Purpose To examine soft contact lens fitting characteristics using anterior segment imaging techniques and comfort. The specific aims of each chapter are as follows: Chapter 2: To calibrate the new ZEISS VisanteTM anterior segment optical coherence tomographer (OCT) using references with known physical thickness and refractive index equal to the human cornea and to compare the Visante measures to those from a previous generation OCT (Zeiss-Humphrey OCT II). Chapter 3: The first purpose of this study was to measure the repeatability of the Visante TM OCT in a normal sample. The second was to compare corneal thickness measured with the Visante TM OCT to the Zeiss-Humphrey OCT II (model II, Carl Zeiss Meditec, Jena Germany) adapted for anterior segment imaging and to the Orbscan II TM (Bausch and Lomb, Rochester New York). Chapter 4: Conjunctival displacement observed with the edges of the contact lens, when imaged may be real or may be an artefact of all OCT imagers. A continuous surface appears displaced when the refractive index of the leading medium changes at the edge of a contact lens. To examine this effect, edges of the contact lenses were imaged on a continuous surface using the UHR-OCT. Contact lens edges on the human conjunctival tissue were also imaged to see if the lens indentation on the conjunctival tissue is real or an artefact at the edge of the lens. Chapter 5: The main purpose of this study was to determine if we can predict end of the day discomfort and dryness using clinical predictive variables. The second purpose of the study was to determine if there was any relationship between lens fitting characteristics and clinical complications and especially to the superior cornea and conjunctiva with a dispensing clinical trial. Methods Chapter 2: Twenty two semi-rigid lenses of specified thicknesses were manufactured using a material with refractive index of 1.376. Central thickness of these lenses was measured using VisanteTM OCT and Zeiss-Humphrey OCT II (Zeiss, Germany). Two data sets consisting of nominal measures (with a standard pachymeter of the lenses and one obtained using a digital micrometer) were used as references. Regression equations between the physical and optical (OCT) measures were derived to calibrate the devices. Chapter 3: Fifteen healthy participants were recruited. At the Day 1 visit the epithelial and total corneal thickness, across the central 10mm of the horizontal meridian were measured using the OCT II and the Visante TM OCT. Only total corneal thickness across the central 10mm of the horizontal meridian was measured using the Orbscan II. The order of these measurements was randomized. These measurements were repeated on Day 2. Each individual measurement was repeated three times and averaged to give a single result. Chapter 4: (2-D) Images of the edges of marketed silicone hydrogel and hydrogel lenses with refractive indices (n) ranging from 1.41-1.51 were taken placing them concave side down on a continuous surface. Five images for each lens were taken using a UHR-OCT system, operating at 1060 nm with ~3.2um (axial) and 10μm (lateral) resolution at the rate of 75,000 A-scans/s. The displacement of the glass slide beneath the lens edge was measured using Image J. Chapter 5: Thirty participants (neophytes) were included in the study and the four lenses (Acuvue Advance 8.3, Acuvue Advance 8.7, Pure Vision 8.3, and Pure Vision 8.6) were randomly assigned for each eye. The lenses were worn for a period of two weeks on a daily wear basis for 8 to 10hrs per day. Lens performance was monitored over the 2week period. Assessment of subjective comfort was made using visual analogue scales. Total corneal and epithelium thickness was measured using the Visante OCT, the lens edge profiles of the contact lenses were observed using the ultra-high resolution OCT and the conjunctival epithelial thinning was measured using the RTVue OCT. Conjunctival blood velocity was measured at the baseline and 2 week visit using a high magnification camera. Results Chapter 2: Before calibration, repeated measures ANOVA showed that there were significant differences between the mean lens thicknesses from each of the measurement methods (p<0.05), where Visante measurements were significantly different from the other three (OCT II, MG and OP) methods (p<0.05). Visante thickness was significantly higher than the microgauge measures (453±37.6 µm compared to 445.1±38.2 µm) and the OCT II was significantly lower (424.5±36.1 µm both, p<0.05). After calibration using the regression equations between the physical and optical measurements, there were no differences between OCT II and Visante OCT (p<0.05). Chapter 3: Mean central corneal and epithelial thickness using the Visante™ OCT after calibration at the apex of the cornea was 536± 27 µm (range, 563-509 µm) and 55± 2.3 µm (range, 57.3-52.7 µm), respectively. The mean corneal and epithelial thickness using OCT II at the apex was 520±25µm and 56±4.9 µm, respectively. The mean of total corneal thickness measured with the Orbscan II was 609±29µm. Visante OCT was the most repeatable for test-retest at the apex, nasal and temporal quadrants of the cornea compared to OCT II and Orbscan II. COR’s of Visante OCT ranged from ±7.71µm to ±8.98µm for total corneal thickness and ± 8.72 µm to ± 9.92 µm for epithelial thickness. CCC’s with Visante OCT were high for total corneal thickness for test-retest differences ranging from 0.97 to 0.99, CCC’s for epithelial thickness showed moderate concordance for both the instruments. Chapter 4: Results showed that artefactual displacement of the contact lens edge was observed when the lenses were imaged on the glass reference sphere, custom made rigid contact lenses (1.376) and on the conjunctival tissue. The displacement measured on the conjunctival tissue ranged from 