Purpose: To locate protein sorption on the surface and inside the matrix of soft contact lens materials and intraocular lenses (IOL). Methods: The proteins albumin and lysozyme were investigated as they are highly abundant in blood serum and tears, respectively. Proteins were conjugated with organic fluorescent probes and using confocal laser scanning microscopy (CLSM) the sorption profile to contact lenses and IOL could be determined. Radiolabeled protein was used for quantification purposes. • Albumin sorption to etafilcon A and lotrafilcon B was determined (Chapter 3) • Different fluorescent probes were used for conjugation and the impact on albumin sorption behaviour was investigated (Chapter 4) • Lysozyme sorption to nine different pHEMA-based and silicone hydrogel contact lenses was determined using two fluorescent probes (Chapter 5) • The efficiency of protein removal from contact lenses using contact lens care regimens was investigated (Chapter 6) • Albumin sorption to IOL materials was quantified and imaged using a modified CLSM technique (Chapter 7) Results: Albumin and lysozyme sorption profiles differed between materials, and were influenced by the fluorescent probes used for conjugation. After one day of incubation, both proteins could be located within all contact lens materials, except for lotrafilcon A and lotrafilcon B, which primarily allowed deposition on the lens surface. An increase in protein accumulation was found for most materials over the maximum investigated period of 14 days, using CLSM and radiolabel techniques. The efficiency of contact lens care regimens to remove lysozyme and albumin depended on the lens material, care regimen and protein type investigated. PMMA and silicone IOLs showed protein exclusively on the surface, while a hydrophilic acrylic IOL allowed penetration into the lens matrix over time. Despite the albumin penetration depth into hydrophilic acrylic, the highest albumin levels were determined for the silicone IOL. Conclusions: CLSM provides detailed information that can describe the protein distribution in transparent biomaterials, with scanning depths up to a few hundred microns. However, the CLSM data are primarily of qualitative value, which necessitates a quantitative technique (e.g. radiolabeling) to determine the total protein content.

The use of grading scales is common in clinical practice and research settings. A number of grading scales are available to the practitioner, however, despite their frequent use, they are only poorly understood and may be criticised for a number of things such as the variability of the assessments or the inequality of scale steps within or between scales. Hence, the global aim of this thesis was to study the McMonnies/Chapman-Davies (MC-D), Institute for Eye Research (IER), Efron, and validated bulbar redness (VBR) grading scales in order to (1) get a better understanding and (2) attempt a cross-calibration of the scales. After verifying the accuracy and precision of the objective and subjective techniques to be used (chapter 3), a series of experiments was conducted. The specific aims of this thesis were as follows: • Chapter 4: To use physical attributes of redness to determine the accuracy of the four bulbar redness grading scales. • Chapter 5: To use psychophysical scaling to estimate the perceived redness of the four bulbar redness grading scales. • Chapter 6: To investigate the effect of using reference anchors when scaling the grading scale images, and to convert grades between scales. • Chapter 7: To grade bulbar redness using cross-calibrated versions of the MC-D, IER, Efron, and VBR grading scales. Methods: • Chapter 4: Two image processing metrics, fractal dimension (D) and % pixel coverage (% PC), as well as photometric chromaticity (u’) were selected as physical measures to describe and compare redness in the four bulbar redness grading scales. Pearson correlation coefficients were calculated between each set of image metrics and the reference image grades to determine the accuracy of the scales. • Chapter 5: Ten naïve observers were asked to arrange printed copies of modified versions of the reference images (showing vascular detail only) across a distance of 1.5m for which only start and end point were indicated by 0 and 100, respectively (non-anchored scaling). After completion of scaling, the position of each image was hypothesised to reflect its perceived bulbar redness. The