Contact lens success is primarily driven by comfort of the lens in eye. Over the years, many modifications have been made to the lens surface and bulk material to improve comfort of the lens, however 50% of contact lens wearers still report dry eye symptoms while wearing their lenses. Wettability of the lens material plays a large role in lens comfort, primarily due to its influence in tear film stability. In vitro wettability of contact lenses has typically been assessed by measuring the water contact angle on the lens surface. Currently there are three techniques to measure the in vitro wettability of contact lenses, the sessile drop technique, captive bubble technique, and the Wilhelmy balance method. To date, there is much published on assessing wettability using the sessile drop and captive bubble technique, however there is no data published looking at the in vitro wettability of hydrogel contact lenses measured by the Wilhelmy balance method. Accumulation and deposition of tear components on the lens surface can also affect lens performance, by altering the wettability of the lens surface and causing lens spoilage. The majority of in vitro studies looking at deposition of tear components on the lens surface dope the lenses in tear solutions for a set period of time. None of these studies have investigated the impact of exposing the lenses to tear solutions, then exposing them to the air and then back into the tear solution, which mimics the process during blinking. In Chapter 2, an evaluation of the influence of lens preparation on the wettability of contact lenses measured by the sessile drop technique was conducted. The wettability of 6 silicone hydrogel and one conventional lens material was assessed. Lenses were blot dried on either a microfiber cloth or lens paper for different drying periods and contact angles were measured using the sessile drop technique. There were large variations in results using the microfiber cloth after all drying periods, but there was little variation in results after lenses were blot dried on lens paper for approximately 20 seconds. Thus, it was determined that for future contact angle analysis using the sessile drop technique that lenses should be blot dried for roughly 20 seconds on lens paper. This method was used consistently for the rest of the experiments in which the sessile drop technique was used to measure contact angles. The remainder of Chapter 2 compared the contact angles of different lens materials measured by the sessile drop technique and Wilhelmy balance method. The wettability of five different silicone hydrogel lens materials was assessed directly out-of-blister and after a 48 hour soak in saline. There were significant differences in contact angles for the lens materials between the two techniques. There were also significant differences in contact angles directly out-of-blister and after the 48 hour soak. Results from this study suggested that different methods of measuring wettability can produce different results and that blister pack solutions can alter the wettability of lens materials. Chapter 3 measured the physical properties of blister pack solutions of silicone hydrogel lenses. The pH, osmolality, surface tension, and viscosity of the blister solutions for 9 silicone hydrogel lenses, 2 conventional lenses, and 2 saline solutions were measured. The osmolality of the blister solutions followed a trend, in that blister solutions manufactured by the same company had the same osmolality. Products produced by Johnson & Johnson had the highest osmolality. Blister solutions that contained additional wetting agents had higher viscosities compared to blister solutions without added wetting agents. The main conclusion from this study was that adding wetting agents to blister solutions could alter the physical properties of the blister solutions. The purpose of Chapter 4 was to measure the physical properties of the blister pack solutions of daily disposable lenses and to evaluate the wettability of the lens materials and substantivity of the blister solutions, using a method in which lenses were cycled through 5 minute soaks in saline to mimic blinking. Five daily disposable lens materials were evaluated, one of which was shipped in a blister solution with added surfactants and wetting agents. The wettability of the lenses was assessed using the sessile drop technique and Wilhelmy balance method. The lens with the modified blister solution had a lower surface tension and higher viscosity compared to all the other blister solutions. The same trend in osmolalties as those reported in Chapter 3, were found with blister solutions made by the same manufacturer having the same osmolality. The wettability varied across lens materials. Overall, the lens material with the added components to the blister solution had the lowest contact angle. Chapter 5 investigated the deposition of tear components onto the surface of conventional and silicone hydrogel lens materials and looked at the impact of this on changes in wettability. Three lens materials used in Chapter 4 were exposed to a saline solution, lysozyme solution, and a complex tear solution for 5 minutes, 1 hour, 4 hours, and 8 hours. The wettability was assessed after each time point using the sessile drop and Wilhelmy balance methods. There was little to no deposition on the lens materials that had the highest in vitro CAs in Chapter 4, exemplified by no change in wettability after being soaked in the lysozyme and complex tear solutions. There was deposition on the lens materials with the lowest CAs in Chapter 4, exemplified by a significant increase in wettability after being soaked in the lysozyme and complex tear solutions. Results indicate that there is some deposition onto one lens material, as shown by the change in wettability of the lens surface. These results were further used to validate a method used in Chapter 6. The experiment conducted in Chapter 6 was similar to the experiment in Chapter 5, except that the lenses were not soaked in the three solutions but rather exposed to the solutions in a “model blink cell”. The model blink cell moves lenses in and out of solution at a set time interval, in an attempt to mimic blinking. The interval was set so the lenses would be placed for 1 second in solution and 5 seconds exposed to the air. The same lens materials used in Chapter 5 were used in for this experiment. The lenses were exposed to a saline solution, lysozyme solution and complex tear solution for 5 minutes, 1 hour, 4 hours, and 8 hours. Much like in Chapter 5, deposition on the lens materials was determined by a change in the lens wettability. There were differences in the results of this chapter and that of Chapter 5, with deposition occurring on two of the lens materials rather than just one. This result indicates that the drying of the lens surface for 5 seconds out of solution has an effect on the deposition of tear components on certain lens materials. Thus, the model blink cell may be a useful tool for future deposition studies. Overall this thesis demonstrated that preparation of the lens material can cause variation in contact angles. Different methods of measuring in vitro wettability of contact lenses can produce different results and thus the method used to assess wettability should always be stated. The physical properties of blister pack solutions can change with added wetting agents and surfactants, and components from blister solutions can alter the initial wettability of contact lenses. In vitro deposition of proteins onto the lens surface can vary with techniques, and finally, deposition of tear components onto the surface of contact lenses can alter the lens wettability.

