Phototherapeutic Devices for the Treatment of Diabetic Retinopathy

Citation

Cook, Colin Andrew (2019) Phototherapeutic Devices for the Treatment of Diabetic Retinopathy. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/62R5-RF78. https://resolver.caltech.edu/CaltechTHESIS:01102019-190818557

Abstract

Diabetic retinopathy is a microvascular disease of the retina and a leading cause of vision loss worldwide. In the non-proliferative phase, diabetes-induced degradation of the retinal blood supply leads to edema and progressive tissue hypoxia. In response, the retinal tissue expresses proangiogenic growth factors (e.g. vascular endothelial growth factor), which drive proliferation of aberrant blood vessels within the eye. These poorly formed vessels leak fluid and blood cells into the eye and grow into the vitreous, which puts traction on the retina and leads to detachment. Given the hypoxic etiology, retinal oxygen tension and metabolism have received considerable attention. Dark-adapted conditions drive the retina to a significantly lower oxygen tension compared to light- adapted conditions as rod cells consume more energy in order to boost sensitivity. While tolerable in the healthy retina, it has been hypothesized that increased nightly metabolism overwhelms the compromised oxygen supply in the diabetic retina, leading to hypoxia and pathological vascular endothelial growth factor expression.

This thesis develops ocular devices that shine light onto the retina to modulate rod metabolism, reducing oxygen demand and mitigating nightly hypoxia. The phototherapeutic effect is characterized through mathematical modeling of retinal metabolism and in vivo testing. Implantable phototherapy devices are designed, fabricated, and evaluated. This thesis also develops overnight phototherapeutic contact lenses utilizing radioluminescence, chemiluminescence, and electroluminescence approaches. Phototherapy holds promise as a non-invasive, preventative therapy for the treatment of hypoxic retinal diseases such as diabetic retinopathy.

Thesis Files