Developing hyperspectral OCT as a clinical test to detect neural dysfunction in degenerative diseases of the optic nerve and retina

The retina and optic nerve are the only parts of the central nervous system that can be easily visualized non-invasively. A limitation with conventional optical imaging technology is that substantial degree of neuronal loss in the retinal and optic nerve structure and function has to occur before the disease is detected. This is true for glaucoma and diabetic retinopathy, as well as ocular changes associated with brain diseases such as Alzheimer’s disease and Parkinson’s disease. Hence, there is a need for novel investigational techniques that can better inform us on the state of neural health status. This will then allow for timely diagnosis of eye diseases and exploit the eye as a “window” to identifying sick and dying nerve cells in the brain. In the present grant, we propose to set up a novel hyperspectral optical coherence tomography (OCT) technique to fill this gap. We have obtained preliminary data using hyperspectral fundus imaging, demonstrating that such characteristic disease signatures can be obtained in principle. However, in contrast to fundus imaging, our approach provides depth resolution thereby increasing sensitivity and specificity. We first plan to set up a custom-built hyperspectral OCT system. Using hyperspectral analysis of the OCT system, we propose to identify characteristic signatures in animal models of the disease. Based on the experience with the initial laboratory-based set-up, we plan to further develop a second hyperspectral OCT prototype that will also be used for the clinical proof-of-concept studies. The final aim of this grant is to establish hyperspectral OCT, as a specific and sensitive biomarker for the early detection of inner retinal changes associated with retinal ganglion cell dysfunction. This may have important implications for early diagnosis and follow-up of neurodegenerative disease, and the technique may also provide a novel surrogate outcome for neuroprotection studies.