averaged perceived redness (across observers) for each image was used for comparison to the physical attributes of redness as determined in chapter 4. • Chapter 6: The experimental setup from chapter 5 was modified by providing the reference images of the VBR scale as additional, unlabelled anchors for psychophysical scaling (anchored scaling). Averaged perceived redness from anchored scaling was compared to non-anchored scaling, and perceived redness from anchored scaling was used to cross-calibrate grades between scales. • Chapter 7: The modified reference images of each grading scale were positioned within the 0 to 100 range according to their averaged perceived redness from anchored scaling, one scale at a time. The same 10 observers who had participated in the scaling experiments were asked to represent perceived bulbar redness of 16 sample images by placing them, one at a time, relative to the reference images of each scale. Perceived redness was taken as the measured position of the placed image from 0 and was averaged across observers. Results: • Chapter 4: Correlations were high between reference image grades and all sets of objective metrics (all Pearson’s r’s≥0.88, p≤0.05); each physical attribute pointed to a different scale as being most accurate. Independent of the physical attribute used, there were wide discrepancies between scale grades, with sometimes little overlap of equivalent levels when comparing the scales. • Chapter 5: The perceived redness of the reference images within each scale was ordered as expected, but not all consecutive within-scale levels were rated as having different redness. Perceived redness of the reference images varied between scales, with different ranges of severity being covered by the images. The perceived redness was strongly associated with the physical attributes of the reference images. • Chapter 6: There were differences in perceived redness range and when comparing reference levels between scales. Anchored scaling resulted in an apparent shift to lower perceived redness for all but one reference image compared to non-anchored scaling, with the rank order of the 20 images for both procedures remaining fairly constant (Spearman’s ρ=0.99). • Chapter 7: Overall, perceived redness depended on the sample image and the reference scale used (RM ANOVA; p=0.0008); 6 of the 16 images had a perceived redness that was significantly different between at least two of the scales. Between-scale correlation coefficients of concordance (CCC) ranged from 0.93 (IER vs. Efron) to 0.98 (VBR vs. Efron). Between-scale coefficients of repeatability (COR) ranged from 5 units (IER vs. VBR) to 8 units (IER vs. Efron) for the 0 to 100 range. Conclusions: • Chapter 4: Despite the generally strong linear associations between the physical characteristics of reference images in each scale, the scales themselves are not inherently accurate and are too different to allow for cross-calibration based on physical redness attributes. • Chapter 5: Subjective estimates of redness are based on a combination of chromaticity and vessel-based components. Psychophysical scaling of perceived redness lends itself to being used to cross calibrate the four clinical scales. • Chapter 6: The re-scaling of the reference images with anchored scaling suggests that redness was assessed based on within-scale characteristics and not using absolute redness scores, a mechanism that may be referred to as clinical scale constancy. The perceived redness data allow practitioners to modify the grades of the scale they commonly use so that comparisons of grading estimates between calibrated scales may be made. • Chapter 7: The use of the newly calibrated reference grades showed close agreement between grading estimates of all scales. The between-scale variability was similar to the variability typically observed when a single scale is repeatedly used. Perceived redness appears to be dependent upon the dynamic range of the reference images of the scale. In conclusion, this research showed that there are physical and perceptual differences between the reference images of all scales. A cross-calibration of the scales based on the perceived redness of the reference images provides practitioners with an opportunity to compare grades across scales, which is of particular value in research settings or if the same patient is seen by multiple practitioners who are familiar with using different scales.

