Patent Publication Number: US-2010118264-A1

Title: System and Methods for the Treatment of Retinal Diseases

Description:
CROSS REFERENCE TO RELATED APPLICATIONS 
     This application is a continuation of U.S. patent application Ser. No. 11/343,960, filed Jan. 31, 2006, which is a continuation-in-part of U.S. patent application Ser. No. 10/503,869, filed May 18, 2005 in the United States claiming priority from PCT Patent Application No. PCT/EP02/01339, which was filed in English on Feb. 8, 2002, all of which are hereby incorporated by reference herein in their entirety. 
    
    
     TECHNICAL FIELD AND BACKGROUND ART 
     The present invention relates to the treatment of retinal diseases, and in particular, to the treatment of retinal diseases using vision restoration therapy (VRT). 
     Damage to the visual system, as used herein, is defined as impairment of any structure (or of all structures) involved in the processing of vision. These structures include, but are not restricted to, the nervous system tissue from the level of the retina, including the retina up to the optic nerve and all brain structures involved in process of vision. Such damage leads to visual deficits or even a loss of visual functions which may lead to partial or more or less complete blindness. This damage may come from many sources and may include damage to the retina. Damage to the retina may be caused by various diseases including, but not limited to, retinal diseases such as glaucoma, age related macula degeneration, or retinitis pigmentosa. The retina may also be damaged by retinal detachment or laser damage. In addition, the retinal may become or originate damaged based on inflammation, inherited genetic defects, metabolic issues or other causes. Damage to the retina shall be referred to herein as “retinopathies.” 
     Retinopathies in general have not been deemed amenable to reversal using the inherent plasticity of the central nervous system (CNS), and only surgical or pharmacological interventions have been considered. That is, damage to the retina, either by disease or other means, typically requires surgery for the patient to have any restoration of vision that may have been lost. 
     SUMMARY OF THE INVENTION 
     Embodiments of the present invention may utilize a behavioral training of patients, such as a VRT, to treat damage to the retina and restore at least some (if not all) of a patient&#39;s vision. This may be accomplished by presenting visual stimuli on a simple device for emitting optical stimuli to the visual system of a human in such a way that target stimuli may be presented to various zones of the visual field: the intact sector of the visual field, to partly damages zones, or to blind regions, or all of them. Clinical tests suggest that treatment as described below may improve the vision of patients having retinal damage. 
     In one embodiment there is provided a method for treating a retinal disease in a human. The method of this embodiment may include locating and defining one or more zones of vision within the human&#39;s visual system and defining a treatment area which is located within at least one of the zones. The method of this embodiment may also include treating the human&#39;s retinal disease by presenting visual stimuli to the treatment area at a specified location and with a specified definition and recording changes in specified characteristics of the human&#39;s visual system. This method may also include reiterating the previous steps so as to improve the human&#39;s overall visual system. 
     In another embodiment there is provided a device for treating a retinal disease in a human. In this embodiment the device may include at least one optical stimuli presenting means and a fixation point means allowing the fixation of the human&#39;s view. The device of this embodiment may also include means for entering the human&#39;s response to optical stimuli perceived and means for allowing a control of the at least one optical stimuli presenting means in accordance with the performance of the human responding on optical stimuli perceived. The device of this embodiment may also include a central data processing means for recording, storing, processing and emitting data from the optical stimuli presenting means, the fixation point means, the means for entering the human&#39;s response, and the means for allowing a control of said at least one optical stimuli presenting means. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       The foregoing features of the invention will be more readily understood by reference to the following detailed description, taken with reference to the accompanying drawings, in which: 
         FIG. 1  represents vision in a normal visual field; 
         FIG. 2  represents a visual field where one hemisphere does not function; 
         FIG. 3  represents a visual field where the central area of the visual field is injured; 
         FIG. 4  shows the presentation of two stimuli in sequence; and 
         FIG. 5  shows another presentation of two stimuli in sequence. 
     
    
    
     DETAILED DESCRIPTION OF SPECIFIC EMBODIMENTS 
     The invention relates, generally, to a process for treating retinal diseases in a human by presenting optical stimuli to the human. The stimuli may be presented to either a zone within the intact visual field of the person or a zone outside the intact visual field of the human, or both. One of these zones is a zone to be treated, thereby allowing an improvement of the vision in general. 
