Investigation of the normal and pathological development of the macula of the infant human eye using high resolution Optical Coherence Tomography (OCT)

The fovea is a specialised retinal area responsible for high spatial vision. Development of the fovea involves centrifugal migration of inner retinal layers (IRLs) away from the fovea and centripetal displacement of the cone photoreceptors into the fovea and is thought to be complete by 5 years of age. Current understanding of human foveal development is limited to studies of few histological specimens. The recent development of hand-held spectral domain optical coherence tomography (HHSDOCT), can overcome this limitation by facilitating large scale in vivo imaging of the infant human retina, both in controls and in conditions such as achromatopsia and albinism, where foveal development is disrupted. In this thesis, we optimise image acquisition and analysis with HH-SDOCT in young children with nystagmus. We show that HH-SDOCT is reliable in children with and without nystagmus, with an intraclass correlation coefficient of 0.96 for central macular thickness measurements. The non-linear developmental trajectories of each retinal layer modelled in a large cohort of 256 controls suggest that development continues until 12 years of age. A paradigm for the etiological diagnosis of nystagmus using OCT is presented. We describe multiple abnormalities of retinal development in young children with achromatopsia and albinism, including delayed regression of the IRLs from the fovea, diminished elongation of the photoreceptor layers with age and a reduction in perifoveal retinal thickness. This results in significantly increased IRL and decreased photoreceptor thicknesses at the fovea in both conditions (p < 0.05). In contrast, the IRL thickness is significantly decreased at the perifovea in both achromatopsia and albinism (p < 0.01). There is evidence of postnatal development in the achromat and albino retina. In achromatopsia, disruption of photoreceptors is progressive with age. With gene therapy imminent, potentially earlier treatment of these conditions may normalise retinal development and optimise vision.