7.0±0.86 µm for the Air Optix Night and Day to 17.4±0.22 µm for the Acuvue Advance contact lenses. The range of displacement with the soft lens edges imaged on the rigid contact lens was from 5.51±0.03 µm to 9.72±0.12 µm. Chapter 5: The lenses with the steepest sag (Acuvue Advance 8.3, Pure Vision 8.3) resulted not only with the tightest fit, but with compromise to the superior conjunctiva. This was especially seen with the Acuvue Advance lenses. The steeper lenses caused more total corneal swelling, superior epithelial thinning, mechanical compression of conjunctiva, conjunctival staining, bulbar hyperemia, conjunctival indentation and reduced blood flow at the lens edge. Not many associations were observed between baseline clinical and 2 weeks sensory variables. However, significant associations were observed when comparing the baseline clinical variables to end of the day sensory variables. Baseline clinical variables compared to 2 week clinical variables also showed significant correlations. Conclusions Chapter 2: Using reference lenses with refractive index of the cornea (1.376) allows rapid and simple calibration and cross calibration of instruments for measuring the corneal thickness. The Visante and OCT II do not produce measurements that are equal to physical references with refractive index equal to the human cornea. Chapter 3: There is good repeatability of corneal and epithelial thickness using each OCT for test-retest differences compared to the between instruments repeatability. Measurements of epithelial thickness are less repeatable compared to the total corneal thickness for the instruments used in the study. Chapter 4: When contact lenses are imaged in-situ using UHR-OCT the conjunctival tissue appeared displaced. This experiment indicates that this displacement is an artefact of all OCT imagers since a continuous surface (glass slide) was optically displaced indicating that the displacement that is observed is a function of the refractive index change and also the thickness of the contact lens edges. Chapter 5: Discomfort is a complex issue to resolve since it appears to be related to ocular factors such as the corneal and conjunctival topography and sagittal depth; to lens factors that is 1) how the sag depth of the lenses relate to the corneal/conjunctival shape and depth and therefore how well it moves on the eye. 2) Also with the lens material; whether they are high or low modulus, low or high water content, dehydration properties, wetting agents used and its resistance to deposits, lens edge profile and thickness and its interaction with the upper eyelid.

Purpose: An important challenge for eye care practitioners is meeting the needs of an ever-increasing elderly population. Standard vision tests are inadequate for determining performance in real life situations. One test that was developed to address this issue is the Attended Field of View (AFOV) test (Coeckelbergh et al, 2004). This test was designed to assess the functional field of view when people are allowed to make habitual head and eye movements. The original AFOV test is no longer available. This research seeks to develop a replacement AFOV test and to demonstrate its reliability as an assessment tool. Methods: Two groups of participants were recruited. The first group consisted of seven participants between the ages of 15-41 years. The second group consisted of seven participants between the ages of 59–79 years. All subjects had visual acuities equal or better than 20/25 and no history of visual field loss. A computer-generated display was observed from a 60cm distance. The display consisted of 24 white circles on a gray background and one open circle (target). The circles were organized with one circle in the centre and eight located radially at three eccentricities (4, 8, and 12 degrees). Participants were required to locate the target circle and identify the gap direction. A response was considered correct when both the location and gap direction were accurate. Using a weighted staircase method based on presentation time each location was evaluated independently. Viewing efficiency [log (1/threshold presentation time)] was obtained for each location. The data was analyzed using repeated measures ANOVA. Results: A comparison of viewing efficiency for the two age groups demonstrates that viewing efficiency is consistently lower for the older group at all three visits. The main effect of age was observed (F1,12=25.842;p=0.000). In the older group, a significant difference was found between the second and third visits. This difference was not found in the younger group. A main effect of eccentricity was found in both groups (F2,36=30.84;p<0.000), but no interaction was observed between eccentricity and group (F2,36=0.42;p=0.662). Viewing efficiency values in the older group were lower in all directions (main effect of age) (F1,96=150.36;p<0.000). Directional variations in viewing efficiency were observed showing higher values in the horizontal axes (directions Right and Left) than along the vertical axes (directions Up and Down) in both groups. A comparison of superior and inferior hemifield data shows consistent differences for both age groups. The superior hemifield (average of directions located superiorly to the horizontal axis) demonstrate higher viewing efficiency values (better performance) than the inferior hemifield. Conclusions: The use of the new AFOV test requires a practice time before its use in order to avoid the confound of a learning effect, but subsequent data is reliable in young people. The learning effect was more significant in older people and for this reason the use of the test should be preceded by a longer practice session in this population. When interpreting the results of this test one must account for eccentricity, direction, and age.