In Canada, as baby boomers age, there will be an increase in the percentage of seniors within the general population (Statistics Canada, 2006). Seniors often have difficulty in performing certain everyday tasks and have greater risk of having health issues. As such, it becomes increasingly important to understand factors that pose difficulty for this group of people. As people get older, many visual functions such as visual acuity, contrast sensitivity, and glare are known to deteriorate (Haegerstrom-Portnoy, 2005). However, when considering activities that aid mobility such as driving and walking, vision related variables are not the only ones that create difficulty for older individuals. A sensory variable such as attention, in conjunction with vision, has been shown in previous studies to be a good predictor of difficulties encountered by the elderly (McGwin, Owsley, & Ball, 1998; Owsley, McGwin, Sloane, Stalvey, & Wells, 2001). Moreover, inattention and distraction seem to be common causes of automobile accidents as well as falls. The work load imposed on the working memory can impact distractibility and inattention. In mobility related activities such as driving and walking, individuals perceive objects that are increasing in size. Experiments were designed to investigate the factors that affect the perception of targets that are enlarging in size. Size matching of expanding targets to a previously presented static target, was investigated in a group of younger participants with normal vision using central or peripheral vision. The results show that size estimates differ depending on whether the target appears in the central visual field or in the periphery. The participants respond faster to targets that appear in the periphery compared to those in the centre/midline. In the subsequent set of experiments we compared the performance of younger and older participants using a dual task paradigm where individuals had to perform two tasks concurrently, one of which was to match the size of an enlarging target. Attention was modulated in the dual tasks by varying the difficulty of the secondary task. It has been found that older individuals have difficulty processing multiple visual tasks or performing multiple tasks in general (Pashler, 1994a, 1994b, 1998; Verhaeghen et al., 2003). Compared to younger individuals, older individuals were found to have greater performance difficulty in the highly demanding dual tasks. These results are compared to those observed in studies of psychological refractory period effects. The differences between the young and older individuals are discussed with respect to limited capacity and bottle neck models of attention. Furthermore, eye movement measures in the dual tasks seem to provide evidence of difficulty in task switching for the older observers. The thesis also investigated the functional field of view of younger and older individuals. By assessing the functional field of view (FFOV) using a method employed earlier by Coeckelbergh et al., (2004a), significant overall age related differences were found. Multiple characteristics of what might affect the FFOV as measured by the attended field of view (AFOV) were also investigated (e.g., impact of a pop out distracter and divided attention). It was found that differences between the two age groups occurred in all conditions. The presence of irrelevant distracters had a greater impact on the older individuals compared to the younger group, whereas divided attention or the presence of the pop out distracter did not affect either age group. Attention processing seemed to be similar for both the younger and older individuals and, therefore, the differences between the age groups appear to be at a quantitative level rather than a qualitative level.

Introduction and Purpose: Vascular pathologies play an important role in the etiology and progression of number of ocular diseases. Many instruments are developed to monitor retinal hemodynamics, including the Canon Laser Blood Flowmeter (CLBF), in an attempt to better understand the pathophysiology of the disease (Chapter 2). The purpose of this thesis is to determine the impact of light scatter on retinal arteriolar hemodynamic measurement assessed by the CLBF as intraocular light scatter is an inevitable consequence of ageing and particularly cataract. Methodology: Chapter 4 – Artificial light scatter model: One eye from each of 10 healthy young subjects between the ages of 18 and 30 (23.6 ± 3.4) was randomly selected. To simulate light scatter, cells comprising a plastic collar and two plano lenses were filled with solutions of differing concentrations of polystyrene microspheres (Polysciences Inc., USA). 0.002%, 0.004%, 0.006%, 0.008% were prepared, as well as distilled water only. After a preliminary screening to confirm subject eligibility, seven arteriolar hemodynamic measurements were taken by randomly placing the cells between the CLBF objective lens and the subjects’ cornea. Chapter 5 – Ten patients scheduled for extracapsular cataract extraction using phacoemulsification and intraocular lens implantation between the ages of 61 and 84 (mean age 73 years, SD ± 8) were prospectively recruited. Two visits were required to complete the study; One prior to the surgery and one at least six weeks after the surgery to allow for full post-operative recovery. The severity of cataract was documented using the Lens Opacity Classification System (LOCS, III) at the first visit. Each subject underwent visual function assessment at both visits using logMAR Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity charts and the Brightness Acuity Tester (BAT). Retinal arteriolar hemodynamics were measured at both visits using the high intensity setting of the Canon Laser Blood Flowmeter. Results: Chapter 4: Our light scatter model resulted in an artifactual increase of retinal arteriolar diameter (p<0.0001) and thereby increased retinal blood flow (p<0.0001). The 0.006% and 0.008% microsphere concentrations produced significantly higher diameter and flow values than baseline. Centerline blood velocity, however, was not affected by light scatter. Retinal arteriolar diameter values were significantly less with the high intensity laser than with the low intensity laser (p=0.0007). Chapter 5: Group mean retinal arteriolar diameter and blood flow were reduced following extracapsular cataract extraction (Wilcoxon signed-rank test, p=0.022 and p=0.028 respectively); however, centerline blood velocity was unchanged (Wilcoxon signed-rank test, p=0.074). Conclusions: Using an artificial light scatter model (Chapter 3), we demonstrated that the densitometry assessment of vessel diameter is increasingly impacted as the magnitude of artificial light scatter increases; this effect can be partially negated by increasing laser intensity. We showed similar results in the presence of cataract (Chapter 4) by measuring the retinal arteriolar hemodynamics before and after removal of cataract. Care needs to be exercised in the interpretation of studies of retinal vessel diameter that use similar densitometry techniques as cataract is an inevitable consequence of aging.

