Structural Imaging of the Amblyopic Brain

Lay Summary

Using Imaging to Improve Diagnostic and Prognostic Accuracy for the Visual Disorder Amblyopia

Researchers will use diffusion tensor imaging (DTI) to determine whether people with the vision disorder amblyopia have structurally or functionally impaired pathways from the eyes to the brain. This could be used to guide future treatment strategies.

Amblyopia is the leading visual impairment in children. In situations of misalignment, refractive error, or congenital cataract, one eye receives more visual information, becomes stronger, and commands more space in the visual cortex compared to the weak eye. Treatment with a patch or blurred glass over the strong eye before age nine, the critical window for developmental plasticity, enables the weak eye to gain equal spatial representation in the brain. Successful development of alternative or later-initiated treatments will depend on knowing whether the neural pathways from the eye to the visual cortex, through the “lateral geniculate nucleus” (LGN), are structurally abnormal, or just not functioning properly.

The researchers hypothesize that the pathways are abnormal, but are corrected by treatment. They will test this in a total of 30 children and adults in three groups, one previously treated effectively, one previously not treated effectively, and one visually healthy “control” group. Researchers will see if the LGN has less volume and disrupted organization in amblyopia and whether these abnormalities have been corrected in adults who had been effectively treated as children.

Significance:  Development of improved amblyopia treatment strategies will be aided by learning whether structural or functional visual pathway abnormalities occur. The study may demonstrate the utility of DTI imaging in improving the diagnosis and prognosis of amblyopia and other visual disorders.

Abstract

Structural Imaging of the Amblyopic Brain

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.