Purpose Early detection of abnormal visual acuity (VA) is crucial in the identification and management of ocular and visual abnormalities in infants. Currently, the Teller Acuity Cards (TACs) are considered the gold standard for clinical testing and are effective in obtaining a quick estimate of an infant’s VA, but they have certain drawbacks. They rely on a subjective assessment of the baby’s looking behavior. Despite this, TACs have been found to have good validity and repeatability. The current study investigates a new method to objectively assess visual acuity in infants, which is uses a video gaze tracker (GT) and computer-generated stimuli, developed in the lab of M. Eizenman at the University of Toronto. The purpose was to validate this method in adults and infants against current clinical VA tests. Visual scanning patterns were measured by the GT system that requires minimal subject cooperation in adult and infant populations. The targets were judged as seen when the relative fixation time on the grating exceeded a pre-determined threshold, as compared to the fixation time on the luminance-matched background. Methods Experiment 1: In 15 uncorrected myopic adults, binocular grating VA was measured. The targets were square-wave gratings of spatial frequency ranging from 2.3 to 37 cpd presented randomly in one of four positions on the screen. There were 6 objective protocols (in which VA was judged by fixations). The subjects were naïve, as the only instruction given to the participants was to look towards the screen. The experimenter, who presented the gratings also acted as an observer by making judgments of seen/not seen responses using the objective information provided by the software. Objective GT VA was compared with VA measured with subjective responses using the same stimuli and with Teller Acuity Cards (TACs). Experiment 2: Binocular grating VA for horizontal gratings was measured in 20 typically-developing infants aged 3 to 12 months. Spatial frequency ranged from 0.32 to 42 cpd and VA was measured on two visits with both the GT and TACs. A staircase protocol was used to obtain the VA threshold in the GT. The experimenter controlled the staircase method and an observer used the objective information of visual fixations using the software to judge if the grating was seen or not. Video cartoons were shown between stimulus presentations to keep the infant’s attention towards the screen. VA was also measured with the TACs held in the vertical orientation, so that the gratings were horizontal, similar to the GT method. A TAC stage was specially designed with a vertical slot in which the cards could be presented. The observer was masked regarding the participant’s age and the starting spatial frequency. The study co-ordinator determined the choice of the start card which was randomized between participants so as to give an equal number of participants with each start card. The same start card was used for the second session of each infant. The threshold was defined as the highest spatial frequency for which the infant gave a clear, correct look and an unclear/inconsistent look for the next higher level. The observer, who was masked regarding the absolute spatial frequency, increased or decreased the spatial frequency until this threshold was determined. Results Experiment 1: The mean age of participants in the adult study was 28.47±7.93 yrs and their mean uncorrected logMAR acuity was 0.9±0.2. There was no obvious difference among the mean acuities obtained by 6 objective GT protocols, the subjective GT protocol and the TACs. The GT showed agreement of 93% and 100 % within half an octave compared with the subjective protocol and TACs (horizontal gratings) respectively. There was 100% agreement within 1 octave of the objective GT with both the subjective protocol and the TACs (horizontal gratings). The objective gaze tracker VA showed significant correlation with uncorrected refractive error (r =0.87, p < 0.001). Experiment 2: The mean age of participants was 7.9±2.5 months. In both visits, the testability of the TACs was 100% across all infants. GT had 100% testability on the first visit and 95% testability on the second visit. The mean TAC acuity over two visits for all the infants was 0.7±0.23 log cycles per degree, while the mean log GT acuity over two visits was 0.86±0.30. Infant GT VA acuity estimates were within 1 octave of the TACs 90% and 79% of the time for the first and second visit respectively, while GT VA estimates were within half octave of the TACs 63.2% and 47% of the time for the first and second visit respectively. Eighty-seven percent of the GT VAs and 72.5% of TACs were within one octave of the mean age norms, although on average the GT gave better acuities than the TACs. There was an increase in GT VA with increasing age (r=0.80, p<0.005 for the first visit and r=0.77, p<0.005 for the second visit). Both the TACs and the GT had repeatability of 89.5% within 1 octave between visits and 84.2% and 79% within half octave between visits respectively. Conclusions In adults, the gaze tracker gave VA thresholds which were equivalent to the TACs and were not significantly different from subjectively determined grating VA. The agreement of the GT with TACs in infants and with norms in the infant literature established good validity for the GT. Finally, the significant correlation with age confirmed the validity of the measurements of the gaze tracker. The repeatability of the gaze tracker was similar to that of the TACs, demonstrating the quality usefulness of the test. These results demonstrate the potential for an automated test of infant visual acuity, which could be a powerful and useful tool for visual acuity assessment in infants and other population groups who cannot respond verbally. The staircase protocol established in the study could be fully automated in an objective version of the test. The raw data of eye movements obtained in this study such as the pattern of first fixations, time taken for first fixations, time spent fixing the stimulus, typical stimulus duration and time between presentations could be used to develop algorithms for fully automated testing of VA in infants.