     One feature of the present invention is that the treatment by stimulus presentation may predominantly occur in or near the zone of intact vision, but optionally also in the zone of deteriorated vision or in the zone of residual visual function or in the zone of partial visual system injury, i.e. in the transition zone. Yet another alternative would be to treat the blind region or a combination of all zones. The treatment, by presenting visual stimuli, occurs preferably only in the zone of intact vision, although a parallel or consecutive presentation of optical stimuli to at least one other zone, e.g. to the so-called “transition zone” or the blind field may occur, in addition to the presentation of stimuli to the zone of intact vision. In other embodiments, visual stimuli may only be presented to the zone outside the intact visual field. 
     The term “zone of intact vision” as used herein means the zone of the visual field (or brain area) which is substantially not injured or influenced by the events resulting into an impairment of the visual system, i.e. shows more or less normal visual performance when receiving optical stimuli. In contrast, the term “zone of deteriorated vision” (which is used in a similar sense as the term “zone of residual visual function” or the term “zone of partial visual system injury”) is defined to mean the zone where events like accidents, stroke, degenerative diseases, or retinal diseases such as glaucoma or retinitis pigmentosa caused damages of the brain regions or the retina influencing the visual capabilities of the human so that the vision is at least partly deteriorated or even partly or completely lost. The term “blind zone” is meant to indicate those regions where a patient does not respond to stimuli at all. 
     Zones of intact vision, on the one hand, and zones of deteriorated or even lost vision (“blindness”), on the other hand, may be shaped continuously, i.e. as zones of a certain (e.g. round) shape, wherein the zone of said shape has more or less identical visual capabilities, as, for example intact visual capabilities. Such continuous zones may be adjacent to another (optionally similarly shaped) zone having a different visual capability as, for example, a zone of deteriorated vision, which, in turn, may be followed by a zone where the vision was completely lost. However, it may also be possible that several zones of intact vision are surrounded, in a discontinuous manner, by zones of deteriorated or lost vision. When the visual field is lost, for example, following glaucoma, a typical regional field loss (scotoma) occurs. Often, the person having experienced said event can still fixate, and the region of intact vision is in one specific area of the visual field. In the case of macula degeneration diseases or other diseases that lead to a loss of fixation ability due to loss of the function of the fovea, there may be a circular visual field that is donut-shaped, with a deficit region in the centre of the visual field (damaging the fovea) and with intact (or partially damaged) areas surrounding it (see  FIG. 3 ). 
     In another embodiment the zones of intact vision are located, defined and characterized, instead of (or optionally together with) zones of impaired, i.e. deteriorated vision or residual visual function or partial visual system injury. The zones of deteriorated vision or impaired vision or partial visual system injury are hereinafter shortly referred to as “transition zones” (see  FIG. 2 ), while the zones of intact vision are simply referred to as “zones of intact vision”. Such transition zones may, for example, be found with aged people whose vision, for example peripheral vision, becomes more and more restricted. Transition zones may also be found with people whose visual system was influenced as a result of a brain injury, stroke or similar event. Another example are transition zones between zones of completely maintained and wholly lost ability to visually discriminate between colours, shapes or movements. However, in one embodiment the predominant treatment areas or treatment zones may be located in the intact vision zones. 
     In one embodiment, the size and location of the treatment area or areas within the intact vision zone(s) may be selected in accordance with the size, location and kind of the zone of partial visual system deterioration, of residual visual function or visual deficit of the human. In other words, it may be beneficial to check which parts of the visual system of said human offer the greatest chance for improving the overall vision by the subsequent treatment by presenting optical stimuli. In one embodiment the transition zones may be treated together with the zones of intact vision. 
     Based on the individual person&#39;s performance, which may be determined continuously or intermittently during the treatment, treatment stimuli may be presented in those zones of intact vision. The type, shape, intensity, duration and time sequence of the treatment stimuli is not restricted; there may be used one type of treatment stimuli or several types of treatment stimuli. In the latter case, several types may be used simultaneously or in a time sequence. In some embodiments of the invention, optical or light stimuli are presented to the person&#39;s visual system. In some embodiments the light stimuli of different colour, luminance, intensity and/or shape may be presented to the visual system of the person being treated. Such light stimuli can be presented as static light stimuli or a series of light stimuli in a sequence generating an impression of a moving object. In another embodiment, stimuli in the form of simple or more differentiated pictures of articles of daily life may be presented to the intact vision zone of the person to be treated. Such pictures may be static or moving (dynamic), according to the needs. In one embodiment of the invention optical stimuli are presented to the intact vision zone of the person to be treated, which have the form of letters, ciphers or even words or sentences. The invention, however, is not at all restricted to the above preferred embodiments of stimuli to be presented. 
