1.Crossed Eyes in Infancy (Infantile Esotropia) is a health condition with an incidence of 8.3 per 100,000 children 18 years of age or under. Contrary to the popular belief that crossed eyes is a purely cosmetic condition, children born with crossed eyes suffer from a number of visual and eye movement impairments. Our goal is to understand the brain mechanisms that cause crossed eyes and to find a cure for it. Specifically, our research aims to answer three major questions: (1) How do the brain circuits that control vision and eye movements differ between cross-eyed and visually-normal infants? (2) How can we alter the development of these brain circuits to prevent or cure crossed eyes in infancy? (3) Can early surgery prevent maldevelopment of these brain circuits?

   Highlights:
Our team is actively conducting a prospective clinical trial at The Hospital for Sick Children in Toronto to assess the effects of early versus standard surgery in very young children. Using motion visual evoked potentials to measure brain activity, we are one of the first to show that early surgery in human infants is superior to standard surgery in promoting brain development, and shed light on the critical periods of visual development and functional recovery in humans.

   Our team, in close collaboration with Dr. Lawrence Tychsen at Washington University in St. Louis, has pioneered the use of a non-human primate model to study crossed eyes in infancy. Our work has led to new understandings of the fundamental brain mechanisms involved in crossed eyes in infancy, and the realization that early correction is critical to prevent or cure this condition. Using an animal model:

o  We are the first team to use sophisticated recording technique to measure eye movements with precision in very young monkeys.

o   We are one of the first to demonstrate that if correction of crossed eyes is done at a very early age, we can prevent or cure the abnormal sensory and eye movement behaviours typically seen in children with crossed eyes.

o   We are one of the first to demonstrate that crossed eyes in infancy is not only an eye problem, but that it is also a brain problem as a result of abnormal wiring in the primary visual cortex.

2.Lazy Eye (Amblyopia) is a visual impairment of one or both eyes caused by inadequate use during early childhood; it cannot be corrected immediately by prescription glasses. It is the most common cause of visual impairment in one eye in the western world, and affects about 3-5% of the general population. Although tremendous amount of resources are spent on preventing and treating lazy eye, approximately 50% of children do not respond to therapies, and thus, many patients with lazy eye continue to have abnormal vision throughout their adult lives. Our goal is to understand how lazy eye affects the visual brain and to find a cure for it. Specifically, our research aims to answer four major questions: (1) How do the brain circuits in people with lazy eye differ from those with normal vision? (2) How does lazy eye affect three-dimensional (3D) depth perception and eye movements? (3) How do the eye-hand coordination skills in people with lazy eye differ from those with normal vision? (4) How can we develop more effective treatments for lazy eye?

   Highlights:

o  We are the first group to demonstrate that patients with lazy eye have impaired perception of images of real-world scenes.

o   We demonstrate that patients with lazy eye have abnormal saccades as a result of slower visual processing in the afferent (sensory) pathway, rather than a deficit in the efferent (motor) pathway of the saccadic system.

o  We demonstrate that lazy eye affects both the programming and execution of visually-guided reaching, which may reflect a strategy or adaptation of feedforward / feedback control of the visuomotor system to compensate for degraded vision in lazy eye.

3.Double Vision (Diplopia) / Strabismus from Brain Diseases is a common and disabling feature of many diseases that affect adults, including strokes, brain tumours, diabetes, and multiple sclerosis. Our goal is to understand the brain mechanisms that cause double vision and to find a cure for it. Specifically, our research aims to answer three major questions: (1) How are the three-dimensional characteristics of eye movements altered by diseases of the brain? (2) What are the mechanisms underlying these changes, and how do they adapt over time? (3) What are the effects of different kinds of surgery on vision and on brain recovery / adaptation?

   Highlights:
Our team has devoted much effort to understand the pathophysiologic mechanism underlying skew deviation, which is a vertical strabismus caused by supranuclear lesions in the brainstem or cerebellum.

o  Our work has provided the first systematic evidence that skew deviation is caused by damage of a specific brain circuit that involves the utricles in the inner ear and the ocular motor nuclei.

o  Because differentiating skew deviation from cranial fourth nerve palsy often pose a diagnostic challenge to clinicians, we devise a novel clinical bedside test to differentiate between these two conditions based on our new understanding of the pathophysiologic mechanism underlying skew deviation. This new clinical test is now being adopted and used in major centers across North America.

Additional achievements include:

o  Our modelling study on opsoclonus in 3D (involuntary chaotic eye movements commonly found in patients with tumours) has led to new discovery of a specific brain structure (fastigial nucleus of the cerebellum) that is responsible for causing it.

o  Our work on the vestibule-ocular reflex in 3D (the reflex that allows our vision to remain clear during head movements) has shown that the time-honoured Hering’s law is not immutable, and has contributed to a new understanding of how the brain controls eye movements.

o  Our study of 3D eye movements in neurologic patients has unravelled novel adaptive strategies used by the brain in the face of diseases.