Fondation Ophtalmologique Adolphe de Rothschild

Homonymous lateral hemianopia (HLH) is characterized by loss of vision in half the visual field, and is the most common neurovisual disorder following stroke.
Numerous behavioral and neuroanatomical studies have focused on the phenomenon of blindsight, corresponding to patients' unconscious residual visual capacities in the blind hemifield. Cohort studies of patients have highlighted different types of blindsight, and a low occurrence of the phenomenon initially described: (1) type 1 blindsight (≈12%), unconscious visual abilities; (2) type 2 blindsight, visual abilities associated with sensations in the blind field (≈18%); (3) blindsense, sensations in the blind field without visual abilities (≈30%); and (4) no blindsight (≈40%). The heterogeneity of these blindsight abilities in the HLH population is closely related to patients' neuroanatomical and functional profiles.
In particular, resting-state functional imaging (r-fMRI) and default mode network analysis have highlighted a significant correlation between the degree of inter-hemispheric connection (between the healthy and injured hemispheres) and the rate of spontaneous visual field recovery. To our knowledge, this degree of functional connectivity has not yet been studied in relation to blindsight abilities. However, this functional MRI measurement tool represents a potential predictive factor for patients' residual performance in their blindsight field, in order to assess the level of visuo-cognitive impairment and, ultimately, to adapt care.

Alzheimer's disease (AD) is a clinico-pathological entity combining multiple and varied neuropathological lesions with characteristic abnormal accumulations (amyloid Beta (Aβ) plaques and neurofibrillary degeneration (NFD)), neuroinflammation, as well as neuronal and synaptic suffering.
To date, only symptomatic treatments are available, with no proven effect on neuropathological lesions or on the clinical course of the disease.
Anti-TNF alpha could be a therapeutic agent of choice in the treatment of central nervous sytem (CNS) diseases with an inflammatory component, such as AD. Unfortunately, their high molecular weight prevents them from passively crossing the blood brain barrier (BBB). In a pilot study published in 2006, etanercept was administered intrathecally to AD patients with encouraging clinical effects.
Transient opening of the tight junctions between the endothelial cells of the BBB by delivering High Intensity Focalised Ultrasounds (HIFU) in combination with an intravenous injection of microbubbles is a strategy that could improve bioavailability. Studies suggest that the oscillation of microbubbles in the ultrasound field generates microcurrents that induce shear forces responsible for a transient opening of the BBB. Ultrasound can be focused or unfocused and open the BBB diffusely or selectively over defined regions of the brain. This technique was first used to open the BBB in humans in 2001.
Transient opening of the BBB is also thought to modulate the immune response in the CNS, leading to a reduction in the intracerebral load of Aβ. In an Alzheimer's mouse model, several studies using ultrasound devices to open the BBB have shown a reduction in the intracerebral load of Aβ (up to 75%) and an improvement in the memory faculties and cognitive performance of the animals.
In humans, two clinical trials have assessed the safety of using ultrasound-assisted BBB disruption devices in AD patients. These were the Sonocloud® (Carthera) and ExAblate® (InSightec) devices. The Sonocloud® device is an extra-dural ultrasound emitter implanted under local anaesthetic. Enrolment was completed in October 2020, but the results of the trial are not yet available (NCT03119961). The phase I study on 5 patients evaluating the ExAblate® device coupled with the injection of gas microbubbles demonstrated reversible opening of the BBB with no serious adverse effects for the patients. No effect on intracerebral Aβ load or cognitive or behavioural improvement was demonstrated. The ExAblate® device is not implantable and is therefore less invasive than the Sonocloud® device. However, it requires MRI monitoring and the transducers used often generate high levels of heat, requiring the use of a water cooling system to avoid the risk of transducer deterioration.
In this project, our aim is to assess the safety of using a non-focused ultrasound device, the General Electric VIVID S70 clinical device (CE mark G1 023782 0112 ), to perform BBB ruptures in patients suffering from AD, combined with the administration of etanercept, whose bioavailability would thus be improved.

Many retinal pathologies are of vascular origin. In order to better understand their pathophysiology and make an accurate diagnosis, it is essential to visualise and quantify blood flow. The holographic Doppler laser (LDH) is a new medical device currently being developed by physics researchers at the Institut Langevin. The 1st prototype of this device is currently being used as part of research involving humans with minimal risks and constraints at the Hôpital National de la Vision des Quinze-Vingts (NCT04129021).
In order to better visualise, understand and quantify the vascular anomalies suspected in the fundus of patients undergoing ophthalmology treatment , we would like to acquire images/videos with a 2nd LDH prototype, within the ophthalmology clinical investigation platform at the Hôpital Fondation Adolphe de Rothschild.