A previous study in chickens revealed that myosin light chain kinase (MLCK), f actin, and myosin are found on the crystalline lens. Their polygonal arrangement at the posterior surface resembles a muscle tissue, which suggests that these proteins may have a contractile role in accommodation. The ciliary muscle in chickens is skeletal in nature and, therefore, chickens were used to test the hypothesis that contractile microfilaments play a role in accommodation. Ciliary nerve-induced accommodation was measured in the presence of an MLCK inhibitor 1-(5-Iodonaphthalene-1-sulfonyl)-1H-hexahydro-1,4-diazepine hydrochloride (ML-7). Eyes of 6-day old white Leghorn chickens (gallus gallus domesticus) were enucleated in Tyrode’s saline solution while keeping the ciliary nerve intact. One eye was treated with ML-7 and the other eye was treated with vehicle only. Three concentrations of ML-7 were used: 1 µM, 10 µM, and 100 µM. Two experiments were carried out, one including a (3×10 min) wash and one without. Focal lengths of the vehicle- and ML-7-treated eyes were measured before, during and after accommodation. Immunoblots were used to detect the amount of phosphorylated myosin with and without the inhibitor. Focal lengths for accommodation were shorter than those at rest (p<0.001). In the wash experiment, vehicle-treated eyes had higher accommodative amplitudes compared to ML-7-treated eyes for all three dosage groups. In the no-wash experiment, only the 1 µM group demonstrated the same trend as the wash experiment. For the 10 µM and 100 µM groups, ML-7-treated eyes had higher accommodative amplitudes compared to vehicle-treated eyes. Immunoblots revealed varying amounts of inhibition within pairs of eyes as well as between birds for both experiments. Results from this experiment indicate that ML-7 was not effective at determining whether contractile microfilaments found on the lens contribute to accommodation.

Purpose: To locate protein sorption on the surface and inside the matrix of soft contact lens materials and intraocular lenses (IOL). Methods: The proteins albumin and lysozyme were investigated as they are highly abundant in blood serum and tears, respectively. Proteins were conjugated with organic fluorescent probes and using confocal laser scanning microscopy (CLSM) the sorption profile to contact lenses and IOL could be determined. Radiolabeled protein was used for quantification purposes. • Albumin sorption to etafilcon A and lotrafilcon B was determined (Chapter 3) • Different fluorescent probes were used for conjugation and the impact on albumin sorption behaviour was investigated (Chapter 4) • Lysozyme sorption to nine different pHEMA-based and silicone hydrogel contact lenses was determined using two fluorescent probes (Chapter 5) • The efficiency of protein removal from contact lenses using contact lens care regimens was investigated (Chapter 6) • Albumin sorption to IOL materials was quantified and imaged using a modified CLSM technique (Chapter 7) Results: Albumin and lysozyme sorption profiles differed between materials, and were influenced by the fluorescent probes used for conjugation. After one day of incubation, both proteins could be located within all contact lens materials, except for lotrafilcon A and lotrafilcon B, which primarily allowed deposition on the lens surface. An increase in protein accumulation was found for most materials over the maximum investigated period of 14 days, using CLSM and radiolabel techniques. The efficiency of contact lens care regimens to remove lysozyme and albumin depended on the lens material, care regimen and protein type investigated. PMMA and silicone IOLs showed protein exclusively on the surface, while a hydrophilic acrylic IOL allowed penetration into the lens matrix over time. Despite the albumin penetration depth into hydrophilic acrylic, the highest albumin levels were determined for the silicone IOL. Conclusions: CLSM provides detailed information that can describe the protein distribution in transparent biomaterials, with scanning depths up to a few hundred microns. However, the CLSM data are primarily of qualitative value, which necessitates a quantitative technique (e.g. radiolabeling) to determine the total protein content.

