No description available.

The ocular surface is extremely effective at protecting the eye through such physiological barriers as the cornea and tear film. The exposed nature of the cornea can still lead to a significant number of injuries and harm from the external environment. Management and treatment of ocular injuries involves a combination of a bandage contact lens (BCL) along with therapeutic eye drops that require frequent and strict dosing regimens that can be difficult to maintain and are inefficient due to the high clearance rate of the eye. Therapeutic contact lenses (TCL) with vitamin E (VE) incorporated have been shown to steadily release a desired therapeutic agent and potentially simplify a patient’s treatment process. Vat polymerization (VP), a form of 3D printing, was utilized in this work to explore a platform design for developing customizable VE-containing TCLs, using dexamethasone phosphate (DXP) as a model drug. VP was also used to explore the creation of a multi-material TCL, using a VE embedded ring that could be directly printed within the lens in a streamlined and automated manner. Three lens formulations consisting primarily of hydroxy ethyl methacrylate (HEMA) and polyethylene glycol diacrylate (PEGDA) with modified formulations containing methacrylated VE (VEMA) and Methacryloxypropyltris (Trimethylsiloxy) silane (TRIS) as a model silicone material were prepared. These lenses were synthesized and characterized to examine 3D printing for lens creation in comparison to commercial standards. The base and VEMA formulations were used to examine the feasibility of a multi-material (MM) lens with an embedded ring directly incorporated during the printing process. All three formulations showed shear thinning properties suitable for VP bioprinting applications. The base formulation produced a very homogenous print while VEMA prints showed defects and clear phase separation. The VEMA+TRIS formulation showed significant improvement as the prints were more homogenous with fewer defects. The MM lenses showed a mixture of properties between the base and VEMA formulations, with the center appearing more homogenous and the edge that included the embedded ring showing defects similar to VEMA prints. Surface wettability and water content decreased from the base formulation with an increasing presence of hydrophobic moieties in the modified formulations. The increased hydrophobicity can be correlated with an increase in stiffness seen from the base formulation. While all materials had high moduli due to the high crosslinking density and presence of PEGDA, the VEMA prints had a higher modulus than the base material but were quite brittle due to the increased hydrophobicity and poor print quality. The VEMA+TRIS prints showed a significant (p < 0.05) increase in stiffness without the brittleness of the VEMA prints due to the better print quality. The MM prints had the lowest moduli, most similar to the base material, indicating that this lens design could mitigate the brittleness seen with the VEMA prints. A comparison of 3DP and casting showed the cast material having a significantly (p < 0.05) higher modulus than the 3DP material presumably due to the bulk vs. layer-by-layer polymerization processes that the respective manufacturing methods utilize. The base material produced significantly more transparent prints, with transmissions (wavelength) that ranged between 80-88%, compared to the VEMA and VEMA+TRIS prints which ranged from 18-47%. The MM lenses showed promise for minimizing the effect of the poor transparency of the VEMA ring with transparency of 62-85%. Besides the formulations, the lens thickness, print quality and print plate surface were found to be major contributors to the printed lenses not meeting commercial standards. The VEMA+TRIS loaded lenses showed the greatest changes in the release kinetics with a larger burst release, attributed to the weaker affinity DXP has to the hydrophobic components, while the base and VEMA lens’ profiles were very similar. The weaker drug-polymer interaction and more mobile silicone-oxygen bonds of TRIS are likely the reason for the VEMA+TRIS formulation releasing significantly more DXP than the base or VEMA lenses, with 69.21 ± 3.62%, 44.09 ± 4.63% and 37.09 ± 4.81% released respectively. It is believed that the high degree of crosslinking within the lens polymer matrix causes high levels of physical entrapment, resulting in an incomplete release of DXP from the lenses. Another possibility is that some DXP reacted with the acrylate components of the lens formulations as the photopolymerization process creates free radicals which could lead to the formation of covalent bonds of DXP with one of the monomers in the formulation. The use of 3DP to develop customizable TCLs on-demand has a lot of potential as the biomedical and healthcare industries shift to more of a personalized rather than a one-size-fits all approach. The MM lens design allows for the incorporation of materials with poor lens properties without significantly impacting the lens’ functions such as its tensile stiffness and transparency. The freedom of design that 3DP provides will allow for tailor-made lenses that can meet a patient’s specific needs, including lens fitting, which would maximize the patient’s comfort. / Thesis / Master of Applied Science (MASc)

No description available.