     In a first process step, the person&#39;s visual field defect is measured. This includes the step of establishing a zone of intact visual field. The measurement is done by methods which are, as such, known from the prior art. In one embodiment of the invention, standard perimetry devices may be used, i.e. those devices, which are commonly used in the opthalmological practice. In a preferred embodiment of the invention, a computer-based campimetric measurement is conducted. With such a device, blind, partially injured and intact sectors of the visual field can be defined. 
     The definition of what comprises the border between the intact zone and the partially injured zone or the intact zone and the blind zone may vary. Its position will depend on what kind of stimuli are used to define the visual function, i.e. large or small stimuli, bright or less bright stimuli, etc., the nature of the background, i.e. cluttered or simple backgrounds, and/or the timing of the stimulus, i.e. short or long presentation times. 
     In the second step, the zone or area of intact vision is defined, based on the measurement of the first step. The definition of the intact visual field depends on the nature of the visual stimulation selected for said definition. Stimuli which are seen more easily by the person to be treated will produce a larger apparent visual field, while stimuli which are responded to less will produce smaller apparent visual fields. Whatever method is selected to define the visual field or intact visual zone, the result of this step is a clear zone or area of vision that is defined to be intact. The shape of the intact visual field is not restricted. It may be one large area, usually round in shape, but may also consist of several intact regions which are not connected to each other. 
     In the third treatment step, a sequence of visual stimuli is presented to the intact visual zone of the person to be treated. The task the person to be treated has to perform is to respond, as in the prior art, to the stimulus presentation by a reaction which may be a step of pressing a key or any other input device in order to demonstrate that the stimulus—or a sequence of stimuli—was seen and recognized. 
     One embodiment of the present invention includes the presentation of the target stimulus to the intact vision zone(s) of the person to be treated, whereby the stimulus is selected from a library of visual objects exemplified above. The transition zone(s), near the border of blindness, may be treated in addition consecutively or may be treated in parallel. The same applies to the blind zones, which can also be selected and stimulated by presenting visual stimuli. 
     As the size and shape and optionally also the number of the intact vision zones may vary, the presentation of the stimuli is adjusted in such a way that the location and size of the objects fits within the boundaries of the intact vision zone(s) according to the above measurements. Of course, the “intact regions” used in this example embodiment disclosed herein could be replaced with transition zones on the blind zones. That is, the transition zones or the blind zones could be the zones being treated. 
     The target stimulus may be presented, for example, on a computer monitor. It could be any type of a single stimulus, or there may be selected several or many stimuli together or successively with or without different types of background. For example, useful target stimuli could be letters, words, sentences, meaningful objects (drawings, faces, photographs etc.) or objects without meaning (dots, a line pattern etc.) moving or not moving on the screen. As long as the presentation is occurring in the intact vision zone, defined as the position of the field in relation to a fixation point, and as long as the blind zone of the visual field of the person to be treated is not stimulated, any stimulus or combination of stimuli may be used. 
     By presenting the stimuli in the above-described way to the intact vision zone of the person to be treated, the intact vision zone is treated, and the treatment steps are repeated for treatment purposes. 
     In some embodiments algorithms may be used to follow the above presentation strategy, which algorithms allow the highly efficient treatment of zones or areas of visual system function (and, optionally, also dysfunction or malfunction in parallel or consecutively) and blind regions as well. The detailed steps of the treatment procedure are described below with respect to stimulating specific areas or zones of the human visual system by optical stimuli. 
     During the treatment step, changes in the characteristics of the visual system of the human treated are recorded. In other words: The performance of the person treated in view of visually recognizing the optical stimuli presented and himself/herself presenting the desired reaction on said visual recognition step is recorded by the system/device of the present invention. To give just one example: The reaction time of the treated person on an optical stimulus presented to the intact zone of his/her visual system is measured, and the time elapsed between the emission of the optical stimulus and the reaction given (for example by pressing a button of the device), relative to an average time value measured before for the treated person as a base line value, is taken as the performance of the person with respect to the treated area of the intact zone. However, this example is not to be considered as limiting the invention; any other appropriate step may be taken, too, in order to continuously or intermittently record changes in the characteristics of the human&#39;s visual system. 
