Eye disorders are on the rise as a result of an ageing population, an increasing obesity problem and a growth in the number of diabetic patients. Conventional ophthalmic formulations do not maintain therapeutic drug concentration in the target tissues for a long duration due to the physiological and anatomical eye barriers. Novel delivery systems such as nanoparticles have been explored to enhance the delivery of therapeutic agents to the eye. These delivery systems have in general been assessed using in-vivo animal models, despite ethical concerns for animal wellbeing. The aims of this thesis were to synthesise and characterise four amphiphilic polymers, subsequently prepare and characterise four nano sized polymeric self-assemblies loaded with triamcinolone acetonide (TA), develop an in-vitro porcine eye model and to evaluate the permeation of nano sized self-assemblies using the developed model. Four comb-shaped amphiphilic polymers (Pa5, Pa5-MPEG, Ch5 and Da10) were synthesised with a high yield (>81%) and good reproducibility. These polymers formed spontaneous positive self-assemblies in aqueous media (114-314 nm). The mean hydrodynamic diameters of the positive spontaneous self-assemblies entrapping TA were in the range of 200–334 nm loading high concentrations (455-1263 μg mL-1) of TA, much greater than the TA inherent aqueous solubility or concentrations achieved using conventional solubilisers. A porcine in-vitro eye model was developed to assess drug permeation through anterior and posterior ocular tissues. The model was partially validated using tritiated water and a series of hydrophilic markers with increasing molecular weights. The integrity of porcine ocular tissue was checked by monitoring the permeation of tritiated water to ensure the membrane intactness. Tritiated water permeation at 15 min was exploited as a potential method to normalise drug flux, as tritiated water percentage permeation at 15 min had an inverse relationship with tissue thickness (R2 = 0.66), to reduce the inherent variability between tissue samples thus increasing the accuracy of the in-vitro eye model. Four markers (fluorescein sodium salt, 4, 10 and 20 kDa FITC-dextran) were used for the purpose of investigating the effect of increasing molecular weight on ocular tissue permeability. The permeability of the markers displayed an inverse relationship and abrupt decline with Mw in terms of the permeability through scleral and corneal tissues of human and porcine and the molecular weight of the markers. The developed porcine in-vitro eye model showed good correlation with the human in-vitro model providing strong evidence it can be used to screen potential formulations before testing in-vivo. The TA loaded self-assemblies and a few chemical enhancers (glutamic acid, tween 80, chitosan, Pa5 and elevate temperature (45 °C)), selected to assist drug delivery via two routes (paracellular and transcellular), were tested using the developed in-vitro eye model. The results showed there was no marker permeation enhancement effect in porcine and human ocular tissues using chemical enhancers. In summary, a porcine in-vitro eye model was developed to assess hydrophobic and hydrophilic penetrant permeation across anterior and posterior ocular tissues. The porcine in-vitro eye model showed good correlation with the human in-vitro model providing strong evidence that the porcine in-vitro eye model can be used to screen potential formulations before testing in-vivo using the porcine model which ultimately might correlate well with the in-vivo human responses. Although TA self-assemblies did not significantly increase drug flux through human or porcine scleral tissues, it might be of interest for ophthalmic topically administered formulations due to their positive charge and small nano size.