Purpose: To examine the variables that influence lipid deposition on conventional and silicone hydrogel contact lens materials and to build a physiologically relevant in vitro model of lipid deposition on contact lenses. Methods: Lipid deposition on contact lens materials can lead to discomfort and vision difficulty for lens wearers. Using a variety of radiochemical experiments and two model lipids (cholesterol and phosphatidylcholine), a number of clinically significant parameters that may influence lipid deposition were examined. • The optimization and characterization of a novel artificial tear solution (ATS) was examined (Chapter 3) • Optimization of an extraction system to remove deposited cholesterol and phosphatidylcholine from various contact lens materials (Chapter 4) • The influence of different tear film components on lipid deposition was researched (Chapter 5) • The efficiency of hydrogen peroxide disinfecting solutions to remove deposited lipid from contact lenses was investigated (Chapter 6) • The effect of intermittent air exposure on lipid deposition was examined through the use of a custom built “model blink cell” (Chapter 7) Results: A novel complex ATS designed for in-vial incubations of contact lens materials was developed. This solution was stable and did not adversely affect the physical parameters of the contact lenses incubated within it. An efficient extraction protocol for deposited cholesterol and phosphatidylcholine was optimized based on chloroform and methanol with the addition of water and acetic acid for phosphatidylcholine extraction. Overall, cholesterol and phosphatidylcholine deposition is cumulative over time and found to deposit in greater masses on silicone-containing hydrogels. Cholesterol and phosphatidylcholine deposition is influenced by the composition of the incubation medium and air exposure which occurs during the inter-blink period. Hydrogen peroxide disinfecting solutions were able to remove only marginal amounts of lipid from the contact lenses, with the surfactant containing solution removing more. Conclusion: This thesis has provided hitherto unavailable information on the way in which lipid interacts with conventional and silicone hydrogel contact lens materials and the in vitro model built here can be utilized in various ways in the future to assess other aspects and variables of lipid and protein deposition on a variety of biomaterials.

The aim of this thesis was to design, develop and evaluate a Non-Contact Corneal Aesthesiometer (NCCA), using a controlled pulse of air, of a pre-determined pressure. First, the system design and alterations are described, then in a series of model experiments, the standardisation and characteristics of the air-pulse were examined. These studies revealed that the NCCA could produce a repeatable stimulus of known volume and rate of air-flow. Furthermore, the air-flow exiting the stimulus air jet was of a laminar shape, with minimal dispersion. The control of the air-flow dispersion was further enhanced by using a 0.5mm diameter air jet and a working distance of lcm. Varying the stimulus duration was not found to influence these qualities of the air-pulse. The air-pulse stimulus was shown to possess the ability to produce corneal nerve stimulation either by surface deformation, temperature change, or both. Using thermal imaging equipment, a temperature drop in the ocular tear film was demonstrated that was localised, and limited to the cornea. A second series of experiments investigated the ability of the NCCA to measure a corneal sensitivity threshold. These studies indicated that a forced-choice, doublestaircase, Method of Limits experimental technique produced an accurate threshold, with low variability in the results, over a minimum time period. Further studies showed that this threshold measurement was repeatable to within 0.1 mbars. A database of typical normal sensitivity thresholds, under a number of physiological variables - corneal location, gender, age and iris colour, was developed. The results from these studies compared well qualitatively with those using invasive stimuli. A third series of experiments examined the ability of the NCCA to assess corneal nerve function when it was under a number of external influences. The first situation was that of anaesthesia,p roduced by 0.4% benoxinate hydrochloride. Non-contact corneal sensitivity loss and recovery were shown to return to normal levels 60mins after instillation of the anaesthetic. The second situation was that of long-term contact lens wear (i.e. longer than three years). Non-contact sensitivity was shown to be reduced with both soft and gas-permeable lens wear, although the extent of loss did not differ between them, nor was it influenced by the length of wear. Thirdly,corneal sensitivity loss and recovery was assessed in subjects following excimer laser photorefractive keratectomy (PRK). Three laser trials were completed: a longitudinal myopic study, a transverse myopic study, and a longitudinal hyperopic study. The results indicated that non-contact corneal sensitivity loss/recovery was not related to the attempted depth of ablation, and that sensitivity had still not returned to normal levels one year post-op.