Optic nerve section (ONS) is an experimental model for damage of the optic nerve associated with diseases such as glaucoma and optic neuritis. Damage to the optic nerve causes loss of retinal ganglion cells that are attached, once the cells are damaged, they are not typically replaced. Recently, Fischer and Reh (2003) found that Müller glia have the potential to adopt phenotypes and functional capabilities similar to those of retinal progenitors, a potential source of retinal regeneration. In the chick, when the specific retinal cells are targeted for damage by chemotoxins, there is widespread apoptosis but also mitotically active cells that label with retinal progenitor markers. Fischer and Reh (2002) also discovered that the combination of growth factors FGF2 and insulin is capable of stimulating the regenerative response of the Müller glia to retinal progenitor cells in chick eyes. This study was conducted to analyse damage to the ganglion cells by optic nerve section in chicks to determine the effect of age on the cell death timeline, the proliferative qualities of the retina and to see if injections of growth factors had the ability to increase the proliferation. Histological methods were used to analyse cellular changes and ultrasound to monitor eye growth. Apoptotic activity preceded retinal thinning and ganglion cell loss, indicating that ONS-related cell death is mediated at least in part by apoptotic mechanisms and age did not affect the time course, although, age did affect the eye growth changes, which may be attributed to the plasticity of the younger eyes. ONS damage elicited proliferative activity in the retina as did growth factor injections alone. The combination of ONS damage and growth factor injections increased the proliferative activity and the overall total number of cells in the ganglion cell layer. These findings can potentially lead to the development of therapeutic strategies for the preservation or restoration of retinal cells in diseased eyes.

Accommodation and vergence are two interacting ocular motor systems that function to maintain clear and single vision across a wide range of distances. Sustained fixation results in the adaptation of these ocular motor systems and has been widely investigated in adults but not in children. Moreover, limited reports have measured adaptation to disparities induced by ophthalmic lenses. This thesis used near addition lenses as a means to investigate binocular adaptation in children. The specific aims of this thesis were three-fold. First, the thesis aimed to gain insight into the mechanism of changes to accommodation and vergence during binocular adaptation in children. The second objective was to determine the role of vergence-bias category (eso/exo/normals) on adaptation. Lastly, this thesis evaluated the influence of myopia on binocular adaptation. Thirty- eight myopic and 38 emmetropic children between 7-14 years of age were examined for the purpose of this thesis. A series of studies were performed to evaluate adaptation using varying demands for accommodation and vergence, stimulated by binocular fixation at near (33 cm), through the addition of +2D and -2D over corrective lenses (closed loop accommodation) and using 10 base-out prisms (open-loop accommodation at 4M). In each closed-loop condition, measures of binocular and monocular accommodation (PowerRefractor, Multichannel systems) and near phoria (modified Thorington technique) were recorded at frequent intervals when children binocularly fixated a high contrast near target (33 cm) for 20 min. For the open-loop condition (obtained using 0.5 mm pinhole pupils), binocular accommodation and tonic vergence (distance heterophoria through pinhole pupils) were determined at frequent intervals when binocular fixation was sustained at 4M for 20 min. For all conditions, tonic accommodation was measured before and after the near task to measure accommodative adaptation. The results of this thesis make three major contributions to the literature. First, it outlines that the addition of +2D and -2D lenses alters both accommodation and near phoria during sustained binocular fixation, which can be explained based on the models of accommodation and vergence. Second, it shows that the direction of phoria influences the pattern of binocular vs. monocular accommodation in closed-loop conditions and alters the degree of vergence adaptation in both closed and open-loop accommodation. These changes have been primarily attributed to the varying demands on fusional vergence. Lastly, this thesis demonstrates that myopic children show reduced vergence adaptation when fusional convergence was initiated through plus adds or base-out prisms but not when fusional divergence was initiated through minus addition lenses. Further, myopic children also showed variations in other ocular motor parameters such as higher accommodative lags, greater variability of accommodative response, larger accommodative after-effects, and higher AV/A ratios compared to emmetropes. Consistent with the models of accommodation and vergence, the thesis highlights that it is necessary to measure changes to both accommodation and vergence when evaluating the response of the ocular motor system. The direction of phoria and type of refractive error play a significant role in determining binocular adaptation in children. Future studies should differentiate these parameters when evaluating adaptation of the ocular motor system.

