Amblyopia is the leading cause of visual impairment in children (Wu and Hunter, 2006). In patients for whom the two eyes do not receive balanced visual input during the critical period in early development, the eye receiving less visual input ends up failing to represent its visual space in the brain. If the visual deprivation is corrected too late, the critical period closes, and patients are left with a lifelong deficit in visual acuity from the affected eye. The visual deficit is often quite severe, leaving a significant clinical problem to be addressed. Fortunately, great strides have revealed some of the molecular basis for critical period closure, raising the possibility of reopening the critical period in inadequately treated amblyopic patients. It is not known, however, whether the visual pathway axonal projections to the cortex persist after critical period closure in amblyopic patients. Any cortically directed drug treatment to reopen the critical period would strongly depend on the structural persistence of the visual pathway, particularly the geniculo-cortical optic radiations.
We hypothesize that the visual pathway from the eye to the brain through the LGN is not normal, that structural abnormalities will persist in the adult amblyopic patient, and that successfully treated amblyopic patients will demonstrate “normalized” brains. To test these hypotheses we will apply new structural imaging techniques to amblyopic children and adults in 3 aims. In Aims 1 and 2 we will ask, is there a quantitative difference in the visual pathways between amblyopic versus normal patients, in children or in adults? In Aim 3 we will ask, is the visual pathway of a successfully treated amblyopic child or adult similar to the untreated amblyopic visual pathway or to the normal visual pathway? In other words, does successful treatment restore normal structure to the amblyopic visual pathway?
For all 3 aims, we will examine the visual pathway at 3 points. Briefly, using high-resolution MRI, we will examine the volume of the lateral geniculate nucleus (LGN) of the thalamus. Using diffusion-tensor MRI (DT-MRI), we will examine the volume and organization of the white matter tracts entering (via the optic tract) and exiting (via the geniculo-cortical tract) the LGN. Our hope is to create and validate new imaging modalities for determining diagnosis and prognosis in this devastating disease.