Doctor of Philosophy
Detecting ocular conditions and initiating treatment at the earliest is essential for preserving the remaining visual health in various ocular diseases such as glaucoma, diabetic retinopathy, and inner retinal diseases such as retinoblastoma. Ocular treatment strategies include topical administration of drugs (e.g., Timolol for glaucoma), ocular surgeries (e.g., trabeculoplasty), gene therapy (e.g., for treating age related macular degeneration), light-based (e.g., laser) therapies and direct injection (e.g., intravitreal injections) of drugs depending on the target site of the ocular therapy. Topical administration of drugs to the anterior segment and photothermal therapy of the posterior segment of the eye are among the least invasive ocular treatment strategies available. To develop treatment parameters, critical challenges are present in understanding the relationship among administered dosage levels, bioavailability at the target site and desired therapeutic response. Computational models and experimental animal studies are generally required before initiating clinical trials for assessing efficacy of candidate treatment strategies. Accurate but complex computational models of the eye and therapies are possible by incorporating appropriate physical as well as functional characteristics and laws those govern the structural, fluidic and functional behavior of the eye and the therapeutic procedures. In this dissertation, we have developed: 1) a new physiologically-based pharmacokinetic (PBPK)-pharmacodynamic (PD) computational model in which drug transport is guided by the biomechanical and the biofluidic environment of the eye as well as by the governing principles of drug diffusion through elastic solids and convective fluids; 2) a computational model of transport of charged gold nanoparticles injected into the vitreous humor for estimating the volume fraction of nanoparticles available in the posterior segment of the eye for therapy; and 3) a computational model of light transport and light-tissue interaction resulting in photothermal and thermomechanical changes including material phase change (vaporization and condensation) due to laser irradiation in the posterior segment with and without nanoparticles. The PBPK-PD model was validated using experimental data of rabbit eyes from a previous study (Sakanaka K, 2008); and our nanoparticle mediated retinal photocoagulation model was validated using experimental data of ex vivo porcine eyes from a previous study (Singh R, 2017). These computational models show promises for confirming mechanistic details of therapy and reducing animal testing needs in the early stages of treatment design; for identifying optimal treatment delivery routes; and for developing optimal treatment dosage levels. The predictive aspect of these computational models may provide insights and clues to newer experimental targets.
Dissertation or thesis originally submitted to ProQuest.
Chowdhury, Jabia Mostofa, "MULTIPHYSICS-BASED COMPUTATIONAL MODELING OF OCULAR THERAPEUTICS" (2022). Electronic Theses and Dissertations. 3285.