Beyond ganglion cells: Novel foveal avascular zone features in MS with implications for vision loss

PROJECT SUMMARY Multiple sclerosis (MS) is a devastating neuro-degenerative disease that causes visual impairment in young, middle aged and older adults with resulting substantial lost productivity and cost to society. Current thinking attributes vision loss in MS to death and dysfunction of the retinal ganglion cells (RGCs) that comprise the optic nerve. However, there is only weak correlation between visual function and RGC atrophy, and some patients without RGC atrophy have vision loss, suggesting that all relevant contributors to vision loss in MS have not been identified. We have discovered structural features in the foveal avascular zone (FAZ) of retinas of the majority people with MS and a minority of people with glaucoma that cast a shadow on the photoreceptor layer and correlate with visual function. Our discovery contributes to addressing gaps in understanding visual pathway involvement in MS, offering new windows into diagnosis and treatment of vision loss in MS. This project studies the recently discovered FAZ features in retinas of people with MS and related diseases using adaptive optics scanning light ophthalmoscopy, a high resolution, non-invasive, state-of-the-art imaging technique. In the first aim, the relationship between central visual function and FAZ features will be defined using MS as an experimental model. Advanced microperimetry will be used to test the hypothesis that photoreceptor shadowing is the mechanism of vision loss. In the second aim the cause and composition of the FAZ features will be inferred through longitudinal studies of people with MS, cross sectional comparison between MS, glaucoma and related neurological and ophthalmic diseases and histopathological study of ex-vivo MS eyes. In the third aim rapid imaging protocols will be developed to enable faster detection of FAZ features and these will be applied to estimate the distributions of FAZ features in the populations with MS, glaucoma, other diseases and controls. These observations will evaluate the candidacy of the FAZ features as biomarkers of MS by defining specificity. The immediate impact of this research will be advancing understanding of vision loss in MS, developing rapid imaging strategies to enable broader study of large sample sizes at multiple sites and evaluating FAZ features as biomarkers in MS, glaucoma and other disease.