Abstract:
A method and system for detecting eye disease. A pattern is displayed on a screen to an individual, who is made to fixate his vision on a point in the pattern. The pattern is then hidden and a second pattern is displayed. The individual then compares the second pattern, as perceived by him, with a pre-defined pattern. These steps are then repeated several times. It is then determined whether the individual has an eye disease based on the comparisons.

Description:
FIELD OF THE INVENTION 
     This invention relates to systems and methods for detecting eye disease. 
     BACKGROUND OF THE INVENTION 
     Age-related macular degeneration (AMD) is the leading cause of blindness among people over the age of 50 in the western world. It is a bilateral, although asymmetric disease, and comes in two forms: 
     Dry or non-neovascular AMD is the more common and milder form of AMD, accounting for 85-90% of all AMD. The key identifier for dry AMD is small, round, white-yellow lesions in the macula. Vision loss associated with dry AMD is far less dramatic than in the case of wet AMD. There is currently no treatment available for dry AMD. It is estimated that as many as 14 million people suffer from dry AMD in the United States alone. 
     Wet AMD is less prevalent than the dry form, accounting for about 10-15% of AMD cases. The term wet denotes choroidal neovascularization (CNV), in which abnormal blood vessels develop beneath the retinal pigment epithelium (RPE) layer of the retina. Wet AMD is characterized by the development of choroidal angiogenesis which causes severe, and potentially rapid, visual deterioration. The visual distortion typically consists of perceiving straight lines as curved due to deformation of the retina in a region overlying the choroidal angiogenesis. The wet form accounts for about 60% of all cases of adult blindness in the United States. In the US alone there are 200,000 new cases of wet AMD every year and a total of 1.7 million blind people from AMD. 
     Treatment modalities for wet AMD include conventional treatments such as laser photocoagulation and newer treatment modalities such as PhotoDynamic therapy (PDT). Experimental treatments that are under current investigation include feeder vessel coagulation and Trans-pupillary ThermoTherapy (TTT). All these proven or experimental therapies may halt or slow progression of the disease only if detected at an early stage and will not reverse existing retinal damage. Therefore, early detection is crucial to prevent severe visual loss. 
     Since approximately 12% of dry AMD cases develop wet AMD and subsequent blindness within 10 years, a patient diagnosed with dry AMD must be routinely examined by an ophthalmologist once or twice a year, depending on the severity of his condition. The patient is usually also given a so-called “Amsler grid” for weekly self-examination at home for symptoms of wet AMD. The patient is advised to consult an ophthalmologist immediately in the event that symptoms are noticed. The Amsler grid and its modifications (such as the “threshold Amsler” or the “red Amsler”) have been displayed to be poor detectors of early changes associated with wet AMD for several reasons. One is the phenomenon of “filling-in” whereby the brain fills in missing parts in the pattern or corrects defects in the pattern. The subject thus fails to perceive a distorted pattern as being distorted. Another problem with the Amsler grid is the inability of patients to adequately fixate their vision on a fixed point while taking the test. The Amsler test also suffers from low compliance stemming from the non-interactive nature of the test. 
     The degree of visual deterioration is a function of the size of the lesion and its proximity to the fovea at the time of diagnosis. Although most lesions probably start outside the foveal area, 70% are already foveal and large (&gt;1500 microns) at the time of diagnosis. It is therefore crucial to identify the lesions at the earliest possible stage, while they are still small and have not reached the fovea. It is known that 70% of lesions diagnosed as treatable become untreatable within less than three months, which indicates that the progression of the disease is relatively rapid. As many as 70-80% of patients with wet AMD are already ineligible for treatment when they first consult their ophthalmologist because the disease has progressed considerably. This is due to the poor validity of existing self-assessment methods for detecting an AMD-related lesion at an early stage, and the time lapsed between noticing the symptoms and seeing an ophthalmologist. 
     A reliable method for diagnosing wet AMD at the earliest possible stage, in conjunction with a referral system aimed at lowering the incidence of visual deterioration in this devastating disease, are imperative. If detected early, laser therapy to destroy the abnormal blood vessels may prevent additional vision loss. It is therefore crucial to detect the transition from dry to wet AMD as early as possible. 
