Predicting changes in measured introcular pressure with non-contact tonometry after LASIK

Purpose: Optometrists are becoming more integrally involved in the diagnosis of and care for glaucoma patients in the UK. The correlation of apparent change in non contact tonometry (NCT) IOP measurement and change in other ocular parameters such as refractive error, corneal curvature, corneal thickness and treatment zone size (data available to optometrists after LASIK) would facilitate care of these patients. Setting: A UK Laser Eye Clinic. Methods: This is a retrospective study study of 200 sequential eyes with myopia with or without astigmatism which underwent LASIK using a Hansatome and an Alcon LADARvision 4000 excimer laser. Refraction keratometry, pachymetry and NCT IOP mesurements were taken before treatmebnt and agian 3 months after treatment. The relationship between these variables anfd teh treatment zones were studied using stepwise multiple regression analysis. Results: There was a mean difference of 5.54mmHg comnparing pre and postoperative NCT IOP. IOP change correlates with refractive error change (P < 0.001), preoperative corneal thickness (P < 0.001) and treatment zone size (P = 0.047). Preoperative corneal thickness correlates with preoperative IOP (P < 0.001) and postoperative IOP (P < 0.001). Using these correlations, the measured difference in NCT IIOP can be predicted preoperatively or postoperatively using derived equations.Conclusion: There is a significant reduction in measured NCT IOP after LASIK. The amount of reduction can be calculated using data acquired by optometrists. This is helpful for opthalmologists and optometrists who co-manage glaucoma patients who have had LASIK or with glaucoma pateints who are consideraing having LASIK.

A new non-contact optical device for ocular biometry

Background: A new commercially available device (IOLMaster, Zeiss Instruments) provides high resolution non-contact measurements of axial length (using partial coherent interferometry), anterior chamber depth, and corneal radius (using image analysis). The study evaluates the validity and repeatability of these measurements and compares the findings with those obtained from instrumentation currently used in clinical practice. Method: Measurements were taken on 52 subjects (104 eyes) aged 18-40 years with a range of mean spherical refractive error from +7.0 D to -9.50 D. IOLMaster measurements of anterior chamber depth and axial length were compared with A-scan applanation ultrasonography (Storz Omega) and those for corneal radius with a Javal-Schiötz keratometer (Topcon) and an EyeSys corneal videokeratoscope. Results: Axial length: the difference between IOLMaster and ultrasound measures was insignificant (0.02 (SD 0.32) mm, p = 0.47) with no bias across the range sampled (22.40-27.99 mm). Anterior chamber depth: significantly shorter depths than ultrasound were found with the IOLMaster (-0.06 (0.25) mm, p <0.02) with no bias across the range sampled (2.85-4.40 mm). Corneal radius: IOLMaster measurements matched more closely those of the keratometer than those of the videokeratoscope (mean difference -0.03 v -0.06 mm respectively), but were more variable (95% confidence 0.13 v 0.07 mm). The repeatability of all the above IOLMaster biometric measures was found to be of a high order with no significant bias across the measurement ranges sampled. Conclusions: The validity and repeatability of measurements provided by the IOLMaster will augment future studies in ocular biometry.

A novel, dynamic, in vivo, non-contact method of measuring oxygen depletion rate of the anterior eye

Despite the importance of oxygen measurements, techniques have been limited by their invasive nature and small corneal area of assessment. The aim of this study was to assess a non-contact way of measuring oxygen uptake of the whole anterior eye.

Statnote 23: Non-parametric analysis of variance (ANOVA)

To carry out an analysis of variance, several assumptions are made about the nature of the experimental data which have to be at least approximately true for the tests to be valid. One of the most important of these assumptions is that a measured quantity must be a parametric variable, i.e., a member of a normally distributed population. If the data are not normally distributed, then one method of approach is to transform the data to a different scale so that the new variable is more likely to be normally distributed. An alternative method, however, is to use a non-parametric analysis of variance. There are a limited number of such tests available but two useful tests are described in this Statnote, viz., the Kruskal-Wallis test and Friedmann’s analysis of variance.

The effect of corruption on FDI:a parametric and non-parametric analysis

This paper analyses the effect of corruption on Multinational Enterprises' (MNEs) incentives to undertake FDI in a particular country. We contribute to the existing literature by modelling the relationship between corruption and FDI using both parametric and non-parametric methods. We report that the impact of corruption on FDI stock is different for the different quantiles of the FDI stock distribution. This is a characteristic that could not be captured in previous studies which used only parametric methods. After controlling for the location selection process of MNEs and other host country characteristics, the result from both parametric and non-parametric analyses offer some support for the ‘helping-hand’ role of corruption.

