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.

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.

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Accessing the inner ear presents a significant challenge for the diagnosis and treatment of inner ear diseases. Many existing techniques to access the inner ear are invasive and can cause permanent damage to the cochlea. Recently, a novel microneedle has been fabricated to perforate the round window membrane (RWM) – a membrane sealing one of the two openings in the cochlea. These perforations enhance drug delivery into the inner ear, potentially improving the efficacy of therapeutics. Furthermore, they allow for the aspiration of perilymph samples, which is essential for diagnosing inner ear diseases. However, owing to limited knowledge about the mechanical properties of the RWM, certain technical aspects remain unexplored. Specifically, the interaction between the RWM and the microneedle during perforation is yet to be examined. This investigation is pivotal for the optimal design of microneedles — those robust enough to perforate RWMs yet delicate enough to minimize damage. In this thesis, we conduct a thorough examination of the guinea pig RWM, encompassing its geometry and its mechanical responses to pressures from the middle ear and inner ear. Additionally, we also formulate a comprehensive constitutive law for the guinea pig RWM. Our exploration begins with the creation of a U-Net model tailored to automatically segment the RWM. Despite the presence of other structures in the same image—such as bone, the basilar membrane, and ambient noise—the model proved invaluable for efficiently and automatically segmenting the RWM. To enhance accuracy, post-processing techniques like connected component analysis and majority voting were incorporated. Using this 3D model, we proceeded to study the RWM’s geometry. Recognizing the shrinkage observed in fixed RWMs, we integrated fresh RWM data to estimate the shrinkage ratio. Subsequently, we analyzed both the overall RWM thickness and that of the middle connective tissue layer—crucial metrics for future RWM modeling. Next, we proposed a method to evaluate the in-plane deformation of the RWM due to applied pressure. This involved using a bulge test system to pressurize and deform the RWM, combined with confocal microscopy to track stained nuclei or pre-introduced fluorescent beads on the RWM. We then utilized the coherent point drift (CPD) algorithm to measure the displacement of beads and nuclei. Results indicated that both markers could be successfully used to measure the RWM’s displacement. Further analysis revealed the in-plane Lagrangian strain of the RWM, with a significant observation being that the direction of maximum in-plane Lagrangian strain is perpendicular to the fiber direction. This underscores the crucial role of collagen fibers in determining the RWM’s mechanical properties. To conclude our study, we devised a constitutive law for the RWM, conceptualizing it as a combination of the ground substance and a family of dispersed fibers. This model was integrated into a FEBioStudio plugin, facilitating simulations of the RWM’s mechanical reactions to different pressures. Although our simulations closely aligned with experimental findings, some discrepancies were noted, likely stemming from an incomplete understanding of fiber dispersions. Nevertheless, our constitutive law reinforces the notion that fibers primarily govern the RWM’s mechanical characteristics.