     SUMMARY OF THE INVENTION 
     The present invention provides an eye test for detecting retinal lesions such as those associated with AMD or diabetes. The method involves showing a subject a first pattern displayed on a surface. The pattern may be, for example, one or more lines. The subject then fixates his vision on a point on the surface. The first pattern is hidden and a second pattern is displayed at a different location on the surface. The second pattern may be substantially identical to the first pattern, or the two patterns may be different. The subject is then asked to compare the second pattern and a predefined pattern. If the second pattern and the predefined pattern were identical, but the subject has perceived them to be different, this is indicative of a lesion of the retina. The subject indicates a region in the second pattern that appears to him to be different from the same region in the predefined pattern. The location of the lesion on the retina is determined from the location of the region in the second pattern on the surface relative to the point where the subject&#39;s vision was fixated. If the second pattern and the predefined pattern were not identical, but the subject reports that the two patterns were identical, this would indicate that he is not responding reliably to the test. Thus, the second pattern may be obtained by modifying the predefined pattern to simulate the predefined pattern as perceived by a person with an eye disease. For example, the second pattern may be obtained from the predefined pattern by displacing a component of the predefined pattern, removing a component of the predefined pattern, blurring a component, or altering an optical property of a component of the predefined pattern, such as color or intensity. Such modified patterns may also be used to demonstrate to subjects various types of visual disturbances associated with retinal lesions. 
     Since the subject will spontaneously shift his vision to the second pattern within about 200 msec after it appears, the subject may additionally or alternatively be asked to indicate whether any motion occurred of part of the second pattern relative to other parts of the second pattern as he shifted his vision, and if so, where in the second pattern the motion occurred. For example, a segment of a line that appears curved when in the periphery of the subject&#39;s field of vision may appear to straighten as the subject shifts his vision and brings the pattern into the center of his field of vision. This apparent movement at the particular location in the pattern as the subject shifts his vision is indicative of a retinal abnormality in the corresponding region of the retina. 
     The test is repeated several times, each time presenting the second pattern in a different region in the subject&#39;s field of view. This allows a retinal abnormality to be mapped on the retina. 
     In a preferred embodiment, the method is performed by displaying the patterns on a monitor screen such as a computer monitor, television, or stand-alone device. In this embodiment, the subject can be made to fixate his vision on a point of the screen by having him bring a cursor to the point on the screen using any computer input device such as a computer mouse, a keyboard, joystick or touch-screen. This causes the first pattern to disappear from the screen and for the second pattern to appear. The patterns may consist of one or more broken lines consisting of a plurality of segments. The subject indicates a segment in the second pattern that appears different to him than the corresponding segment in the first pattern by bringing the cursor to the point and clicking the mouse. For example, if the first and second patterns are broken lines, and the subject perceives the first pattern as being straight, but perceives the second pattern as having one or more unaligned segments, the subject would click the unaligned segments with the mouse. 
     The results of the test are typically transmitted in real time over a communications network to a processor. The network may be a computer network such as the Internet, local and wide are networks such as LAN, WAN, or PAN. The network may also be a telephone network using a modem and TCP/IP connection. The processor that analyzes the subjects responses and generates a diagnosis of the subject&#39;s condition. The diagnosis and a recommendation for follow-up or referral for prompt examination are then transmitted over the communication system to the subject and to his care provider. The subject&#39;s compliance may be monitored regularly by the processor by storing in a memory the dates that the subject is to perform the test. Failure to perform the test on schedule results in a reminder being sent to the subject over the communication network or by telephone to perform the test. A notice may also be sent to the health care provider. 
     Thus, in its first aspect the invention provides a method for detecting eye disease in an individual, comprising steps of: 
     displaying to the individual a first pattern at a first location on a surface, the first pattern consisting of at least one point; 
     fixating the individual&#39;s vision on a point in the first pattern; 
     hiding at least a portion of the first pattern; 
     displaying a second pattern to the individual at a second location on the surface so as to allow the individual to form a perceived image of the second pattern; 
     obtaining a comparison of the perceived image and a predefined pattern; 
     repeating the first step of displaying, the step of fixating, the step of hiding, the second step of displaying, and the step of obtaining a number of times; and 
     determining whether the individual has an eye disease based on the comparisons. 
     In its second aspect, the invention provides a system for detecting eye disease in an individual, comprising; 
     (a) a surface configured to display a first pattern to the individual, the pattern consisting of at least one point; 
     (b) a device for fixating the individual&#39;s vision on a point in a pattern displayed on the surface and hiding the pattern after the individual&#39;s vision has been fixated on the point; and 
     (c) a device for selecting a portion of a pattern displayed on the surface. 
