad with single vision contact lenses compared to spectacle lenses

Aim: Theoretically myopes are required to exert more accommodation and vergence when wearing single vision contact lenses compared to glasses and hypermetropes less. This study aims to quantify the effects clinically. Method: Thirty subjects (21 female, nine male, average age 21.0 ± 2.2 years) with a range of refractive errors (-7.87 D to +3.50 D) viewed in a random order, static targets at 0.1, 0.5, 1.0, 2.0, 3.0, 4.0 and 5.0 D accommodative demand that were matched for angular subtense. The subjects were fully corrected with spectacles and daily disposable contact lenses to their full prescription. Accommodation was monitored objectively with the PowerRefractor and Shin-Nippon SRW5000 and vergence and pupil size with the PowerRefractor. Results: Myopes exerted greater accommodative effort for viewing near targets with contact lenses than glasses and hypermetropes less (r2 = 0.35, p = 0.001 PowerRefractor). Myopes also exerted greater vergence effort for viewing near targets with contact lenses than glasses and hypermetropes less (r2 = 0.22, p < 0.01). Conclusion: Theoretical calculation of the accommodative and vergence requirements with glasses compared to contact lenses reflect clinical findings, although there is reasonable variability between individuals. © 2006 British Contact Lens Association.

Surface roughness after excimer laser ablation using a PMMA model:profilometry and effects on vision

PURPOSE: To show that the limited quality of surfaces produced by one model of excimer laser systems can degrade visual performance with a polymethylmethacrylate (PMMA) model. METHODS: A range of lenses of different powers was ablated in PMMA sheets using five DOS-based Nidek EC-5000 laser systems (Nidek Technologies, Gamagori, Japan) from different clinics. Surface quality was objectively assessed using profilometry. Contrast sensitivity and visual acuity were measured through the lenses when their powers were neutralized with suitable spectacle trial lenses. RESULTS: Average surface roughness was found to increase with lens power, roughness values being higher for negative lenses than for positive lenses. Losses in visual contrast sensitivity and acuity measured in two subjects were found to follow a similar pattern. Findings are similar to those previously published with other excimer laser systems. CONCLUSIONS: Levels of surface roughness produced by some laser systems may be sufficient to degrade visual performance under some circumstances.

The normal optic nerve variations in an optometric population:Possible ocular and systemic influences

Early detection of glaucoma relies on a detailed knowledge of how the normal optic nerve (ONH) varies within the population. The purpose of this study focused on two main areas; 1. To explore the optic nerve head appearance in the normal optometric population and compare the south Asian (principally Pakistani) with the European white population, correcting for possible ocular and non-ocular influences in a multiple regression model. The main findings were: • The optic discs of the South Asian (SA) and White European (WE) populations were not statistically different in size. The SA group possessed discs with increased cupping and thinner neuro-retinal rims (NRR) compared with the WE group. The SA group also demonstrated a more vertically oval shape than the WE population. These differences were significant at the p<0.01 level. • The upper limits of inter-eye asymmetry were: ≤0.2 for cup to disc area ratio, and 3mmHg for intra-ocular pressure (IOP) for both ethnic groups and this did not increase with age. IOP asymmetry did not vary with gender, ethnicity or a family history of glaucoma and was independent of ONH asymmetry. ONH and IOP asymmetry are therefore independent risk factors when screening for glaucoma for both ethnic groups. 2. To investigate the validity of the ISNT rule: inferior> superior> nasal> temporal NRR thickness in the optometric population. The main findings were: • As disc size increased the disc become rounder and less vertically oval in shape. Vertically oval discs had thicker superior and inferior NRRs and thinner nasal and temporal NRRs compared with rounder disc shapes due to cup shape being independent of disc shape. Vertically oval discs were therefore more likely to obey the ISNT rule than larger rounder discs. • The ISNT rule has a low adherence in our sample of normal eyes (5.7%). However, by removing the nasal sector to become the IST rule, 74.5% of normal eyes obeyed. SA eyes and female gender were more likely to obey the ISNT rule due to increased disc ovality. The IST rule is independent of disc shape and therefore more suitable for assessing discs from both ethnic backgrounds. Obeying the ISNT rule or IST rule was not related to disc or cup size.

Analysis of femtosecond laser surface patterning on bulk single-crystalline diamond

Preliminary work is reported on 2-D and 3-D microstructures written directly with a Yb:YAG 1026 nm femtosecond (fs) laser on bulk chemical vapour deposition (CVD) single-crystalline diamond. Smooth graphitic lines and other structures were written on the surface of a CVD diamond sample with a thickness of 0.7mm under low laser fluences. This capability opens up the opportunity for making electronic devices and micro-electromechanical structures on diamond substrates. The fabrication process was optimised through testing a range of laser energies at a 100 kHz repetition rate with sub-500fs pulses. These graphitic lines and structures have been characterised using optical microscopy, Raman spectroscopy, X-ray photoelectron spectroscopy and atomic force microscopy. Using these analysis techniques, the formation of sp2 and sp3 bonds is explored and the ratio between sp2 and sp3 bonds after fs laser patterning is quantified. We present the early findings from this study and characterise the relationship between the graphitic line formation and the different fs laser exposure conditions. © 2012 Taylor & Francis.