Neuroophthalmology

Research of the unit neuroophthalmology centres around four clusters: i) binocularity ii) neuropeptides and proteomics  iii) multiple sclerosis iv) population screening

i) Binocularity

Development of an eyetracker that combines measurement of stereopsis and visual acuity in preverbal children.

Investigator: Dr Anne Cees Houtman (PhD student)
Promotor: Prof. dr. Marcel ten Tusscher

Infantile esotropia (IE) is a distinct clinical entity in the field of strabismus. Its onset is typically between 3 and 5 months of age. IE is incompatible with normal binocular vision because the visual axes are not aligned. There is no correlation between the (monocular) visual signals from the eyes in the visual cortex. Therefore patients do not develop stereopsis (or “3D vision”). IE can delay the development of visuomotor skills, it has an impact on psychosocial development and professional requirements may hamper a patient’s career ambitions.
Stereopsis emerges around the age of 10-12 weeks of age in normal infants and can be demonstrated by so-called Forced Choice Preferential Looking (FCPL) assessment in 60% of children around that age. Interestingly this can also be demonstrated in 60% of infants who will later develop IE. The majority of the latter subsequently lose their stereopsis. 
There is a controversy regarding the timing of surgical treatment of IE, i.e. early or late. Theoretically it makes sense to offer very early surgery (to realign the visual axes)  to those infants who have demonstrable stereopsis but testing for stereopsis in preverbal children is cumbersome and practically never used in a clinical setting.
 The Stereotracker combines an autostereoscopic screen and an eye-tracker to make an automated FCPL assessment of stereopsis or visual acuity in preverbal children . The Stereotracker should ultimately help in identifying those patients that will benefit from (very) early treatment. But it may also be a vision screening tool by combining tests for visual acuity and stereopsis.
A prototype of the Stereotracker has been developed in the first stage of this project. Preliminary studies have indicated that the concept of the Stereotracker is valid but refinements will need to be made before the device can be put to a clinical test. Currently the performance of the eye tracker appears sufficient to test adults but not preverbal children. Solutions may be found in improving the software component or replacing the eye tracker by a more robust system.


The origin of strabismus

Investigator: Prof. dr. M ten Tusscher

The sensory cause and motor aspects of infantile strabismus, fusion and binocularity are studied with functional MRI.
A closer look at the evolution of the eye and the brain provides a possible explanation for both the origin of infantile esotropia and its motor characteristics. In the course of evolution the eyes have moved from a lateral to a frontal position. Consequently the monocular visual fields started to overlap resulting in a binocular visual field. In lateral-eyed animals the retinae project to the contralateral visual cortices only. These projections are also found in binocular mammals and birds with binocular visual fields but in addition there are uncrossed projections from the temporal retinae to the visual cortex. The partial chiasmal decussation and the corpus callosum provide the necessary structure that allows binocular vision to develop.
Disruption of normal binocular development causes a loss of binocularity in the primary visual cortex and beyond. Beyond the primary visual cortex the contralateral eye dominates while the temporal retinal signal appears to lose influence. Loss or absence of binocular vision in infantile esotropia may be caused by inadequate retinotopic matching between the nasal and temporal retinal signals like in albinism with an abnormal or asymmetric chiasmal decussation, or agenesis of the corpus callosum.
Dominance of the crossing retinal signal might also explain the motor characteristics of infantile esotropia (asymmetric OKN, latent nystagmus, DVD). A normal binocular cortical signal will predominate over the evolutionary older, originally non-binocular, retinal projections to the superior colliculi (CS) and the accessory optic system (AOS). A suppressed temporal retinal signal paves the way for the re-emergence of eye movements driven by one eye, as in lateral eyed non-binocular animals.

ii) Neuropeptides and proteomics

Investigator: Dr. Peter Raus (PhD student)
Shared promotorship: Prof. dr. P Verhaert, Delft technical university/ Prof. dr. M ten Tusscher

There are an estimated 285 million people with visual impairment worldwide, of whom 39 million are blind. The pathogenesis of many eye diseases remains poorly understood. Proteomics  may provide key insight into the biological pathways of disease. We try  to identify new biomarkers for eye diseases using proteomics. Recent advances in proteomics now allow the identification of hundreds of proteins in eye fluids. The large repertoire of investigative proteomic tools has great potential to transform vision science and enhance understanding of physiology and disease processes that affect sight.
Dr Raus is interested in Sjogren syndrome en dry eye pathology. He investigates tear fluid peptides in order to find biomarkers for Sjogrens disease and diagnose and possibly treat dry eye disease.
Together with the diabetes department of the VUB eye fluids of patients will be investigated in order to try and find biomarkers for ischemic  diabetic ocular disease.
In another arm the effect of refractive corneal surgery on neuropeptides secretion will be studied.


iii) Multiple sclerosis

Investigator: Dr. Michel van Lint (PhD student)
Promotor: Prof. dr.  M. ten Tusscher

The retina is the most approachable part of the brain. Recent studies of the retina in patients with multiple sclerosis (MS) demonstrated neuronal and axonal loss besides macular oedema. The human retina promises to be a window into the health of a patient with multiple sclerosis.  A clear view of the retina in-vivo, with high resolution detail, could give the vital detail that may enable clinicians to make early and accurate diagnosis of the disease and possibly shed light on its aetiology which until now remains elusive. Neuronal loss in MS can be severe and occurs throughout the brain and is already demonstrated in patients presenting with their first clinical attack of MS. This reduction is still present one year later and was independent of whether the patients had progressed to develop MS. MS patients demonstrated an average of 46 per cent faster thinning of the ganglion cell nerve layers in their retinas compared to the healthy patients. These data suggest that quantification of axonal thickness in the retina by optical coherence tomography provides concurrent information about MRI brain abnormality in MS. In addition macular microcystic edema in MS patients was described recently.
Adaptive optics with optical coherence tomography and confocal microscopy allows retinal analysis at the molecular level. The present study may help in identifying those patients that will develop multiple sclerosis or benefit from early treatment.


iv) Population screening

Investigator: Dr. Zahra Javdani
Promotor: Prof. dr. M. ten Tusscher

Preventable and treatable eye diseases are found to occur very often in the elderly. Often the individual with such a disease is unaware of it. A population study will be undertaken to quantify the incidence of unknown ocular pathology and low vision. Another objective of this study will be a comparison between a questionnaire with some simple tests and high-tech imaging devices.

 

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