Generation of primary hepatocyte microarrays by piezoelectric printing

We demonstrate a single-step method for the generation of collagen and poly-l-Lysine (PLL) micropatterns on a poly(ethylene glycol) (PEG) functionalized glass surface for cell based assays. The method involves establishing a reliable silanization method to create an effective non-adhesive PEG layer on glass that inhibits cell attachment, followed by the spotting of collagen or PLL solutions using non-contact piezoelectric printing. We show for the first time that the spotted protein micropatterns remain stable on the PEG surface even after extensive washing, thus significantly simplifying protein pattern formation. We found that adherence and spreading of NIH-3T3 fibroblasts was confined to PLL and collagen areas of the micropatterns. In contrast, primary rat hepatocytes adhered and spread only on collagen micropatterns, where they formed uniform, well defined functionally active cell arrays. The differing affinity of hepatocytes and NIH-3T3 fibroblasts for collagen and PLL patterns was used to develop a simple technique for creating a co-culture of the two cell types. This has the potential to form structured arrays that mimic the in vivo hepatic environment and is easily integrated within a miniaturized analytical platform for developing high throughput toxicity analysis in vitro.

The tear film and contact lens wear

Contact lenses have become a popular method of vision correction for millions of people globally. As with all devices designed for use within the body, interactions occur between the implanted material and the surrounding biological fluid. A common complaint of lens wearers is that they often experience symptoms of dry eye whilst wearing lenses. This sensation is often heightened towards the end of the day. Through the course of this study, various analytical techniques have been utilised including one dimensional electrophoresis and Western Blotting to study the protein profiles of tear samples. By studying the tears of non-contact lens wearers, it was possible to analyse what could be considered normal, healthy, individuals. A clinical study was also undertaken which followed a population of individuals from the neophyte stage to one whereby they were accustomed lens wearers. Tears were monitored at regular intervals throughout the course of this study and worn contact lenses were also analysed for proteins that had been deposited both on and within the lens. Contact lenses disrupt the tear film in a physical manner by their very presence. They are also thought to cause the normal protein profile to deviate from what would be considered normal. The tear film deposits proteins and lipids onto and within the lens. The lens may therefore be depriving the tear film of certain necessary components. The ultimate aim of this thesis was to discover how, and to what extent, lenses affected tear proteins and if there were any proteins in the tear fluid that had the potential to be used as biochemical markers. Should this be achievable it may be possible to identify those individuals who were more likely to become intolerant lens wearers. This study followed the changes taking place to the tear film as an effect of wearing contact lenses. Twenty-eight patients wore two different types of silicone hydrogel lenses in both a daily wear and a continuous wear regime. The tear protein profiles of the lens-wearers were compared with a control group of non-lens wearing individuals. The considerable amount of data that was generated enabled the clearly observable changes to the four main tear proteins to be monitored.

Ocular response to silicone-hydrogel contact lenses

The thesis investigates the ocular response to silicone-hydrogel (SiH) contact lens wear, a relatively new contact lens material that has a higher modulus of rigidity and different surface coating than used in conventional hydrogel materials. The properties of SiH materials differ significantly from conventional hydrogels and, using subjective and objective means of assessment, the thesis examines how these properties affect reflection and biometry, ocular physiology, tear film characteristics, symptomatology, adverse events and complications. A range of standard and newly designed investigative techniques were employed, and latter involving novel imaging techniques, for the objective assessment of physiological changes which occur with contact lens wear. The study is the first to combine these techniques with biochemical analyses of the tear film composition. Forty-seven subjects were fitted with SiH lenses and randomly allocated to one of the two materials currently on the market (Lotrafilcon A or Balafilcon A) on an either daily or continuous wear basis. An additional control group of 14 age-matched non-contact lens wearers were monitored over the same period. Measurements were taken before and 1, 3, 6, 12 and 18 months after initial fitting. The findings reported in this thesis will enable contact lens practitioners and manufacturers to understand further the optical, physiological and biochemical nature of the ocular response to SiH contact lenses and hence facilitate the development of this important generation of contact lens material.