The purpose of this thesis is to describe the development of an anatomically based, young adult eye model, which includes a crystalline lens with a gradient refractive index (GRIN). This model will then be used to investigate the effect of laser refractive surgery. The first step in this process involved developing a symmetrical eye model that was found to be a better predictor of empirical longitudinal spherical aberration than any previous model. Myopia was simulated by either a purely axial or refractive technique. While these models were found to be good predictors of the spherical aberration measured in young adults, they did not predict the total amount of high-order aberrations. The techniques used to simulate a single type of myopia caused the myopic models to become anatomically inaccurate. To improve the eye models a biconic surface was used to quantify the anterior corneal shape as a function of myopia. A method to describe the refractive error and biconic shape parameters in Jackson Cross Cylinder terms was implemented to determine correlations. Results indicate that a biconic accurately models the average shape of the anterior corneal surface as a function of myopia. Adopting the biconic model for the anterior corneal surface and adding average misalignments of the ocular components transformed the models from symmetrical to asymmetrical. Refractive error was now simulated by the anatomically accurate changes in both the anterior corneal shape and axial length. The asymmetrical aberrations resulted from the misalignment of the ocular components and provided a good prediction of average empirical aberrations but underestimated the aberrations of individual subjects. Photorefractive keratectomy, a form of laser refractive surgery, was simulated by theoretically calculated and by empirically measured changes in the shape of the anterior corneal surface. Applying the change in anterior corneal shape to the asymmetrical models was used to develop postoperative models. Changes in corneal shape and model aberrations attributed to theoretical calculations do not match empirical observations. The prediction of increased high-order aberrations in postoperative models based on empirically measured changes in the anterior corneal topography was similar to clinical results. Average anatomically based, GRIN eye models have been developed that accurately predict the average aberrations of emmetropic and myopic young adults. These models underestimate the asymmetrical and total high-order aberrations that have been measured in individual subjects but are still useful for investigating the average effects of procedures like refractive surgery.

The purpose of this thesis is to describe the development of an anatomically based, young adult eye model, which includes a crystalline lens with a gradient refractive index (GRIN). This model will then be used to investigate the effect of laser refractive surgery. The first step in this process involved developing a symmetrical eye model that was found to be a better predictor of empirical longitudinal spherical aberration than any previous model. Myopia was simulated by either a purely axial or refractive technique. While these models were found to be good predictors of the spherical aberration measured in young adults, they did not predict the total amount of high-order aberrations. The techniques used to simulate a single type of myopia caused the myopic models to become anatomically inaccurate. To improve the eye models a biconic surface was used to quantify the anterior corneal shape as a function of myopia. A method to describe the refractive error and biconic shape parameters in Jackson Cross Cylinder terms was implemented to determine correlations. Results indicate that a biconic accurately models the average shape of the anterior corneal surface as a function of myopia. Adopting the biconic model for the anterior corneal surface and adding average misalignments of the ocular components transformed the models from symmetrical to asymmetrical. Refractive error was now simulated by the anatomically accurate changes in both the anterior corneal shape and axial length. The asymmetrical aberrations resulted from the misalignment of the ocular components and provided a good prediction of average empirical aberrations but underestimated the aberrations of individual subjects. Photorefractive keratectomy, a form of laser refractive surgery, was simulated by theoretically calculated and by empirically measured changes in the shape of the anterior corneal surface. Applying the change in anterior corneal shape to the asymmetrical models was used to develop postoperative models. Changes in corneal shape and model aberrations attributed to theoretical calculations do not match empirical observations. The prediction of increased high-order aberrations in postoperative models based on empirically measured changes in the anterior corneal topography was similar to clinical results. Average anatomically based, GRIN eye models have been developed that accurately predict the average aberrations of emmetropic and myopic young adults. These models underestimate the asymmetrical and total high-order aberrations that have been measured in individual subjects but are still useful for investigating the average effects of procedures like refractive surgery.

The human eye is a complex optical system comprised of many components. The crystalline lens, an optical component with a gradient index (GRIN), is perhaps the least understood as it is situated inside the eye and as a result is difficult to characterize. Its complex nonlinear structure is not easily measured and consequently not easily modeled. Presently several models of the GRIN structure exist describing the average performance of crystalline lenses. These models, however, do not accurately describe the performance of crystalline lenses on an individual basis and a more accurate individual eye model based on anatomical parameters is needed. This thesis proposes an anatomically correct, individually customizable crystalline lens model. This is an important tool and is needed both for research on the optical properties of human eyes and to diagnose and plan the treatment of optically based visual problems, such as refractive surgery planning. The lens model consisted of an interior GRIN with a constant refractive index core. The anterior and posterior surface was described by conic sections. To realize this eye model, the optical and biometric properties of mammalian lenses were measured and the correlation relationships between these measurements were used to simplify the model down to one fitting parameter which controls the shape of the GRIN. Using this data, an anatomically correct individualizable model of the lens was successfully realized with varying parameters unique to each lens. Using this customizable lens model, customizable human eye models based on measurements of the entire human eye can be realized.

