Patent Grant
7988287
Not Applicable.
Traumatic brain injury (TBI) diagnosticians traditionally have relied on subjective evaluations of the degree of injury to the brain or wait for expensive, highly sophisticated instruments, like MRIs, to diagnose a patient for brain injury. In battlefield conditions access to MRIs on scene are not practical. Subjective evaluation leads to undiagnosed and untreated brain injury until the trauma has caused irreversible injury. Prompt objective diagnosis and rapid therapy to minimize the effects of the brain trauma are essential to reduce damaging side effects, reduce medical costs long term and to improve overall outcomes. The introduction of objective measurement tools will provide the clinician with the ability to quickly, reliably, and routinely determine and monitor the state of the patient's injury during the initial diagnosis and throughout the treatment and recovery process.
In addition to inflammatory, infectious or autoimmune insult of peripheral cranial nerve, nerve root or brain stem in addition to neoplastic involvement of peripheral cranial nerve, nerve root or brain stem is a significant healthcare problem worldwide. Crucial to proper treatment and prognosis is an accurate assessment of neurological function. