Patent Application
20240164671
The present invention operates in the field of systems for the diagnosis of neurodegenerative pathologies and, in particular, is based on eye-tracking technology and, more particularly, on the analysis of gaze movements and latencies.
Neurodegenerative diseases such as Alzheimer's, Parkinson's, multiple sclerosis etc. have, from the clinical standpoint, a variety of symptoms that characterize the different pathologies and the progression of the degenerative processes.
Among the symptoms taken under consideration, the visual function is often overlooked. The retina, nervous component of the eye bulb is effectively part of the central nervous system and cannot be extraneous to the above-indicated degenerative processes. Experimental results, especially in animal models and observations in patients, have confirmed this hypothesis.
Recently, there has been increased attention on the visual function and on the deterioration thereof for two reasons: firstly, since sight is fundamental for maintaining a good quality of life in patients, particularly in Parkinson's and in sclerosis where the motor activity is compromised and a correct time-space evaluation of the surrounding environment can be fundamental for preventing collateral damage such as falls or other. Secondly, since the access to the visual function is relatively simple and it could become an early diagnostic system for the pathological process, and be practical for monitoring the effectiveness of therapeutic treatments.
In order to reach these two objectives in the present invention, a system is described for carrying out a simple diagnostic test, capable of measuring, in a quantitative manner, perceptive thresholds, latencies, response amplitudes and easily measurable functional deficits, like visual-motor coordination (saccades tied to perceptive thresholds), easy-to-use even for the general practitioner and, above all, low cost for a widespread use through the territory. For this purpose, the system described hereinbelow is capable both of generating visual stimuli that is quantitatively characterized, and of recording the visual and motor responses in an accurate manner.
At the present state of the art, there are many devices that carry out eye movement analysis, usually intended for a generic use, which must therefore be integrated in an ad hoc system in order to perform the requested functions. In the medical field, the most frequent applications regard the use for surgical purposes or the use for treating the visual apparatus itself.
The objective of the present invention is instead that of creating a device with a very well identified purpose, dedicated for a very specific task, for which the devices present on the market have characteristics that are not entirely adherent to the needs set forth hereinbelow. In the patent CA2827498A1, a method is published for the differential diagnosis between Parkinson's disease and progressive supranuclear paralysis. Nevertheless, the patent explicitly states that any one eye-tracking system is usable for this type of application, recommending a sampling frequency of the movement of at least 500 Hz. In order to be able to extend the diagnosis to other types of degenerative diseases, it is however necessary to account for the sensitivity to brightness, a problem not confronted in this patent but brilliantly resolved in the invention described hereinbelow.
The attention to the brightness is not even considered in the patents US2016106315A1 and US2014221869A1, in which eye-tracking solutions are proposed for the diagnosis of neurological diseases, which are nevertheless simplified and do not account for the interference of the environmental light in the precision of the diagnosis of specific pathologies, which can instead be covered due to the present invention.
There is no doubt, therefore, that such solutions only partly confront the critical items described above.
According to the present invention, an interactive gaze analysis kit is attained for the early diagnosis of neurodegenerative pathologies which effectively resolves the abovementioned problems. The central nervous system and the eye are deeply connected both functionally and physiologically. The bond between these two structures starts during the embryonic formation, when the optical vesicle is formed from the embryonic layer assigned to form the nervous system. The visual pathways are constituted by photoreceptors which transduce the captured light impulse into nervous impulse that will then be sent from the nervous retinal cells, which constitute the optical nerve, to the visual cortex of the brain. Clinical and basic research show that there are neurodegenerative diseases and pathologies that affect the central nervous system which show particular alterations at the eye. For example, in Alzheimer's disease, characterized by the depletion of neurons at the cerebral cortex which determines alterations of the memory, dysfunctions of language and of perception, the patients affected by this pathology experience alterations of the visual field, reduction of the sensitivity to contrast, perception of movement, altered viewing of colors and alterations of the oculomotor function. Also in Parkinson's disease, caused by the loss of dopaminergic neurons of the brainstem, there is a clear effect on the vision. Indeed, dopamine is an important neurotransmitter even at the retina, dopaminergic cells are present in the inner plexiform of the eye and receptors for dopamine were identified on the cells of the retinal pigment epithelium, on the photoreceptors, and on the ganglia cells. The dopamine modulates the receptor fields of the retinal cells in order to ensure sensitivity to contrast, vision of the colors and it has a role in adaptation to light. At the eye, the patients affected by Parkinson's disease can experience defects of convergence and reduction of visual acuity. Multiple sclerosis, another neurodegenerative disease, is characterized by a demyelination of the axons. Optic neuritis is the first clinical manifestation of the disease in about 20% of the patients and 75% of the patients affected by the sclerosis have had at least one episode during their lifetime. The visual symptoms are the result of the demyelination of the visual pathways and the consequent optic neuritis appears with monolateral reduction of the visual acuity, of the color vision and of the sensitivity to contrast and with alteration of the visual field. The existence of these eye alterations, in many neurodegenerative pathologies, confirmed in various studies and various authors, underlines the strong bond between the eye and Central Nervous System (CNS). In many cases, the eye manifestations precede the central symptoms, suggesting that the eye imaging can be a valid aid in the early diagnosis of these diseases. From many aspects, the eye is a privileged site for research since the eye structures are easily accessible from outside and it is possible to examine them in vivo without any risk for the patient. Presently there are many diagnostic devices which analyze the eye movement and, generally, visual perception, but most of these are limited to the functional analysis of the eye, not including a diagnostic connection with other pathologies of neurodegenerative type.
The present invention instead has the object of creating a device which allows, through an integrated analysis of the visual perception, monitoring and measuring a series of parameters, an early diagnosis of several neurodegenerative diseases, like those mentioned above. In order to effectively describe the characteristics of the device of the present patent, it is useful to underline the difference between eye tracking and gaze analysis, the first is involved with measuring the eye rotations with respect to a reference, such as the head of the subject, while the second analyzes the point actually looked at within the scene. While the diagnostic systems presently on the market are directed towards gaze tracking, the present system instead focuses on the analysis of the eye movement of the patient, while he/she is asked to look at a specific point in space and at the same time stimulated by means of specific and localized light stresses. With this simplification, one knows ahead of time the direction and the distance of the point to be observed and hence it is not necessary to calculate it; indeed the direction of the gaze is not the first objected to be attained, but in the end the information of interest is contained in the capacity of the eye movement of the patient when it is stressed by light stimuli or the point to be observed is moved. The interactive present system of gaze analysis carries out an analysis and a monitoring of the eye movement of a patient by underlining, by means of a compared analysis and a calculation of pre-established parameters, the presence of behaviors of the visual apparatus which signal the possible presence of neurological pathologies. The system is constituted by a video camera which carries out a filming with a spatial and temporal resolution of the eyes of the patient sufficient for meeting the relative accuracy requirements. The camera, for example comprising a charge-coupled device (CCD), may be suitable for use in the visible spectrum, or with infrared wavelengths of light, or with visible spectrum and infrared wavelengths. The filming is carried out in complete darkness and while the patient directs his/her gaze towards a suitable screen i.e. display which shows the test images which stimulate the eye movement. For the diagnostic test to which the patient is subjected, it is necessary to have an appropriate screen e.g., an LCD screen e.g. with LED backlighting. A further linear polarizing filter may optionally be added, in frontal position, at the end of the light path. Ideally the luminance of the screen should be as low as possible. Such further linear polarizing filter modulates the quantity of light exiting from the screen, thus to modify the luminance thereof, lowering it, so as to eliminate all the reflections from the image of the eyes which is registered by the video camera. The polarized filter can be held fixed or rotated by means of an electronic actuator connected to the software equipping the present system, so to analogically modify the effect. In order to ensure a complete darkness during the analysis, the present system is provided with a dark tunnel or box which prevents the passage i.e ingress of external light. The patient looks at the screen through the tunnel or box, e.g. made of fabric or rigid material with an opening at the patient side end so as to allow him/her to position the face with the gaze directed towards the interior of the tunnel or box, in any case without penetrating the external opening. The patient side of the screen, integral with the vision system and with the dark tunnel, is mounted on a vertical axis translating in a manner such that it is possible to adjust the height of the abutment and be adapted to the various situations of patients and abutment planes with different heights. This end, in order to ensure health safety, can also have an automatic sterilization system based on emission of UV rays. In the tunnel embodiment, on the side opposite the opening for the face of the patient, another opening is made that is suitable for housing the screen directed towards the face of the patient. In the box embodiment, the box comprises (i.e. contains in its interior) the screen directed towards the face of the patient. Since the patient will be requested to operate in conditions of darkness, in order to illuminate the scene (i.e. particularly the face and especially the eyes of the patient), necessary for the filming of the video camera, an infrared lighting system will be employed e.g. by means of a system of one or more infrared LED illuminators with an emission frequency such that they are not visible; and optionally a filter for screening the visible light, thus ensuring the best performance. In an alternative embodiment, the lighting system is able to illuminate in infrared and the visible spectrum, for example via one or more types of illuminator for example covering all or parts of the infrared and visible spectral range. With such an arrangement, a patient may be first tested using visible spectrum illumination to acquire a first degree of information about the patient, for example the detection of some delay in ocular motor responses. Patients exhibiting such responses can then be subjected to a second level of analysis using infrared illumination to further characterize the deficit of the patient. In this embodiment, the video camera may optionally have a filter that is adapted to screen (i.e. remove) the visible light when infrared illumination is used. When a test is performed using visible spectrum illumination, optionally a range of luminance simulating the range from dusk until dawn is used. The position of the patient is provided with an input peripheral device e.g. comprising two buttons placed laterally with respect to the structure of the tunnel or box, one per hand. All the tests were designed for being executed with this extremely simple interface, such that they can be performed even by elderly patients. The device guides the patient in the test with instructions on the video and audio messages that ask the patient to respond, for example, to simple questions on the images shown by indicating, by means of the buttons, the selection that best approaches one's own visual perception. The physician, however, interacts with the device by means of a touchscreen display and a physical keyboard that allows the management of the tests and the display of the results and of the movement of the eyes of the patient to be examined, recorded by the video camera in real time. The device provides for various analysis modes, such as for example the display of micronystagmus, i.e. the display of a single image of a few strongly contrasted pixels and the amplitude and speed measurement during their fixing; or the analysis of the reflected saccades, i.e. the display of a small image with an instantaneous movement for measuring the amplitudes and the speeds with which a patient reacts. Once the data regarding the functioning of the visual apparatus has been acquired, due to the filming and recording of the video camera, this may be inserted in a calculation system that will perform all the computation functions regarding the collection and the analysis of the observed data. The software with which the present device is equipped is suitably able to process the set of input data such to detect the presence of micronystagmus, the reaction times following optical stimulations and to measure the light sensitivity threshold, which overall, subject to a specialist medical anamnesis, can allow an early diagnosis of a plurality of neurodegenerative pathologies. It is also possible to configure the device in a manner such that it subjects the patient to automatically preset tests, by means of, for example, the use of earphones through which the user can listen to the pre-recorded instructions of the tests, thus allowing a single doctor to coordinate research on multiple patients simultaneously, by means of the use of multiple devices. The components of such device have reduced dimensions and are highly modular so to facilitate the use and transport. Materially the device may appear as a suitcase that allows two mechanical configurations: one for transport and one for use, and during the latter the two halves of the “suitcase” are open at 180° and being aligned form the abutment base of the device itself. Also, the power supply of all the components of the system may be designed so to facilitate the use of the device; indeed it may be constituted by a battery in a manner such that the apparatus can be used free of constraints tied to the fixed power grid. In order to make the performance of the test more comfortable, the present system can be provided with an additional instrumentation for the environments where the test is performed. Since the patient must complete the test in complete darkness, at its conclusion, when he/she moves his/her face away from the dark tunnel or box, the patient might be uncomfortable or even undergo a light shock when exposed to the external light. In order to overcome this drawback, a suffused red-light lighting system can be installed in the environment where the test is performed so as to not create an excessive difference between the night vision of the patient during the test and the vision of the surrounding environment at the end of the test.
The advantages offered by the present invention are evident in light of the description set forth up to now, and will be even clearer due to the enclosed figures and to the relative detailed description.
The invention will be described hereinbelow in at least a preferred embodiment by way of a non-limiting example with the aid of the enclosed figures, in which:
The present invention will now be illustrated as a non-limiting or non-binding example with reference to the figures, which illustrate several embodiments relative to the present inventive concept.
With reference to
An interactive gaze analysis kit as described herein may be used for the early diagnosis of neurodegenerative pathologies and is adapted to allow an analysis and a monitoring of the eye movement of a patient, calculating the presence of behaviors of the visual apparatus which signal the possible presence of neurological pathologies.
Finally, it is clear that modifications, additions or variants that are obvious for a person skilled in the art can be made to the invention described up to now, without departing from the protective scope that is provided with the enclosed claims.
The invention may also be embodied by the following clauses:
| Number | Date | Country | Kind |
|---|---|---|---|
| 102021000007313 | Mar 2021 | IT | national |
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/IB2022/052750 | 3/25/2022 | WO |