Some clinical aspects of the eye in extended contact lens wear

The limbal vascular response to extended contact lens wear was examined in a group comparative study initially intended to last eighteen months. After six months all patients wearing contact lenses had presented with micro-epithelial cysts. This unanticipated occurrence of the micro-epithelial-cysts necessitated termination of the study, and limited the quantity of data collected. However, sufficient results were available to allow a limited description of •the vascular response to this form of contact lens wear. Interpretations of the date collected ore discussed in relation to suggested vasostimulating factors in the cornea. The micro-epithelial cysts observed after extended wear were classified and their rate of recovery recorded. A further clinical study was undertaken to observe cysts in both contact lens - and non contact lens-wearing eyes. Cysts were observed in every category of patient, although the characteristic patterns varied. These observations of micro-epithelial cysts are discussed with respect to the aetiopathogeneses of corneal epithelial cystic disorders. Subsequently, attempts were made to induce cysts in rabbit corneae by extended contact lens wear. Clinical observations revealed cyst-like appearances. Histological sections did not contain cysts but did exhibit signs characteristic •of cystic disorders of the corneal epithelium. In general, the results from the study indicate that extended wear is subjectively acceptable to contact lens wearers. However, the objective findings of significant vascular changes, micro-epithelial cysts and cases of acute red eye response cast considerable doubt on the recommendation of extended wear contact lenses for purely cosmetic applications.

Epidemiology of myopia in a United Kingdom urban child population

The Aston Eye Study (AES) was instigated in October 2005 to determine the distribution of refractive error and associated ocular biometry in a sample of UK urban school children. The AES is the first study to compare outcome measures separately in White, South Asian and Black children. Children were selected from two age groups (Year 2 children aged 6/7 years, Year8 children aged 12/13 years of age) using random cluster sampling of schools in Birmingham, West Midlands UK. To date, the AES has examined 598 children (302 Year 2,296 Year 8). Using open-field cycloplegic autorefraction, the overall prevalence of myopia (=-0.50D SER in either eye) determined was 19.6%, with a higher prevalence in older (29.4%) compared to younger (9.9%) children (p<0.001). Using multiple logistic regression models, the risk of myopia was higher in Year 8 South Asian compared to White children and higher in children attending grammar schools relative to comprehensive schools. In addition, the prevalence of uncorrected ametropia was found to be high (Year 8: 12.84%, Year 2: 15.23%), which will be of concern to bodies responsible for the implementation of school vision screening strategies. Biometric data using non-contact partial coherence interferometry revealed a contributory effect of axial length (AL) and central corneal radius (CR) on myopic refraction, resulting in a strong coefficient of determination of the AL/CR ratio on refractive error. Ocular biometric measures did not vary significantly as a function of ethnicity, suggesting a greater miscorrelation of components in susceptible ethnic groups to account for their higher myopia prevalence. Corneal radius was found to be steeper in myopes in both age groups, but was found to flatten with increasing axial length. Due to the inextricable link between myopia and axial elongation, the paradoxical finding of the cornea demands further longitudinal investigation, particularly in relation to myopia onset. Questionnaire analysis revealed a history of myopia in parents and siblings to be significantly associated with myopia in Year 8 children, with a dose-dependent rise in the odds ratio of myopia evident with increasing number of myopic parents. By classifying socioeconomic status (SES) using Index of Multiple Deprivation values, it was found that Year 8 children from moderately deprived backgrounds were more at risk of myopia compared with children located at both extremities of the deprivation spectrum. However, the main effect of SES weakened following multivariate analysis, with South Asian ethnicity and grammar schooling remaining associated with Year 8 myopia after adjustment.

Contact lenses and sport

Contact lenses seem to be the ideal method of vision correction for ametropic people who participate in sporting activities. This thesis sets out to evaluate the viewpoint of the optometric professional and that of the patient on the use of contact lenses in sport and to establish if education is needed within this area. It also aims to provide some scientific evidence on the effect of exercise on the physiology of the cornea with and without contact lenses. Silicone hydrogel contact lenses have previously been suggested to impede heat dissipation from the cornea compared to mid water hydrogels. This was further demonstrated with exercise. The physiological integrity of the cornea is dependant on the amount of oxygen available to its surfaces. Contact lenses can disrupt the diffusion of oxygen to the cornea. Previous methods of measuring the oxygen consumption of the cornea have been limited by their invasive nature and assessment of only a small surface area of the cornea. They are not suitable to measure corneal oxygen consumption during exercise with and without contact lenses. A new method needed to be established. This was achieved by designing a novel method by the use of an oxygen sensor inside an airtight goggle using dynamic quenching of luminescence method. This established a non-contact way of measuring the effect oxygen uptake with and without contact lenses in vivo, allowing the contact lens to be undisturbed in their natural environment. The new method differentiated between the closed-eye and the open-eye condition with a good within-visit repeatability. It also illustrated that the cornea utilises oxygen at a faster rate during controlled aerobic exercise at moderate intensity. New contact lenses are available specifically for sport, these claim to reduce glare and increase contrast for daylight outdoor sports. However, visual benefits of these types of contact lenses cannot be measured easily in an indoor clinical environment, such as the optometric practice. To demonstrate any potential benefits of these lenses emulation of them should be conducted outdoors.