Purpose: This is a pilot study to investigate gaze strategies for coping with glare when performing a simple visual task under intense contra light viewing conditions. Method: Twenty-four normally sighted participants were recruited for this study. They consisted of a young subgroup (n=12), aged 21-29 (mean = 25.3 ± 2.5), and an older subgroup (n=12), aged 51-71 (mean = 57.3 ± 6.1). Visual acuity (VA) and Brightness Acuity testing (BAT) were used to assess central vision. Participants were required to locate and approach (from 15m) a small platform that was contra lit by a powerful light source. Upon arrival at the platform, participants were required to insert a small ball into a similarly sized receptacle. An ASL Mobile Eye (Bedford, MA) eye tracker was used to monitor gaze position throughout until the task was completed. Scene and pupil videos were recorded for each participant and analyzed frame by frame to locate the participant’s eye movements. Results: Two participants (one from each subgroup) adopted aversion gaze strategies wherein they avoided looking at the contra lit task for more than 50% of the task completion time. For the remainder of the experimental trial, these two participants were either looking toward the glare source or blinking. The other twenty-two participants opted to endure the contra light condition by gazing directly into the glare for the majority of the task completion time. An individual t-test between the younger iv subgroup’s BA scores vs. the older subgroup’s BA scores was statistically significant (p<0.05). Significantly poorer BAT scores were found in the older subgroup, however, individual participant’s BAT scores did not necessarily predict the ability to cope with a contra lit glare source. Although, statistically significant differences were not found between the two subgroups when examining their VA and length of time to complete the course, a trend was found, as the older subgroup consistently had poorer VA scores and took longer to complete the course. Further research must be completed with a larger sample size to fully understand the glare aversion strategies one must elicit when dealing with a contra lit glare source within the built environment, and to confirm the three glare strategies proposed by this pilot study.

Introduction Nearly all flat panel video display monitors have luminance and colour variations as the angle of view varies from the monitor’s perpendicular. The new MicrotileTM displays developed by Christie Digital are no exception to this general finding. A review of any book on colour science will show that there is substantial amount of literature on just noticeable colour differences within various colour spaces. Despite the wealth of data on the topic, there is no general consensus across different industries as to which colour space and colour difference equations are appropriate. Several factors like the background colour, object size, texture of the stimulus are different for different studies; these factors make it very difficult to determine precisely the effect of viewing angle on the perception of coloured images on the Microtiles display based on previous research. Hence, the objective of this thesis was to quantify the measured colour shifts of a Microtile display at different viewing angles, in steps of perceptible thresholds and to evaluate the acceptability of distortions at different viewing angles for complex scenes. Methods A preliminary experiment was setup to study the behaviour of Microtile display primaries as a function of viewing angle. The aim was to measure the shift in hue and luminance of the three primaries at different eccentricities (from 0o to 40o). The measured trend was used to simulate Microtile shifts on complex images for the rating task. In the first part of the perceptibility experiment, three reference colours were picked and 12 vectors heading towards the blue-yellow region of the L*a*b* colour space (pertaining to the colour shifts noticed with the Microtile displays). A uniform reference colour was presented in three of the four quadrants on the CRT monitor and one quadrant changed colour in the direction of the sampled vector. An adaptive, four alternate forced choice procedure was employed to determine thresholds for each of the 3 reference colours. The adaptive technique used was a ZEST paradigm. In the second part of the perceptibility experiment, eighteen directions were sampled around each reference colour. The rating task was based on simulating the measured attenuations of the Microtile primaries on complex scenes. Subjects rated the images both in terms of acceptability/unacceptability and as percentage image degradation. The simulation was presented on three static complex images, car, landscape and portrait. A total of 60 subjects participated in the study, 20 subjects for each experiment. All subjects were between the age group of 15 to 35 years of age and underwent battery of colour vision tests before being included in the study. All subjects included had average to superior colour discrimination as categorized using the FM-100 Hue discrimination test. Results Study1: The preliminary study on Microtile display characteristics as a function of viewing angle showed that all the three primaries decreased in luminance with change in viewing angle. The red primary decreased at a faster rate compared to the other two primaries. The trend presents as a decrease in luminance with the hue shifting towards the blue-green region of the CIE1974 L*a*b* space. Study 2: Results from both the first and second parts of the perceptibility experiment showed that the vectors sampled in different directions approximated to ellipsoids in the L*a*b* colour space. This finding was consistent with the colour discrimination literature. Vectors on the equi-luminance plane were significantly longer than the vectors on the non equi-Luminance plane. Results showed that the average perceptibility thresholds in the non equi-luminance direction were lower than 1∆ELab¬¬¬¬. Study 3: Results from the rating experiments showed that irrespective of the complexities in the images, distortions greater than five times thresholds were less than 50% acceptable and were rated to be at least 30% degraded. This corresponds to a viewing angle greater than 10o for a Microtile display. The relationship between the stimulus (ΔE) and subjective Image degradation judgements followed a linear relationship, with the portrait and landscape having similar functions, whereas the car was rated more degraded at lower ΔEs and less degraded at higher ΔEs compared with the other two scenes. Conclusion Perceptibility thresholds for different reference colours showed that the conventionally used calibration precision of 1 ΔELab is a lenient criterion. Perceptibility thresholds are at least 25% less for the Microtile display reference condition. From the results of the rating data a distortion greater than five times thresholds is less than 50% acceptable and appears to be at least 30% degraded for static complex images. However, the image quality judgments appear to be related to scene context, which requires further study.