The use of grading scales is common in clinical practice and research settings. A number of grading scales are available to the practitioner, however, despite their frequent use, they are only poorly understood and may be criticised for a number of things such as the variability of the assessments or the inequality of scale steps within or between scales. Hence, the global aim of this thesis was to study the McMonnies/Chapman-Davies (MC-D), Institute for Eye Research (IER), Efron, and validated bulbar redness (VBR) grading scales in order to (1) get a better understanding and (2) attempt a cross-calibration of the scales. After verifying the accuracy and precision of the objective and subjective techniques to be used (chapter 3), a series of experiments was conducted. The specific aims of this thesis were as follows: • Chapter 4: To use physical attributes of redness to determine the accuracy of the four bulbar redness grading scales. • Chapter 5: To use psychophysical scaling to estimate the perceived redness of the four bulbar redness grading scales. • Chapter 6: To investigate the effect of using reference anchors when scaling the grading scale images, and to convert grades between scales. • Chapter 7: To grade bulbar redness using cross-calibrated versions of the MC-D, IER, Efron, and VBR grading scales. Methods: • Chapter 4: Two image processing metrics, fractal dimension (D) and % pixel coverage (% PC), as well as photometric chromaticity (u’) were selected as physical measures to describe and compare redness in the four bulbar redness grading scales. Pearson correlation coefficients were calculated between each set of image metrics and the reference image grades to determine the accuracy of the scales. • Chapter 5: Ten naïve observers were asked to arrange printed copies of modified versions of the reference images (showing vascular detail only) across a distance of 1.5m for which only start and end point were indicated by 0 and 100, respectively (non-anchored scaling). After completion of scaling, the position of each image was hypothesised to reflect its perceived bulbar redness. The averaged perceived redness (across observers) for each image was used for comparison to the physical attributes of redness as determined in chapter 4. • Chapter 6: The experimental setup from chapter 5 was modified by providing the reference images of the VBR scale as additional, unlabelled anchors for psychophysical scaling (anchored scaling). Averaged perceived redness from anchored scaling was compared to non-anchored scaling, and perceived redness from anchored scaling was used to cross-calibrate grades between scales. • Chapter 7: The modified reference images of each grading scale were positioned within the 0 to 100 range according to their averaged perceived redness from anchored scaling, one scale at a time. The same 10 observers who had participated in the scaling experiments were asked to represent perceived bulbar redness of 16 sample images by placing them, one at a time, relative to the reference images of each scale. Perceived redness was taken as the measured position of the placed image from 0 and was averaged across observers. Results: • Chapter 4: Correlations were high between reference image grades and all sets of objective metrics (all Pearson’s r’s≥0.88, p≤0.05); each physical attribute pointed to a different scale as being most accurate. Independent of the physical attribute used, there were wide discrepancies between scale grades, with sometimes little overlap of equivalent levels when comparing the scales. • Chapter 5: The perceived redness of the reference images within each scale was ordered as expected, but not all consecutive within-scale levels were rated as having different redness. Perceived redness of the reference images varied between scales, with different ranges of severity being covered by the images. The perceived redness was strongly associated with the physical attributes of the reference images. • Chapter 6: There were differences in perceived redness range and when comparing reference levels between scales. Anchored scaling resulted in an apparent shift to lower perceived redness for all but one reference image compared to non-anchored scaling, with the rank order of the 20 images for both procedures remaining fairly constant (Spearman’s ρ=0.99). • Chapter 7: Overall, perceived redness depended on the sample image and the reference scale used (RM ANOVA; p=0.0008); 6 of the 16 images had a perceived redness that was significantly different between at least two of the scales. Between-scale correlation coefficients of concordance (CCC) ranged from 0.93 (IER vs. Efron) to 0.98 (VBR vs. Efron). Between-scale coefficients of repeatability (COR) ranged from 5 units (IER vs. VBR) to 8 units (IER vs. Efron) for the 0 to 100 range. Conclusions: • Chapter 4: Despite the generally strong linear associations between the physical characteristics of reference images in each scale, the scales themselves are not inherently accurate and are too different to allow for cross-calibration based on physical redness attributes. • Chapter 5: Subjective estimates of redness are based on a combination of chromaticity and vessel-based components. Psychophysical scaling of perceived redness lends itself to being used to cross calibrate the four clinical scales. • Chapter 6: The re-scaling of the reference images with anchored scaling suggests that redness was assessed based on within-scale characteristics and not using absolute redness scores, a mechanism that may be referred to as clinical scale constancy. The perceived redness data allow practitioners to modify the grades of the scale they commonly use so that comparisons of grading estimates between calibrated scales may be made. • Chapter 7: The use of the newly calibrated reference grades showed close agreement between grading estimates of all scales. The between-scale variability was similar to the variability typically observed when a single scale is repeatedly used. Perceived redness appears to be dependent upon the dynamic range of the reference images of the scale. In conclusion, this research showed that there are physical and perceptual differences between the reference images of all scales. A cross-calibration of the scales based on the perceived redness of the reference images provides practitioners with an opportunity to compare grades across scales, which is of particular value in research settings or if the same patient is seen by multiple practitioners who are familiar with using different scales.