Accommodation and intraocular pressure

The relationship between accommodation and intraocular pressure (lOP) has not been addressed as a research question for over 20 years, when measurement of both of these parameters was less advanced than today. Hence the central aim of this thesis was to evaluate the effects of accommodation on lOP. The instrument of choice throughout this thesis was the Pulsair EasyEye non-contact tonometer (NCT) due principally to its slim-line design which allowed the measurement of lOP in one eye and simultaneous stimulation of accommodation in the other eye. A second reason for using the Pulsair EasyEye NCT was that through collaboration with the manufacturers (Keeler, UK) the instrument's operational technology was made accessible. Hence, the principle components underpinning non-contact lOP measures of 0.1mmHg resolution (an order of magnitude greater than other methods) were made available. The relationship between the pressure-output and corneal response has been termed the pressure-response relationship, aspects of which have been shown to be related to ocular biometric parameters. Further, analysis of the components of the pressure-response relationship together with high-speed photography of the cornea during tonometry has enhanced our understanding of the derivation of an lOP measure with the Pulsair EasyEye NCT. The NCT samples the corneal response to the pressure pulse over a 19 ms cycle photoelectronically, but computes the subject's lOP using the data collected in the first 2.34 ms. The relatively instantaneous nature of the lOP measurement renders the measures susceptible to variations in the steady-state lOP caused by the respiratory and cardiac cycles. As such, the variance associated with these cycles was minimised by synchronising the lOP measures with the cardiac trace and maintaining a constant pace respiratory cycle at 15 breathes/minute. It is apparent that synchronising the lOP measures with the peak, middle or trough of the cardiac trace significantly reduced the spread of consecutive measures. Of the 3 locations investigated, synchronisation with the middle location demonstrated the least variance (coeflicient of variation = 9.1%) and a strong correlation (r = 0.90, p = <0.001) with lOP values obtained with Goldmann contact tonometry (n = 50). Accordingly lOP measures synchronised with the middle location of the cardiac cycle were taken in the RE while the LE fixated low (L; zero D), intermediate (I; 1.50 D) and high (H; 4 D) accommodation targets, Quasi-continuous measures of accommodation responses were obtained during the lOP measurement period using the portable infrared Grand Seiko FR-5000 autorefractor. The lOP reduced between L and I accommodative levels by approximately 0.61 mmHg (p <0.00 I). No significant reduction in IOP between L and H accommodation levels was elicited (p = 0.65) (n = 40). The relationship between accommodation and lOP was characterised by substantial inter-subject variations. Myopes demonstrated a tendency to show a reduction in IOP with accommodation which was significant only with I accommodation levels when measured with the NCT (r = 0.50, p = 0.01). However, the relationship between myopia and lOP change with accommodation reached significance for both I (r = 0.61, p= 0.003) and H (r = 0.531, p= 0.0 1) accommodation levels when measured with the Ocular blood Flow Analyser (OBFA). Investigation of the effects of accommodation on the parameters measured by the OBFA demonstrated that with H accommodation levels the pulse amplitude (PA) and pulse rate (PR) responses differed between myopes and emmetropes (PA: p = 0.03; PR: p = 0.004). As thc axial length increased there was a tendency for the pulsatile ocular blood flow (POBF) to reduce with accommodation, which was significant only with H accommodation levels (r = 0.38, p = 0.02). It is proposed that emmetropes arc able to regulate the POBF responses to changes in ocular perfusion pressure caused by changes in lOP with I (r = 0.77, p <0.001) and H (r = 0.73, p = 0.001) accommodation levels. However, thc relationship between lOP and POBF changes in the myopes was not correlated for both I (r = 0.33, p = 0.20) and H (r = 0.05, p = 0.85) accommodation levels. The thesis presents new data on the relationships between accommodation, lOP and parameters of the OBFA,: and provides evidence for possible lOP and choroidal blood flow regulatory mechanisms. Further the data highlight possible deficits in the vascular regulation of the myopic eye during accommodation, which may play a putative role in the aetiology of myopia development.