SYNAPTIC: Structural, Functional and Chemical Assessments of the Visual Pathway in Retinal Disease.

Retinal diseases including age-related macular degeneration (AMD) and retinitis pigmentosa (RP), have been associated with significant secondary structural changes to the posterior visual pathway. What has yet to be established is whether such cortical changes reflect atrophy (cortical shrinkage), demyelination (reduced axon myelination) and/or degeneration (cell death). Understanding the effects of retinal disease on the entire visual pathway and how this may differ with the type of retinal disease, will aid future techniques aimed to restore visual input and patient selection for such treatments In this thesis, novel magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) protocols were employed to quantify changes to the posterior visual pathway, specifically whether there is evidence of cortical atrophy, degeneration, or demyelination in retinal disease. Outcome measures from the anterior and posterior visual pathways were correlated to investigate potential biomarkers of disease progression. The penultimate chapter investigated how the Argus® II retinal prosthesis affects the structure and function of the visual cortex. Chapters two and three reveals that significant cortical atrophy of the entire occipital cortex is observed in long-term unilateral and bilateral AMD. Pilot data from a small cohort of long-term bilateral RP patients, suggest some patients show signs of atrophy whilst other do not, although a larger sample is needed to draw definitive conclusions. Moreover, there were no significant signs of cortical degeneration or demyelination were observed in either retinal disease. Chapters four and five reveal that reduced macular thickness, specifically the ganglion cell layer (GCL), is observed in both retinal diseases suggesting degeneration of the retina. Monitoring GCL thickness may be a sensitive biomarker of disease progression. This thesis also revealed that reduced cortical thickness in the occipital pole significantly predicts visual acuity performance in AMD, the first study to report such a finding. Finally, in an individual AMD patient implanted with the Argus® II, 13-months post-surgery there was a very modest increase in cortical thickness of the occipital cortex yet diminished stimulus-driven responses. The success of restoring visual input in this case may well have been limited by the substantial cortical atrophy observed pre-surgery.