In Canada, as baby boomers age, there will be an increase in the percentage of seniors within the general population (Statistics Canada, 2006). Seniors often have difficulty in performing certain everyday tasks and have greater risk of having health issues. As such, it becomes increasingly important to understand factors that pose difficulty for this group of people. As people get older, many visual functions such as visual acuity, contrast sensitivity, and glare are known to deteriorate (Haegerstrom-Portnoy, 2005). However, when considering activities that aid mobility such as driving and walking, vision related variables are not the only ones that create difficulty for older individuals. A sensory variable such as attention, in conjunction with vision, has been shown in previous studies to be a good predictor of difficulties encountered by the elderly (McGwin, Owsley, & Ball, 1998; Owsley, McGwin, Sloane, Stalvey, & Wells, 2001). Moreover, inattention and distraction seem to be common causes of automobile accidents as well as falls. The work load imposed on the working memory can impact distractibility and inattention. In mobility related activities such as driving and walking, individuals perceive objects that are increasing in size. Experiments were designed to investigate the factors that affect the perception of targets that are enlarging in size. Size matching of expanding targets to a previously presented static target, was investigated in a group of younger participants with normal vision using central or peripheral vision. The results show that size estimates differ depending on whether the target appears in the central visual field or in the periphery. The participants respond faster to targets that appear in the periphery compared to those in the centre/midline. In the subsequent set of experiments we compared the performance of younger and older participants using a dual task paradigm where individuals had to perform two tasks concurrently, one of which was to match the size of an enlarging target. Attention was modulated in the dual tasks by varying the difficulty of the secondary task. It has been found that older individuals have difficulty processing multiple visual tasks or performing multiple tasks in general (Pashler, 1994a, 1994b, 1998; Verhaeghen et al., 2003). Compared to younger individuals, older individuals were found to have greater performance difficulty in the highly demanding dual tasks. These results are compared to those observed in studies of psychological refractory period effects. The differences between the young and older individuals are discussed with respect to limited capacity and bottle neck models of attention. Furthermore, eye movement measures in the dual tasks seem to provide evidence of difficulty in task switching for the older observers. The thesis also investigated the functional field of view of younger and older individuals. By assessing the functional field of view (FFOV) using a method employed earlier by Coeckelbergh et al., (2004a), significant overall age related differences were found. Multiple characteristics of what might affect the FFOV as measured by the attended field of view (AFOV) were also investigated (e.g., impact of a pop out distracter and divided attention). It was found that differences between the two age groups occurred in all conditions. The presence of irrelevant distracters had a greater impact on the older individuals compared to the younger group, whereas divided attention or the presence of the pop out distracter did not affect either age group. Attention processing seemed to be similar for both the younger and older individuals and, therefore, the differences between the age groups appear to be at a quantitative level rather than a qualitative level.

