Fritsch, Dennis Manuel; (2018) Visual Impairment in the absence of ON-pathway signal. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Congenital retinal diseases are a major cause of childhood and lifelong visual im- pairment. Such conditions can manifest a variable array of severe and subtle ef- fects on vision. Assessment of visual function in children can be challenging; yet, knowledge about phenotype, genotype and impact of these disorders is crucial for providing appropriate support, tailored diagnostics and for developing treatments. ON-and OFF-pathways are separately transmitting information on brightness and darkness from the retina to the cortex, where their interplay is crucial in visual perception. This project investigated the effects of retinal ON-pathway dysfunction on vision. A cohort of 109 patients with ON-pathway dysfunction was examined from four subgroups of visual electrophysiological phenotypes (incomplete and complete Congenital Stationary Night Blindness - CSNB, Duchenne Muscular Dystrophy - DMD, and congenital disorders of N-glycosylation - PMM2-CDG). Using spe- cialised visual evoked potential stimuli, designed to distinguish the ON-and OFF- pathway signal arrival at the striate cortex, marked ON system delays were revealed in patients with subtypes of CSNB, DMD mutations post exon 30 and PMM2-CDG. A child-friendly psychophysical software called LumiTrack was developed to assess motion and contrast perception, two important qualities conveyed by ON-and OFF-pathways. Patients with subtypes of CSNB and PMM2-CDG showed abnormalities in motion perception and subnormal contrast sensitivity, while patients with DMD performed at the level of healthy volunteers. These impairments may occur due to a delay of signal transmission through the retina, resulting in an ON/OFF signal asymmetry within the visual system. A genotype-phenotype comparison suggested a trend of increasing ON/OFF asymmetry associated with genetic defects affecting proteins placed later within the photoreceptor / ON bipolar cell signalling cascade. This systematic study of cortical and behavioural visual function in patients with ON-pathway dysfunction highlights the impairments encountered by patients in visual qualities important for everyday life.

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