Microbial keratitis is the most serious, and only potentially blinding complication of contact lens wear. To further understand and reduce the risk of this disease, incidence rates and risk factors have been estimated in numerous studies. Since these studies were conducted, new lens types have been introduced designed to reduce the risk of infection. It was hypothesised that the issues of contact lens related hypoxia and poor lens hygiene could be addressed by the introduction of silicone hydrogel and daily disposable lenses respectively. This thesis describes the incidence of and risk factors for contact lens related microbial keratitis in Australia and New Zealand. The incidence of infection was determined by capturing all cases of contact lens related presumed microbial keratitis in a 12-month surveillance study, and by estimating the number of lens wearers using a population-based phone survey. Characteristics of the cases and controls were compared to estimate risk factors. In Australia, rates of infection with daily and overnight wear of hydrogel lenses were similar to previously published reports (1.9 [95%CI]:1.8-2.0] and 19.5 [95%CI:14.6-29.5] per 10,000 wearers respectively). Compared to the incidence of infection with hydrogel lenses, silicone hydrogel lenses had a higher rate in daily wear (11.9 [95%CI: 10.0-14.6]), and a similar rate in extended wear (19.5 [95%CI:14.6-29.5]). Daily disposable lenses had a similar rate of infection to daily wear of hydrogel lenses (2.0 [95%CI:1.7-2.4]), but appeared to reduce the incidence of severe or vision loss keratitis (0.5 [95%CI: 0.5-0.6] and 0.0 [95%CI: 0.0-0.0] respectively). Conducting the study in New Zealand confirmed the increase in incidence for overnight use of lenses, irrespective of lens type. Comparison of the incidence rates in New Zealand and Australia show that the rates in the two countries are comparable, bar an unexplained lower rate of infection for extended wear of soft hydrogel lenses in New Zealand. Risk factors for infection were overnight use of lenses, from occasional overnight to extended wear use, poor lens case hygiene, smoking, high socio-economic status and less than 6 months experience in current lens type. Amongst daily wearers, Internet or mail order purchasing of lenses was also associated with a higher risk of infection. This study is unique in terms of the study design and sample size, and the wide scope of risk factors considered. The determination of these incidence rates of infection and identification of risk factors is of extreme value to lens wearers and lens care practitioners around the world, particularly as the strongest and most prevalent risk factors are modifiable.

AIMS 1. To establish the patient demographics, risk factors, causative organisms, levels of antibiotic resistance, clinical presentations and treatment patterns of keratitis at a tertiary referral hospital in Australia. 2. To establish any change in these factors over 5 years. 3. Establish the factors associated with poor outcomes. METHODS: A retrospective audit of all patients who had a corneal culture in 5 years was conducted. Patients' clinical information was gathered from medical records and smear, culture and antibiotic resistance results were gathered from the local microbiology database. Associations between risk factors for keratitis and patient variables were analysed statistically. Outcome of a patient's episode of keratitis was classified as poor using final criteria. Trends over time in variables were analysed using linear regression. RESULTS: Two hundred and fifty-three (253) corneal cultures of 231 patients were included. Sixty percent (60%) of patients were male and there was a bimodal distribution in the age of presentation. Common risk factors for keratitis were contact lens wear (22%), ocular surface disease (18%), ocular trauma (16%) and prior ocular surgery (11 %). Corneal cultures were positive in 65% of cases and Pseudomonas aeruginosa (27%), coagulase-negative staphylococci (13%), Staphylococcus aureus (12%) and fungi (7%) were recovered. There was significant variation in the monthly recovery of P. aeruginosa (p=0.04) and fungi (p=0.02) which were more frequent in summer months, while Streptococcus pneumonia (p=0.04) was more common in winter months. Antibiotic resistance of cultured bacteria to cephalothin increased significantly (2% to 12%; p=0.02). Final vision of 6/12 or better was found in 48% (100) of cases while a poor outcome was seen in 28% (58) of cases. Multivariate analysis showed that the relative risk of a patient having a poor outcome was 4.3x (confidence interval [Cl] 2.0 to 9.5) if they had severe keratitis, 4.1 x (Cl 1.8 to 9.5) if they had keratitis related to ocular surface disease and 3.8x (Cl 1.8 to 8.3) if they were over 50 years old. CONCLUSIONS 1. In this series the most common risk factor for keratitis was contact lens wear and the most commonly isolated organism was P. aeruginosa which had seasonal variation in rate of recovery. 2. Keratitis related to contact lens wear became more frequent while keratitis related to prior ocular surgery became less frequent. 3. A poor outcome is more likely in patients with severe keratitis, keratitis related to prior ocular surface disease or older age.