Introduction and Purpose: Vascular pathologies play an important role in the etiology and progression of number of ocular diseases. Many instruments are developed to monitor retinal hemodynamics, including the Canon Laser Blood Flowmeter (CLBF), in an attempt to better understand the pathophysiology of the disease (Chapter 2). The purpose of this thesis is to determine the impact of light scatter on retinal arteriolar hemodynamic measurement assessed by the CLBF as intraocular light scatter is an inevitable consequence of ageing and particularly cataract. Methodology: Chapter 4 – Artificial light scatter model: One eye from each of 10 healthy young subjects between the ages of 18 and 30 (23.6 ± 3.4) was randomly selected. To simulate light scatter, cells comprising a plastic collar and two plano lenses were filled with solutions of differing concentrations of polystyrene microspheres (Polysciences Inc., USA). 0.002%, 0.004%, 0.006%, 0.008% were prepared, as well as distilled water only. After a preliminary screening to confirm subject eligibility, seven arteriolar hemodynamic measurements were taken by randomly placing the cells between the CLBF objective lens and the subjects’ cornea. Chapter 5 – Ten patients scheduled for extracapsular cataract extraction using phacoemulsification and intraocular lens implantation between the ages of 61 and 84 (mean age 73 years, SD ± 8) were prospectively recruited. Two visits were required to complete the study; One prior to the surgery and one at least six weeks after the surgery to allow for full post-operative recovery. The severity of cataract was documented using the Lens Opacity Classification System (LOCS, III) at the first visit. Each subject underwent visual function assessment at both visits using logMAR Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity charts and the Brightness Acuity Tester (BAT). Retinal arteriolar hemodynamics were measured at both visits using the high intensity setting of the Canon Laser Blood Flowmeter. Results: Chapter 4: Our light scatter model resulted in an artifactual increase of retinal arteriolar diameter (p<0.0001) and thereby increased retinal blood flow (p<0.0001). The 0.006% and 0.008% microsphere concentrations produced significantly higher diameter and flow values than baseline. Centerline blood velocity, however, was not affected by light scatter. Retinal arteriolar diameter values were significantly less with the high intensity laser than with the low intensity laser (p=0.0007). Chapter 5: Group mean retinal arteriolar diameter and blood flow were reduced following extracapsular cataract extraction (Wilcoxon signed-rank test, p=0.022 and p=0.028 respectively); however, centerline blood velocity was unchanged (Wilcoxon signed-rank test, p=0.074). Conclusions: Using an artificial light scatter model (Chapter 3), we demonstrated that the densitometry assessment of vessel diameter is increasingly impacted as the magnitude of artificial light scatter increases; this effect can be partially negated by increasing laser intensity. We showed similar results in the presence of cataract (Chapter 4) by measuring the retinal arteriolar hemodynamics before and after removal of cataract. Care needs to be exercised in the interpretation of studies of retinal vessel diameter that use similar densitometry techniques as cataract is an inevitable consequence of aging.

Down syndrome (DS) is the most common genetic cause of mental challenge in individuals and is associated with many ocular disorders. One of these anomalies which is frequently present in this population is reduced accommodation and many studies have reported this. Accommodation is the ability of the crystalline lens in the eye to focus for objects at different distances. Prescribing bifocals could potentially help in correcting the resultant inaccurate focus, although this modality of treatment is not very commonly practiced. The impact of bifocals on reading and literacy skills (academic skills) as well as visual-perceptual skills in individuals with DS has not been studied previously. The aim of this study was to investigate the impact of bifocals on the educational attainment of children and young adults with DS who have reduced accommodation and monitor their performance longitudinally. This is the first time that the impact of bifocal provision on the functional performance of children and young adults with DS has been studied. Also for the first time in children with DS, frequent measures of performance have been used to control for progression with time before and after bifocal prescription. A battery of tests comprising early literacy and visual-perceptual skills was administered before and after bifocal prescription. Accommodation and printing skills were also measured periodically. It was expected that the prescription of bifocals would help to improve near visual acuity and that the improved near acuity would result in educational achievements at school. Compliance with spectacle wear and school reports were also considered. A longitudinal observational study design was utilized with each child acting as his/her own control. Fourteen children and teenagers aged 8-18 with DS were recruited and underwent a basic optometric exam including measurement of their accommodative ability and a cycloplegic refraction. Seventy nine percent required a change in their spectacle prescription and were prescribed single vision (SV) lenses. One hundred percent had reduced accommodation both before and after new SV glasses were prescribed. Distance visual