     In its third aspect, the invention provides a program storage device readable by machine, tangibly embodying a program of instructions executable by the machine to perform method steps for detecting eye disease in an individual, comprising steps of: 
     displaying to the individual a first pattern at a first location on a surface, the first pattern consisting of at least one point; 
     determining when the individual&#39;s vision is fixated on a point in the pattern; 
     hiding at least a portion of the first pattern upon the individual fixating his vision on a point in the first pattern; 
     displaying a second pattern to the individual at a second location on the surface so as to allow the individual to form a perceived image; and 
     obtaining a comparison of the perceived image and a predefined pattern; 
     In its fourth aspect, the invention provides a computer program product comprising a computer useable medium having computer readable program code embodied therein for detecting eye disease in an individual, the computer program product comprising: 
     computer readable program code for causing the computer to display a first pattern to the individual at a first location on a surface; 
     computer readable program code for causing the computer to determine when the individual&#39;s vision is fixated on a point on the surface and for hiding at least a portion of the first pattern when the individual&#39;s vision is fixated on the point; 
     computer readable program code for causing the computer to display a second pattern to the individual at a second location on the surface so as to allow the individual to form a perceived image of the second pattern and; 
     computer readable program code for causing the computer to obtain a comparison of the perceived image and the predefined pattern. 
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS 
     In order to understand the invention and to see how it may be carried out in practice, a preferred embodiment will now be described, by way of non-limiting example only, with reference to the accompanying drawings, in which: 
     FIG. 1 is a system for detecting eye disease in accordance with one embodiment of the invention; 
     FIGS. 2A-2B are flow chart diagrams for a process of executing an eye test in accordance with one embodiment of the invention; 
     FIG. 3 are exemplary screens displayed on a computer monitor while carrying out the process of FIG.  2 . 
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     FIG. 1 shows a system for carrying out the invention according to one embodiment of the invention. A subject  100  performs an eye test using a computer terminal  105 . The computer  105  comprises a computer  110 , a monitor  115  having a screen  112  and one or more computer input devices such as a keyboard  120  or a computer mouse  125 . The computer  105  communicates over a communication network indicated by the cloud  130 . The network  130  may be, for example, the Internet, a local area network (LAN) or an Intranet. 
     A processor  135  in a network server  140  stores data relating to execution of an eye test to be performed by the subject  100  to be described in detail below. The eye test is communicated from the server  140  to the subject&#39;s computer  105  over the network  130 . The subject  100  inputs responses to the eye test using one or more of the computer input devices such as the keyboard  120  or the mouse  125 . The subject&#39;s responses are communicated over the network  130  to the processor  135 , and stored in the memory  145 . The processor is configured to analyze the subject&#39;s response, to make a diagnosis of the subjects conditions and to recommend future follow-up or recommend prompt examination, all in real time, for the subject. The diagnosis and recommendation are communicated over the network  130  to the subject&#39;s terminal  105  and/or to a terminal  150  of a health care provider  155 . The processor  135  is also configured to store in the memory  145  dates on which the subject is to perform an eye test executed by the processor  135 . If, for example, the subject  100  has been instructed by the health and provider  155  to perform the test once per week, the processor  135  may send a message over the communication network  130  when 10 days have elapsed since the last time he took the test, informing the subject of his failure to take the test as instructed. A similar message may be sent to the health care provider  155 . A responsible individual may be designated, in such a case, to contact the subject  100 , for example, by telephone to clarity why the subject  100  has not performed the test as instructed and to impress upon the subject the importance of performing the test as indicated. 
     FIGS. 2A and 2B show a flow chart diagram for a process of executing an eye test over a system such as the one shown in FIG. 1, in accordance with the invention and FIG. 3 shows the appearance of the screen  112  of the subject&#39;s monitor  115  at various steps of the eye test. 
     In step  200 , the subject  100  logs onto the processor  135 . The processor  135  causes log-on screen  300  to be displayed on the subject&#39;s monitor  115  (step  205 ). The log-on screen  300  screen prompts the subject to input his name into a field  302  and a previously assigned password for accessing the processor  135  into a field  304 . In step  210  the subject inputs his name and password using computer input devices such as the keyboard  120  or the mouse  125 . The processor  135  then checks whether the inputted name and password are stored in the memory  145  (step  215 ). If no, processor determines whether the number of attempts the subject has made to input a name and password is less than a predetermined number such as 3 (step  220 ). If yes, the process returns to step  205 . If no, the process terminates. 