Purpose: The prevalence of diabetes (DM) is increasing globally with type 2 diabetes (T2DM) being primarily responsible for this alarming trend. Age and DM have been associated with an increased prevalence of AR cataract in earlier studies but T2DM has not been considered separately from type 1 diabetes. Furthermore, study results have been inconsistent in terms of whether nuclear sclerosis (NS), cortical cataract (CC) or posterior subcapsular (PSC) are specifically associated with DM. The purpose of this thesis was to provide Canadian data on these issues while considering the limitations found in earlier studies in terms of variable age group selection and cataract definition. Logistic regression analysis was extended beyond risk analysis to model the prevalence of AR cataract across the human age range. Finally, as statins are commonly prescribed for patients with T2DM, the impact of using this pharmaceutical on AR cataract prevalence was investigated. Methods: A file review of over 6397 clinic files was performed to create the Waterloo Eye Study (WatES) database. Abstracted data included patient age and sex, the presence of early to late AR cataract (NS, CC, PSC or related lens extraction-LE), systemic health diagnoses including a diagnosis of T2DM or type 1 diabetes, and any medication used. Data quality was looked at through repeatability with double-entry of files and calculation of missing data rates. Comparisons were done between the study population demographics (age and sex) and those available on the general population and representative Canadian optometric patients. Prevalence of AR cataract was determined for the entire study group and for yearly age-groups. The probability of AR cataract generated from logistic regression analysis was used to model the prevalence of AR cataract over the entire age range of patients. Similar functions were determined for T2DM and non-diabetic (ND) subgroups and then again after further subdividing them into patients who did and did not use statins. The age of 50% prevalence of AR cataract were determined for each of these functions. Distribution rates of mixed and uniform cataract were calculated and compared for the T2DM and ND subgroups. Age of first lens extraction and differences in LE rates were also determined for these groups. Multivariable logistic regression analysis was done to determine odds ratios (OR) for associations between variables (patient age, being female, having a diagnosis of T2DM, smoking, systemic hypertension, and statin use) and the outcome of AR cataracts or its subtypes. Results: Data abstraction repeatability was found to be high and missing data rates were found to be low. While significant differences existed between the demographics of the general population and this clinic population, the sex and age distributions were comparable to optometric practices in Canada. The overall prevalence of AR cataract, NS, CC,and PSC in this population was 35.3%, 28.8%, 9.9%, and 3.6% respectively. The yearly prevalence of AR cataract in this population was found to increase in a sigmoid trend over the course of the human age span that began to rise after 38 years of age and approached 100% by 75 years of age. When modelled into a probability of cataract function, 50% prevalence of AR cataract occurred at 56.6 years of age. T2DM was reported in 452 WatES patients; 97% of whom were over 38 years of age. The probability of 50% AR cataract, NS, and CC prevalence occurred almost four years earlier in the T2DM subgroup compared to those without diabetes. PSC was much less prevalent and did not reach 50% levels, but the age of 10% prevalence was eight year earlier in the T2DM group compared to the ND group. Patients with T2DM had more mixed cataract, a higher rate of LE and an earlier age of first LE than non-diabetics. Statin use was reported in 761 patients; 96% who were over 38 years of age. Statin use was 3.5 times more common in patients with T2DM compared to non-diabetics. When the diabetic subgroups were further subdivided by those who do and do not use statins, the age of 50% probability of AR cataracts was now almost eight years earlier in the T2DM patients using statins compared to the ND patients who did not. The probability functions were similar between T2DM patients not using statins and ND patients who did report statin use. Having a diagnosis of T2DM was significantly associated with early to late NS and CC when controlling for statin use, whereas statin use was significantly associated with NS and PSC when controlling for a diagnosis of T2DM. Conclusions: AR cataract, T2DM and statin use were prevalent conditions in this clinic population, especially over 38 years of age. Modelling the prevalence of AR cataract over a broad age range could assist predicting cataract in Canadian optometric patients. A diagnosis of T2DM resulted in an earlier development of all three cataract subtypes, resulting in increased rates of LE and mixed cataract. However, the association was only significant for NS and CC when controlling for statin use. Given the frequent use of statins in patients with T2DM, the significant association found between statin use and increased risk of AR cataract warrants further study.