acuity did not significantly improve with SV lenses (p>0.05) but near visual acuity showed a significant improvement (p-=0.015) from 0.64±0.25 logMAR to 0.54±0.20 logMAR. A high prevalence of high refractive errors, including both hyperopia and myopia, was observed t andnear visual acuity even with a habitual correctionwas reduced compared to distance VA. A full battery of reading and visual-perceptual tests was administered with SV lenses. Thereafter the participants were followed for 6 months and monthly subtests (probes) of literacy skills and printing tasks were administered. These “probes” acted as immediate indicators of the child’s performance with his/her correction and change in performance over this time period was monitored. Over the 6 months the participants showed no noteworthy progression in their literacy skills. The group of participants performed at an age-equivalent between 3-10 years. The quality of printing formation in this population has been studied for the first time and showed no significant change over time. It was observed that some aspects of visual-perceptual and early literacy skills could be measured in all the participants. Chronological age and receptive vocabulary were significantly correlated with visual motor integration and Word Identification. Eighty five percent of the participants were prescribed bifocals with additions ranging from +1.00D to +3.50D at the 6th month after the provision of SV lenses. Post-bifocal measures of visual acuity, accommodation, visual-perceptual and early literacy skills were taken 1-2 weeks, and finally 5 months, after bifocal correction. Throughout the pre- and post-bifocal period, verbal compliance with spectacle wear was assessed through school and parental reports. The mean near logMAR VA improved with bifocals (p=0.007) compared to SV lenses. Accommodative accuracy improved with bifocals (less accommodative lag) compared to SV lenses (p=0.002) but there was no change in the accommodation exerted through the distance portion of the lens compared to SV lenses (p=0.423). There was a main effect of bifocals on sight words (p=0.013), Word Identification (p=0.047), and 2 out of 3 tests of visual perception (p<0.05). It was observed that bifocals have a positive impact on the children’s visual and school performance and this was supported by reports of improved performance in school for nine out of eleven individuals who were prescribed bifocals. The children adapted to bifocals more readily than the SV glasses, wearing them for the majority of their waking time. All the sessions of early literacy and visual-perceptual skills administered throughout the duration of the study were videotaped and were then analyzed by a naïve examiner. The time taken to perform each task was calculated and compared between the main single vision and bifocal visits. There was a significant decrease in the completion times on the test battery with bifocals for Word Identification (p=0.0015) and the Dolch sight words (p=0.048). All participants who completed the monthly probes took less time to complete the Dolch sight words (p= 0.025) and the number writing task (p=0.001) with bifocals. Similar results were not observed for the visual-perceptual tests. Performance in the monthly probes was compared before and after bifocal prescription in terms of the average raw scores and time taken. The rate of improvement in performance with bifocals was calculated by plotting the test scores against time and determing the regression lines. There was an overall significant improvement in the monthly probe scores of Word Identification (p=0.050), Dolch sight words (p=0.025) and the number test (p=0.023) with bifocals. The rate of progression in scores increased with bifocals for the Word Identification (p=0.008). Evidence of improved and faster performance with bifocals on some literacy skills was seen. It was concluded that bifocals, which result in improved near focusing, help individuals with DS to maximize their educational potential. It is suggested that more children and teenagers with DS will benefit from bifocal prescription, as they were observed to improve near visual acuity and enable better focusing for near. This thesis has provided a comprehensive analysis of the some tests of literacy, visual- perceptual and early printing skills before and after a bifocal prescription in a group of children and teenagers with Down syndrome. This is the first study to longitudinally monitor the educational impact of bifocals in a population with Down syndrome. Furthermore, the quality of printing formation in this population is a previously unstudied area and was studied longitudinally prior to and after bifocal intervention. The impact of bifocals on printing skills is also discussed. Another novel approach was that all the literacy, writing and visual-perceptual tasks sessions were videotaped to calculate the time taken to complete each task pre- and post-bifocals. This thesis is an addition to the existing literature on bifocal prescription in Down syndrome populations. From the findings in this thesis, the following recommendations are made in order to improve the standard of clinical eye care in this population. Measurement of accommodation should be considered a routine test in the clinical ocular examination for young individuals with DS, now that it is known that many of them present with accommodative deficits. When accommodation is found to be reduced, prescription of bifocals is indicated and should also become the standard of care in this population.