The human eye is a complex optical system comprised of many components. The crystalline lens, an optical component with a gradient index (GRIN), is perhaps the least understood as it is situated inside the eye and as a result is difficult to characterize. Its complex nonlinear structure is not easily measured and consequently not easily modeled. Presently several models of the GRIN structure exist describing the average performance of crystalline lenses. These models, however, do not accurately describe the performance of crystalline lenses on an individual basis and a more accurate individual eye model based on anatomical parameters is needed. This thesis proposes an anatomically correct, individually customizable crystalline lens model. This is an important tool and is needed both for research on the optical properties of human eyes and to diagnose and plan the treatment of optically based visual problems, such as refractive surgery planning. The lens model consisted of an interior GRIN with a constant refractive index core. The anterior and posterior surface was described by conic sections. To realize this eye model, the optical and biometric properties of mammalian lenses were measured and the correlation relationships between these measurements were used to simplify the model down to one fitting parameter which controls the shape of the GRIN. Using this data, an anatomically correct individualizable model of the lens was successfully realized with varying parameters unique to each lens. Using this customizable lens model, customizable human eye models based on measurements of the entire human eye can be realized.

The human eye is a complex optical system comprised of many components. The crystalline lens, an optical component with a gradient index (GRIN), is perhaps the least understood as it is situated inside the eye and as a result is difficult to characterize. Its complex nonlinear structure is not easily measured and consequently not easily modeled. Presently several models of the GRIN structure exist describing the average performance of crystalline lenses. These models, however, do not accurately describe the performance of crystalline lenses on an individual basis and a more accurate individual eye model based on anatomical parameters is needed. This thesis proposes an anatomically correct, individually customizable crystalline lens model. This is an important tool and is needed both for research on the optical properties of human eyes and to diagnose and plan the treatment of optically based visual problems, such as refractive surgery planning. The lens model consisted of an interior GRIN with a constant refractive index core. The anterior and posterior surface was described by conic sections. To realize this eye model, the optical and biometric properties of mammalian lenses were measured and the correlation relationships between these measurements were used to simplify the model down to one fitting parameter which controls the shape of the GRIN. Using this data, an anatomically correct individualizable model of the lens was successfully realized with varying parameters unique to each lens. Using this customizable lens model, customizable human eye models based on measurements of the entire human eye can be realized.

The human eye is a complex optical system comprised of many components. The crystalline lens, an optical component with a gradient index (GRIN), is perhaps the least understood as it is situated inside the eye and as a result is difficult to characterize. Its complex nonlinear structure is not easily measured and consequently not easily modeled. Presently several models of the GRIN structure exist describing the average performance of crystalline lenses. These models, however, do not accurately describe the performance of crystalline lenses on an individual basis and a more accurate individual eye model based on anatomical parameters is needed. This thesis proposes an anatomically correct, individually customizable crystalline lens model. This is an important tool and is needed both for research on the optical properties of human eyes and to diagnose and plan the treatment of optically based visual problems, such as refractive surgery planning. The lens model consisted of an interior GRIN with a constant refractive index core. The anterior and posterior surface was described by conic sections. To realize this eye model, the optical and biometric properties of mammalian lenses were measured and the correlation relationships between these measurements were used to simplify the model down to one fitting parameter which controls the shape of the GRIN. Using this data, an anatomically correct individualizable model of the lens was successfully realized with varying parameters unique to each lens. Using this customizable lens model, customizable human eye models based on measurements of the entire human eye can be realized.