The eyes have it

Eye movements have been used to gain better understanding about the functioning of the brain and now clinicians have gathered enough sophisticated information to consider eye movements as early-stage biomarkers for Parkinsonian disorders

Over the past three decades, eye movements have increasingly been applied as an experimental tool in behavioural and cognitive neuropsychological experiments. The study of eye movements is a source of valuable information to both scientists and clinicians. To the neurobiologist, the study of the control of eye movements provides a unique opportunity to understand the operation of the brain. For neurologists and ophthalmologists, abnormalities of ocular motility are frequently the clue for the localisation of an existing disease.

Since 1965, eye movements have been used to evaluate abnormalities and to link these to the diagnosis in patients with neurological disorders. More specifically, oculomotor abnormalities were described in Parkinson’s disease, as eye movement tracking was used to evaluate the effect of the treatment in such patients. Some atypical Parkinsonian syndromes without response to levodopa treatment were also clinically identified, including progressive supranuclear palsy (PSP), cortico-basal degeneration (CBD) and multi-system atrophy (MSA). Parkinsonian disorders are pathologies which present the same symptoms as the Parkinson’s disease. They are particularly difficult to diagnose, especially at the onset due to the similar symptoms. Neurologists are usually only able to give an accurate diagnosis several years after the appearance of the first symptoms.

Several studies underlined abnormal eye movements in these atypical Parkinsonian syndromes, all of which used three of the above mentioned systems (EOG, IR and SSC) to record eye movements. Some studies showed that the major criteria to help clinicians deliver the appropriate diagnosis was based on the horizontal and vertical velocity of eye movements, which could be easily obtained with the VOG method.

A research and clinical team from the French Pitié-Salpêtrière Hospital in Paris, led by Prof Marie Vidhailet, uses eye movement examination to help diagnose Parkinsonian disorders. Thanks to the recording and the analysis of eye movements, the team is able to differentiate three of the main Parkinsonian disorders: PSP, CBD and MSA. Dr Bertrand Gaymard from the Pitié-Salpêtrière Hospital reports that “the brain areas implied in eye movement are well known. If the eye movement analysis detects an abnormality, we know quite precisely which structure of the brain is responsible for the abnormality”. Since the Parkinsonian disorders involve different brain areas, it is thus possible to differentiate them by determining which parameters of eye movements are abnormal. For the clinical examination, the team uses an Eye Brain Tracker from e(ye)BRAIN, currently the only company specialised in developing a medical device for the clinical evaluation of eye movement. The Eye Brain Tracker was specifically developed in collaboration with the team of the Pitié-Salpêtrière hospital.

The eye movement examination involves the display of visual stimulations on a computer screen and the recording of eye movements, followed by their analysis.

One of the tests is called ‘gap’. It involves the display of a fixation cross in the centre of the screen for 2500 to 3500ms, and then removing the fixation cross for a time gap of 200ms, followed by the appearance of the target on the right or on the left of the screen for 1000ms. This sequence is repeated for one minute, and patients have to look at the fixation cross and the target when it appears.

The test allows the examination of reflexive saccades, which are rapid eye movements shifting the line of sight between successive points of fixation. Different parameters of the saccades are automatically extracted and compared to normal values. One of these parameters is the reaction time (latency), which is the interval between the appearance of the target and the time when saccades start; while others include the saccadic velocity or the saccadic trajectory.

A second test is the so-called ‘up down test’, where the fixation cross is presented again for 2500 to 3500ms. After that the fixation cross is removed and a target is presented for 1000ms above or below the preceding position, without a “time gap”. This sequence is then repeated for one minute. The patient has to look at the fixation cross and the target when they appear. Measured parameters are the same as in the case of the gap test.

A third type of examination is the ‘antisaccades test’. This allows the investigation of the control of voluntary saccades. Patients are required to suppress a saccade (the “prosaccade”) toward a stimulus that appears in the periphery of the vision, and asked to generate a voluntary saccade of equal size to the opposite side (the “antisaccade”) instead. Again, the stimuli displayed are the same as during the gap test, while the analysed parameters include the number of errors as well as latency.

In a further test, called ‘pursuit’, a target is moving either horizontally or vertically, which the patients should follow. Here, examiners analyse the presence of jerks at the eye movements.

Thus, during eye tracking experiments, various parameters are evaluated – including reaction time, eye movement velocity, eye trajectory, and the accuracy of the gaze – besides cognitive functions like preparation, activation or inhibition of the movement. The recording of eye movements is a very high-performance tool, while it’s non-invasive, safe, quick and provides objective results even with patients at later stages of diseases.

“Recordings of eye movements in patients with Parkinsonian syndromes have become necessary to help with the diagnosis at the onset of the pathology. In general, several abnormalities in eye velocity and in cognitive functions are found. VOG systems with a high frame rate (over 300Hz) are very safe and paradigms testing activation inhibition and smooth pursuit are very useful for neurologists,” summarises Dr Sophie Rivaud-Pêchoux, from the Pitié-Salpêtrière team.

Results are so promising for the diagnosis of Parkinsonian disorders that e(ye)BRAIN now conducts clinical studies on multiple sclerosis, in order to check the ability of eye movement tracking in the diagnosing of this pathology as well.