     In one embodiment, the reaction of the person to be treated upon the presentation of one stimulus or several or many stimuli is measured, and the performance of the person is rewarded. This may happen in a way that reward points are added to a “reward account” when the responses fulfill a predetermined criterion. For example, when the person to be treated is instructed to perform as fast as possible, reward points are added to the reward account only in those cases where the response is recorded within a predetermined time delay (reaction time). Alternatively, reward points could be assigned to the reward account when a discrimination is properly made (e.g. correct form; correct colour; time discrimination). Based on the continuous recordal of the changes in the characteristics as described above, the location and definition of the intact zone is adapted to said changes. This may also be conducted continuously or intermittently. In a preferred embodiment of the invention, the number of reward points is used to automatically increase the difficulty of the next task. In this way, a means to increase the treatment difficulty is provided, depending upon the recordal of the reaction/response shown by the person to be treated. In other words: depending upon the performance of the treated person in processing the presented optical stimuli by the visual system, the intact visual zone is newly defined. Without wanting to be bound by the explanation, it can be assumed that, due to the effective treatment of the defined intact visual zone, the vision of the treated person is improved in said intact vision zone, specifically, and in general, for example by improving any function of the visual system (e.g. peripheral vision, visual acuity, ability to discriminate between different colours, shapes, movement; reduction of squinting; increase of the visual angle) or improving visual functions in general or removing partial visual system injuries. As a result thereof, the intact vision zone is enlarged or at least improved with respect to its contribution to the person&#39;s vision. As found in practice, the person to be treated experienced an improvement of the overall vision subjectively and due to a better performance in the treatment. 
     By reiterating the above-described steps, the human&#39;s intact visual field is continuously extended into zones which were previously located and defined to be transition zones. 
     Treatment may be carried out with a personal computer for use at home where persons to be treated practiced on a regular basis. In one embodiment daily treatment for 1 hr in a darkened room for an extended time period may be performed, as for example a 6-months period as employed in this test. However, any other treatment period may also prove efficacious. 
     One algorithm produces on a monitor an emission of light stimuli effecting a repetitive visual stimulation of the zone to be treated. In a first step, the zone was located, defined and characterized, i.e. there occurred a determination of the exact visual function in the zone with respect to location, size and kind. 
     Then there was defined a treatment area which is located within the zone. Said treatment area is a region within the zone where a regeneration of the neuronal structures of the person&#39;s visual system could be expected due to the results of the definition and characterization of the intact vision zone in the first step, e.g. due to the presence of a certain number of remaining neuronal structures. 
     In a subsequent step, there was conducted a stimulation of the zone based on the performance determined in the first and second steps. 
     Also, unlike prior art devices in which the program only stores the data for a later analysis, the present invention adapts, on a continuous or intermittent basis, treatment algorithms to the visual system performance in or near the zone being trained. 
     In addition, daily therapy results can be stored on suitable storing media like a tape or a disc which permits monitoring of compliance and which allows the therapy strategy to be adapted to the progress of the person. 
     The invention is hereinafter described in detail with reference to the Figures. While the description of the invention mainly relates to treating persons whose visual system is severely damaged, all details of the invention, i.e. the process and the apparatus, can be applied mutatis mutandis by a skilled person to the treatment of persons whose visual system deteriorates smoothly due to an ageing of said person and also to persons whose regular vision is to be treated in order to maintain the quality of the vision on a high level. Insofar, the description of the treatment procedure in connection to persons with a severely damaged visual system, and particularly a damaged retina, but having intact vision areas is not to be construed as a limitation of the invention. 
     In the Figures, 
       FIG. 1  shows the case of visual field treatment in a normal case where the intact vision zone has been defined to have a circular shape at least covering or even overlapping the field of the monitor frame where the target stimulus is presented. The fixation point for fixing the eyes of the person to be treated is presented in the middle of the intact vision zone, as is the target stimulus to be recognized by the person. 
       FIG. 2  shows the case where the visual system in one hemisphere does not function; the fixation point is presented in the intact vision zone, as is the target stimulus “TS 1 ”, i.e. the stimulus treatment the intact vision field, while another target stimulus “TS 2 ” is presented partly in the intact and partly in the injured field, independently. 
       FIG. 3  shows the case where the central area of the visual system (e.g. where the fovea is located) is injured (“donut-shaped visual field”). In such a case, the fixation point cannot be presented in the central area (due to the injury, it would not be recognized), but so-called “fixation ankers” are presented in the peripheral part of the blind region where the intact vision zone is located and defined. Then, a visual stimulus is presented in the intact vision zone, in this case in the form of a word. 
       FIG. 4  shows the case of a presentation of two stimuli in sequence (T 1  and thereafter T 2 ). In the same way as in  FIG. 2 , the visual field is intact in one part (I=intact visual field sector) and partially blind in another part (B=blind region). A priming stimulus (P) is preceding the target stimulus (TS 1 ) in order to increase the probability of detecting and recognizing the target. 
       FIG. 5  shows another case of a presentation of two stimuli in sequence (T 1  and thereafter T 2 ). In the same way as in  FIG. 2 , the visual field is intact in one sector (I=intact visual field sector) and partially blind in another sector (B=blind region). One of two priming stimuli P 1  and P 2  is presented to the person to be treated, and thereafter, one target stimulus (TS 1 ) is presented to the intact zone of the visual field. The person will have to respond by discriminating whether a target stimulus were presented to the intact vision field in the area of the priming stimulus. 