Microbial keratitis is the most serious, and only potentially blinding complication of contact lens wear. To further understand and reduce the risk of this disease, incidence rates and risk factors have been estimated in numerous studies. Since these studies were conducted, new lens types have been introduced designed to reduce the risk of infection. It was hypothesised that the issues of contact lens related hypoxia and poor lens hygiene could be addressed by the introduction of silicone hydrogel and daily disposable lenses respectively. This thesis describes the incidence of and risk factors for contact lens related microbial keratitis in Australia and New Zealand. The incidence of infection was determined by capturing all cases of contact lens related presumed microbial keratitis in a 12-month surveillance study, and by estimating the number of lens wearers using a population-based phone survey. Characteristics of the cases and controls were compared to estimate risk factors. In Australia, rates of infection with daily and overnight wear of hydrogel lenses were similar to previously published reports (1.9 [95%CI]:1.8-2.0] and 19.5 [95%CI:14.6-29.5] per 10,000 wearers respectively). Compared to the incidence of infection with hydrogel lenses, silicone hydrogel lenses had a higher rate in daily wear (11.9 [95%CI: 10.0-14.6]), and a similar rate in extended wear (19.5 [95%CI:14.6-29.5]). Daily disposable lenses had a similar rate of infection to daily wear of hydrogel lenses (2.0 [95%CI:1.7-2.4]), but appeared to reduce the incidence of severe or vision loss keratitis (0.5 [95%CI: 0.5-0.6] and 0.0 [95%CI: 0.0-0.0] respectively). Conducting the study in New Zealand confirmed the increase in incidence for overnight use of lenses, irrespective of lens type. Comparison of the incidence rates in New Zealand and Australia show that the rates in the two countries are comparable, bar an unexplained lower rate of infection for extended wear of soft hydrogel lenses in New Zealand. Risk factors for infection were overnight use of lenses, from occasional overnight to extended wear use, poor lens case hygiene, smoking, high socio-economic status and less than 6 months experience in current lens type. Amongst daily wearers, Internet or mail order purchasing of lenses was also associated with a higher risk of infection. This study is unique in terms of the study design and sample size, and the wide scope of risk factors considered. The determination of these incidence rates of infection and identification of risk factors is of extreme value to lens wearers and lens care practitioners around the world, particularly as the strongest and most prevalent risk factors are modifiable.

Thesis (Ph. D.)--Ohio State University, 2004. / Title from first page of PDF file. Document formatted into pages; contains xiii, 122 p.; also includes graphics Includes bibliographical references (p. 80-94). Available online via OhioLINK's ETD Center

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Contact Lens Acute Red Eye (CLARE) and Infiltrative Keratitis (IK) are inflammatory responses of the eye associated with extended wear of soft contact lenses. Bacterial colonization of contact lenses with Gram-negative bacteria such as Pseudomonas aeruginosa is an important risk factor for the development of these adverse responses. Strategies that control the bacterial colonization of contact lenses may help prevent the occurrence of adverse responses. This thesis aimed to develop an animal model of CLARE/IK to test this hypothesis and to test the effectiveness of contact lenses containing antimicrobial compounds, namely silver and furanone compounds, in controlling corneal inflammation caused by Pseudomonas aeruginosa. A guinea pig model of contact lens wear was developed for the study and it was observed that the ocular responses to contact lens wear in the guinea pig were similar to those seen in human eyes wearing contact lenses. Also, three different models for CLARE/IK were developed and tested in the guinea pig eye. The pathological features of CLARE/IK in the guinea pig were virtually identical to those observed in human eyes. Bacterial contamination of contact lenses was confirmed to be a major risk factor for the development of CLARE/IK. Contact lenses containing nano-particles of silver demonstrated very good antibacterial activity against Pseudomonas aeruginosa in-vitro. The silver lenses were able to control the development of CLARE/IK responses in one of the models for CLARE/IK. Silver lenses might be most effective if used to prevent the establishment of a biofilm of bacteria on a lens such as might occur during storage in a contact lens case. Contact lenses were coated with different concentrations of the furanone compounds by physical adsorption and demonstrated good antibacterial activity at higher concentrations. However these concentrations were cytotoxic in-vitro and lower concentrations of furanones did not possess adequate antibacterial activity to control CLARE/IK responses in-vivo. This thesis has successfully demonstrated that guinea pigs can be used to test the effects of extended wear of contact lenses and developed models to test the pathogenesis of adverse responses such as CLARE/IK. The CLARE/IK models developed could be used to further our understanding of the pathogenesis of these inflammatory conditions and explore the activity of other antimicrobials.

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.

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.