Purpose To examine soft contact lens fitting characteristics using anterior segment imaging techniques and comfort. The specific aims of each chapter are as follows: Chapter 2: To calibrate the new ZEISS VisanteTM anterior segment optical coherence tomographer (OCT) using references with known physical thickness and refractive index equal to the human cornea and to compare the Visante measures to those from a previous generation OCT (Zeiss-Humphrey OCT II). Chapter 3: The first purpose of this study was to measure the repeatability of the Visante TM OCT in a normal sample. The second was to compare corneal thickness measured with the Visante TM OCT to the Zeiss-Humphrey OCT II (model II, Carl Zeiss Meditec, Jena Germany) adapted for anterior segment imaging and to the Orbscan II TM (Bausch and Lomb, Rochester New York). Chapter 4: Conjunctival displacement observed with the edges of the contact lens, when imaged may be real or may be an artefact of all OCT imagers. A continuous surface appears displaced when the refractive index of the leading medium changes at the edge of a contact lens. To examine this effect, edges of the contact lenses were imaged on a continuous surface using the UHR-OCT. Contact lens edges on the human conjunctival tissue were also imaged to see if the lens indentation on the conjunctival tissue is real or an artefact at the edge of the lens. Chapter 5: The main purpose of this study was to determine if we can predict end of the day discomfort and dryness using clinical predictive variables. The second purpose of the study was to determine if there was any relationship between lens fitting characteristics and clinical complications and especially to the superior cornea and conjunctiva with a dispensing clinical trial. Methods Chapter 2: Twenty two semi-rigid lenses of specified thicknesses were manufactured using a material with refractive index of 1.376. Central thickness of these lenses was measured using VisanteTM OCT and Zeiss-Humphrey OCT II (Zeiss, Germany). Two data sets consisting of nominal measures (with a standard pachymeter of the lenses and one obtained using a digital micrometer) were used as references. Regression equations between the physical and optical (OCT) measures were derived to calibrate the devices. Chapter 3: Fifteen healthy participants were recruited. At the Day 1 visit the epithelial and total corneal thickness, across the central 10mm of the horizontal meridian were measured using the OCT II and the Visante TM OCT. Only total corneal thickness across the central 10mm of the horizontal meridian was measured using the Orbscan II. The order of these measurements was randomized. These measurements were repeated on Day 2. Each individual measurement was repeated three times and averaged to give a single result. Chapter 4: (2-D) Images of the edges of marketed silicone hydrogel and hydrogel lenses with refractive indices (n) ranging from 1.41-1.51 were taken placing them concave side down on a continuous surface. Five images for each lens were taken using a UHR-OCT system, operating at 1060 nm with ~3.2um (axial) and 10μm (lateral) resolution at the rate of 75,000 A-scans/s. The displacement of the glass slide beneath the lens edge was measured using Image J. Chapter 5: Thirty participants (neophytes) were included in the study and the four lenses (Acuvue Advance 8.3, Acuvue Advance 8.7, Pure Vision 8.3, and Pure Vision 8.6) were randomly assigned for each eye. The lenses were worn for a period of two weeks on a daily wear basis for 8 to 10hrs per day. Lens performance was monitored over the 2week period. Assessment of subjective comfort was made using visual analogue scales. Total corneal and epithelium thickness was measured using the Visante OCT, the lens edge profiles of the contact lenses were observed using the ultra-high resolution OCT and the conjunctival epithelial thinning was measured using the RTVue OCT. Conjunctival blood velocity was measured at the baseline and 2 week visit using a high magnification camera. Results Chapter 2: Before calibration, repeated measures ANOVA showed that there were significant differences between the mean lens thicknesses from each of the measurement methods (p<0.05), where Visante measurements were significantly different from the other three (OCT II, MG and OP) methods (p<0.05). Visante thickness was significantly higher than the microgauge measures (453±37.6 µm compared to 445.1±38.2 µm) and the OCT II was significantly lower (424.5±36.1 µm both, p<0.05). After calibration using the regression equations between the physical and optical measurements, there were no differences between OCT II and Visante OCT (p<0.05). Chapter 3: Mean central corneal and epithelial thickness using the Visante™ OCT after calibration at the apex of the cornea was 536± 27 µm (range, 563-509 µm) and 55± 2.3 µm (range, 57.3-52.7 µm), respectively. The mean corneal and epithelial thickness using OCT II at the apex was 520±25µm and 56±4.9 µm, respectively. The mean of total corneal thickness measured with the Orbscan II was 609±29µm. Visante OCT was the most repeatable for test-retest at the apex, nasal and temporal quadrants of the cornea compared to OCT II and Orbscan II. COR’s of Visante OCT ranged from ±7.71µm to ±8.98µm for total corneal thickness and ± 8.72 µm to ± 9.92 µm for epithelial thickness. CCC’s with Visante OCT were high for total corneal thickness for test-retest differences ranging from 0.97 to 0.99, CCC’s for epithelial thickness showed moderate