Understanding and Treating Eye Diseases: Mechanical Characterization and Photochemical Modification of the Cornea and Sclera

Citation

Mattson, Matthew Sanford (2008) Understanding and Treating Eye Diseases: Mechanical Characterization and Photochemical Modification of the Cornea and Sclera. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/DXGR-GV57. https://resolver.caltech.edu/CaltechETD:etd-05282008-163501

Abstract

Proper vision depends on the physical properties of the eye tissues. Diseases that alter the chemical and mechanical states of the tissue can result in a loss of functionality. Degenerative myopia and keratoconus are diseases that exhibit such changes in the sclera and cornea, respectively. These diseases may be treatable by engineering the mechanical properties of the sclera and cornea.

We have developed an intact globe expansion method for mechanical characterization of eyes in vitro, which provides reliable measurements, with relatively few samples, and mimics the type and distribution of stresses inherent in the natural boundary conditions of the eye. Furthermore, application of high intraocular pressures provides a way to study shape changes of the sclera and cornea which are similar to those exhibited in myopia and keratoconus. Potential treatments that show an ability to prevent ocular distension in this method have a chance of preventing the deformations that occur in vivo in the diseases.

Our studies in vitro indicate that crosslinking can improve tissue mechanical stability and resistance to deformation. Light activated crosslinking provides spatial and temporal control of treatments, and photoinitiator systems such as Eosin Y (EY) and triethanolamine (TEOA) allow this control with safe doses of visible light.

For myopia treatment, we demonstrate in vitro stabilization of eyes using the intact globe method after drug is delivered to the sclera in vitro or in vivo on 2–3 week old rabbits. Biocompatibility studies of the scleral treatments indicate excellent tolerance to the light and drug in both rabbits and guinea pigs. Further, we have developed treatment protocols for use in a guinea pig form-deprivation model of myopia. In normally growing guinea pig eyes, treatments can create substantial changes to eye shape. These changes are manifested in shifts in the refractive error and ocular length that persist for the duration over which the animals are monitored.

For keratoconus, treatment in vitro on rabbit eyes using EY/TEOA demonstrates similar capabilities of corneal stabilization as a treatment currently in clinical trials. The EY/TEOA treatment shows advantages of reduced treatment time and the possibility of treatment without removal of the epithelium.

Thesis Files