     If at step  215  the processor determines that the name and password are in the memory  145 , the process continues in step  248  by the subject covering an eye, so that the test is performed using one eye only. In step  250  a form screen  320  is displayed in which a pattern such as line  322  is displayed. This is by way of example only, and any pattern may be used within the scope of the invention. The pattern may consist of a single component, or consist of several components which may or may not be all identical. Thus, the pattern may consist of several lines, one or more circles, lines and circles together, etc. The screen of the monitor  115  may form a visually noisy background to a displayed pattern. The line  322  may be composed of several short segments, for example, the segment  224 . Alternatively, the line may be continuous (not shown). The length of the line is preferably 1-20° in length, and may be horizontal as the line  322 . Gaps between the segments are preferably between 0 to about 120 minutes arc. If the pattern consists of two or more parallel lines, the spacing between the lines is preferably from about 10 to about 600 minutes arc. The line may be vertical or slanted (not shown). A marker  228  is adjacent to one of the segments, for example the segment  229 . 
     The subject is instructed to bring a cursor  225  appearing on the screen to the marker  228 . In order to aid the subject, the cursor is restricted in its position to a line parallel to the line  322  so that the cursor always points to one of the segments. The subject performs this in step  255  using a computer device such as the keyboard  120 , or more preferably the mouse  125 . The marker  228  is sized so that it is large enough to see but small enough so that bringing the cursor  225  to the marker  228  is a demanding task for the subject. This causes the subject to fixate his vision on the marker. Upon bringing the cursor to the segment  229 , the subject may click on his mouse  125  or depress a predetermined key on the keyboard  120  (step  260 ). 
     When the subject inputs that the cursor is positioned at the marker  228 , indicating that his vision is fixated on the segment  229 , the line  322  is made to disappear from the screen  320  (step  265 ). After a predetermined time interval (for example 0 to 200 milliseconds), a second pattern  332  is made to appear at a different location as shown in screen  330  (step  270 ) so as to allow the subject to form a perceived image of the second pattern  332 . In this example, the pattern  332  is a line identical to the line  322  but appearing in a different location on the screen  112 . The line  332  may, for example, be parallel to the line  322 . Since the subject&#39;s vision had been fixated on the segment  229 , the line  332  will appear in the periphery of the subject&#39;s field of vision. Any disturbance in his vision due to a retinal lesion such as AMD is apparent to the subject as a difference between the perceived image of the second pattern and a pre-defined pattern, which in this example is provided by the first pattern. For example, when the subject&#39;s vision is fixated at the location where the segment  229  had previously appeared (the point  342  in screen  340 ), a segment  344  of the line  332  may appear to be out of line with other segments in the line  332 . Screen  340  shows a possible appearance of the screen  330  to an individual having a retinal lesion. In screen  340 , the segment  344  is out of line with other segments in the line  332 . This is by way of example only, and other differences between the perceived image and the pre-defined pattern may occur, such as a segment appearing blurred to the subject in the second pattern. As the subject subsequently shifts his vision to the line  332 , the segment  344  appears to move into alignment with other segments in the line  332  as shown in screen  350 . 
     The subject, in step  275 , indicates which, if any, of the segments in the line  332  appeared different than corresponding segments in a predefined pattern. This may be done by the subject bringing the cursor  225  to the segment that appeared to move (the segment  344  in this example). This implicates the region in the subject&#39;s retina corresponding to the direction of the segment  344  as having a retinal lesion. 
     In step  280  it is determined whether the number of lines  322  presented to the subject is less than a predetermined number, such as  40 . If yes the process returns to step  250  with a new line  322  being presented to the subject. Steps  250  to  280  are repeated several times, for example 40 times each time presenting the line  332  in a different location of the screen until the region of the subject&#39;s macular visual field has been completely mapped. 
     If it is determined in step  280  that the number of lines presented to the subject has reached the predetermined number, it is determined whether only one eye has been examined so far (step  285 ). If yes, the subject is instructed to uncover his eye and to cover the other eye ( 288 ). The process then returns to step  250  with the subject testing his other eye. If no, the process terminates at step  290 . 
     The position of the line  322  presented to the subject is varied each time in order to completely cover the fovea so as to detect any regions affected with AMD. Areas are preferably mapped more than once, and at a higher resolution (several successive lines  322  relatively close to one another). 
     As shown in screen  360 , instead of the line  332  having only aligned segments, a line  362  actually having a displaced segment  364  may be presented to the subject, for example, for a duration up to about 300 msec. This is done to ascertain that the subject is aware of the visual associated with AMD, and that his responses reliably reflect the perceived appearance of lines presented to him. 
     It will also be understood that the system according to the invention may be a suitably programmed computer. Likewise, the invention contemplates a computer program being readable by a computer for executing the method of the invention. The invention further contemplates a machine-readable memory tangibly embodying a program of instructions executable by the machine for executing the method of the invention.