concordance for both the instruments. Chapter 4: Results showed that artefactual displacement of the contact lens edge was observed when the lenses were imaged on the glass reference sphere, custom made rigid contact lenses (1.376) and on the conjunctival tissue. The displacement measured on the conjunctival tissue ranged from 7.0±0.86 µm for the Air Optix Night and Day to 17.4±0.22 µm for the Acuvue Advance contact lenses. The range of displacement with the soft lens edges imaged on the rigid contact lens was from 5.51±0.03 µm to 9.72±0.12 µm. Chapter 5: The lenses with the steepest sag (Acuvue Advance 8.3, Pure Vision 8.3) resulted not only with the tightest fit, but with compromise to the superior conjunctiva. This was especially seen with the Acuvue Advance lenses. The steeper lenses caused more total corneal swelling, superior epithelial thinning, mechanical compression of conjunctiva, conjunctival staining, bulbar hyperemia, conjunctival indentation and reduced blood flow at the lens edge. Not many associations were observed between baseline clinical and 2 weeks sensory variables. However, significant associations were observed when comparing the baseline clinical variables to end of the day sensory variables. Baseline clinical variables compared to 2 week clinical variables also showed significant correlations. Conclusions Chapter 2: Using reference lenses with refractive index of the cornea (1.376) allows rapid and simple calibration and cross calibration of instruments for measuring the corneal thickness. The Visante and OCT II do not produce measurements that are equal to physical references with refractive index equal to the human cornea. Chapter 3: There is good repeatability of corneal and epithelial thickness using each OCT for test-retest differences compared to the between instruments repeatability. Measurements of epithelial thickness are less repeatable compared to the total corneal thickness for the instruments used in the study. Chapter 4: When contact lenses are imaged in-situ using UHR-OCT the conjunctival tissue appeared displaced. This experiment indicates that this displacement is an artefact of all OCT imagers since a continuous surface (glass slide) was optically displaced indicating that the displacement that is observed is a function of the refractive index change and also the thickness of the contact lens edges. Chapter 5: Discomfort is a complex issue to resolve since it appears to be related to ocular factors such as the corneal and conjunctival topography and sagittal depth; to lens factors that is 1) how the sag depth of the lenses relate to the corneal/conjunctival shape and depth and therefore how well it moves on the eye. 2) Also with the lens material; whether they are high or low modulus, low or high water content, dehydration properties, wetting agents used and its resistance to deposits, lens edge profile and thickness and its interaction with the upper eyelid.

Purpose To study the impact of lactoferrin and lipids on the kinetic deposition and denaturation of lysozyme on contact lens materials. Methods The contact lenses investigated in this thesis included two silicone hydrogel lenses [AIR OPTIX AQUA; lotrafilcon B and ACUVUE OASYS; senofilcon A] and two conventional hydrogel lenses [ACUVUE 2; etafilcon A and PROCLEAR; omafilcon A]. All lenses were incubated in four solutions: a complex artificial tear solution (ATS); an ATS without lactoferrin; an ATS without lipids; and an ATS without lactoferrin and lipids. Following various time points, all lenses were prepared for lysozyme analysis using the methods below: • To quantify the kinetic uptake of lysozyme to different contact lens materials, I125-radiolabelled lysozyme was added to each incubation solution. Total lysozyme deposition was quantified using a gamma counter. • To study the activity of lysozyme deposited to contact lenses, a fluorescence-based lysozyme activity assay was compared to a turbidity assay. Potential interactions with lens materials and extraction solvents were evaluated. • To investigate the kinetic denaturation of lysozyme deposited to different contact lens materials, the fluorescence-based activity assay and the enzyme-linked immunosorbent assay were used. Results The presence of lactoferrin and lipids decreased lysozyme uptake to lotrafilcon B. Lysozyme deposition on senofilcon A was greater in the absence of lipids after day 21, however the opposite was seen with etafilcon A, where lysozyme uptake was lower without lipids in the ATS. Lactoferrin and/or lipids had no effect on lysozyme adsorption to omafilcon A. The fluorescence-based lysozyme activity assay demonstrated high sensitivity and a wide linear range of detection, which covers the amount of lysozyme typically extracted from contact lenses. Using this assay, lysozyme activity on both silicone hydrogel materials was lower in the presence of lipids in the ATS. In addition, lactoferrin had a protective effect on lysozyme activity for lysozyme sorbed to senofilcon A. Moreover, the presence of lactoferrin and/or lipids did not exhibit any effect on lysozyme denaturation with conventional hydrogel lenses. Conclusions The presence of lactoferrin and lipids in an artificial tear solution impacted lysozyme deposition and denaturation of lysozyme on various contact lenses. It is important for in vitro studies, when developing tear film models, to consider the effects of tear film components when investigating protein deposition and denaturation on contact lenses.