     The invention is explained in further detail with reference to the Figures and the preferred embodiments of Examples 1 to 5 without being restricted to these preferred embodiments. 
     The computer algorithms for the step of presenting visual stimuli to the human&#39;s visual system are such that the monitor presents a fixation point, which can be presented in any part of the monitor. The fixation point serves to a fixation of the person&#39;s view to a certain point in order to allow an adjustment of the person&#39;s angle of view. In succession, additional visual stimuli are presented in or immediately adjacent to the intact vision zone, the location of which is determined in the previous step and changed in accordance with the person&#39;s performance. In the prior art device published by Kasten et al., the visual stimuli were presented independent of the persons&#39; actual progress and were therefore inefficient and laborious. In contrast thereto, the visual stimuli are presented in the present invention predominantly in or adjacent to the intact vision zone, i.e. an area with almost no or only slight visual system injury or deteriorated vision. 
     Example 1 
     One preferred embodiment is intended for persons to be treated having a damage of the brain&#39;s visual system. For example, when the visual system in one hemisphere does not function, the opposite sector of the visual field is lost (“hemianopsia”); see  FIG. 2 . In this case, the device of the present invention would present target stimuli only in the intact vision field and not in the deficient half field. Depending upon responses to the presentation of the stimuli, increasingly more difficult target stimuli are selected to which the person to be treated has to respond until no further progress in performance can be achieved. 
     Example 2 
     Another embodiment of the invention is useful in cases where the central area of the visual system, where the fovea is located, is injured; see  FIG. 3 . This may occur after retinal damages such as age-related macular degeneration. The person to be treated sees little of nothing centrally, but has a donut-like visual field with no vision in the centre but intact vision in the peripheral part of the visual system. The device of the present invention generates target stimuli (in this case letters or words) in the intact vision zone near the visual field border, i.e. above or below the damaged region and positioned near the border. The letters or words may be stationary or moving, depending, e.g. upon the difficulty of the response requested. 
     Example 3 
     In another embodiment of the present invention (exemplified in  FIG. 4 ), a target stimulus is preceded by a priming stimulus. This could be a priming stimulus with an emotional content (e.g. a “Smiley” or “Happy Face”), which preceding priming stimulus could increase the probability of detecting the subsequent target stimulus. Both stimuli are presented to the intact vision zone of the person to be treated. In one embodiment, the priming stimulus could be presented in a very short time so that it cannot be seen consciously by the person to be treated. The person would not be asked to respond to the priming stimulus. As could be found, the presentation of a priming stimulus influences the person&#39;s ability of detection of the target stimulus. 
     Example 4 
     Another embodiment of the invention is directed to a case where two target stimuli are presented either in rapid succession or simultaneously. The response requested from the person to be treated is a discrimination whether one or several target stimuli were presented. The person would receive award points only when the discrimination problem was responded to correctly. 
     Example 5 
     In yet another embodiment of the invention, reward points are entered into the treatment person&#39;s reward account only for responses which fulfill a predetermined criterion. For example, reward points could be given only if a response is recorded by the computer within a predetermined reaction time or following the correct response to a discrimination task. Preferably, the target stimulus/stimuli is/are presented to the intact vision zone, although a simultaneous or consecutive presentation of one or more than one stimulus/stimuli to the intact vision zone and the transition zone may be possible and also in the frame of the present invention. 
     Example 6 
     In another embodiment of the invention (see  FIG. 5 ), the priming stimulus (P 1 , P 2 ) may be an attention cue such as a window frame or another object which is located at the identical position as the subsequent target stimulus (TS 1 ) presented to the intact vision zone. In this case (or also other cases), the fixation point (F in  FIG. 5 ) may be presented to the intact vision zone or the transition zone, i.e. in a zone where the person to be treated has at least sufficient vision capability to recognize the fixation point for a fixation of his eyes or to the blind zone. 
     It should be apparent from this disclosure that it is beneficial treatment to those parts or the visual field which are injured or deteriorated based on damage to the retina. Of course, the actual stimulus presented can vary in size, luminance, shape or color and it can be presented by various means, such as a projection screen, a simple computer monitor or other visual projection devices such as virtual reality goggles or helmet. The type of stimulus as well as the way by which it is presented is not limited. 
     Although the above discussion disclosed various exemplary embodiments of the invention, it should be apparent that those skilled in the art can make various modifications that will achieve some of the advantages of the invention without departing from the true scope of the invention.