Purpose: To examine the variables that influence lipid deposition on conventional and silicone hydrogel contact lens materials and to build a physiologically relevant in vitro model of lipid deposition on contact lenses. Methods: Lipid deposition on contact lens materials can lead to discomfort and vision difficulty for lens wearers. Using a variety of radiochemical experiments and two model lipids (cholesterol and phosphatidylcholine), a number of clinically significant parameters that may influence lipid deposition were examined. • The optimization and characterization of a novel artificial tear solution (ATS) was examined (Chapter 3) • Optimization of an extraction system to remove deposited cholesterol and phosphatidylcholine from various contact lens materials (Chapter 4) • The influence of different tear film components on lipid deposition was researched (Chapter 5) • The efficiency of hydrogen peroxide disinfecting solutions to remove deposited lipid from contact lenses was investigated (Chapter 6) • The effect of intermittent air exposure on lipid deposition was examined through the use of a custom built “model blink cell” (Chapter 7) Results: A novel complex ATS designed for in-vial incubations of contact lens materials was developed. This solution was stable and did not adversely affect the physical parameters of the contact lenses incubated within it. An efficient extraction protocol for deposited cholesterol and phosphatidylcholine was optimized based on chloroform and methanol with the addition of water and acetic acid for phosphatidylcholine extraction. Overall, cholesterol and phosphatidylcholine deposition is cumulative over time and found to deposit in greater masses on silicone-containing hydrogels. Cholesterol and phosphatidylcholine deposition is influenced by the composition of the incubation medium and air exposure which occurs during the inter-blink period. Hydrogen peroxide disinfecting solutions were able to remove only marginal amounts of lipid from the contact lenses, with the surfactant containing solution removing more. Conclusion: This thesis has provided hitherto unavailable information on the way in which lipid interacts with conventional and silicone hydrogel contact lens materials and the in vitro model built here can be utilized in various ways in the future to assess other aspects and variables of lipid and protein deposition on a variety of biomaterials.

No description available.

No description available.

The launch of silicone hydrogel contact lenses has led to a rise in the incidence of mechanically-related clinical complications, which is thought to be due to the increased stiffness of these materials compared to conventional hydrogel lens materials. The mechanical characteristics of hydrogel contact lenses have traditionally been investigated using tensile testing which investigated the bulk material characteristics. This thesis presents a study intended to establish a repeatable method for local mechanical measurement of hydrogel contact lenses using nanoindentation. Hydrogel materials in phosphate buffered saline were indented using a Hysitron Triboindenter mounted on a Veeco Explorer AFM using Triboscope software (version 3.5a) with a specially constructed wet cell. A model hydrogel (poly(HEMA-MMA)) was used to validate the methodology and investigate a the effect of controlled change in specimen thickness. A range of commercially available hydrogel contact lenses were then characterised (including conventional and silicone hydrogel lenses) using the same method. Two different analytical techniques were employed to determine the mechanical properties data; elastic analysis and a time-dependent viscoelastic analytical technique.A strong influence of specimen thickness on apparent mechanical properties was seen with the elastic analysis and an empirical relationship was derived to correct for this which was found to be appropriate for all contact lens specimens studied and reported in the thesis. The viscoelastic analysis results were more complex and exhibited a less clear influence of specimen thickness. However, as this is a very simple approximation as contact lenses are suspected to be poroelastic rather than viscoelastic this work could not be fully resolved in the scope of this thesis. For all contact lenses analysed, nanoindentation produced data similar to that found with conventional tensile testing, however, there was evidence for a slight dependence of elastic properties across the lens that does not correlate with sample thickness. This thesis shows the development of a way of accounting for the variation of thickness of a range of contact lenses, and demonstrated that traditional analysis is accurate enough to determine local differences in modulus across contact lenses. The viscoelastic analysis may be more appropriate for hydrogels, however, it produced irregularities that will require further work to fully resolve.

No description available.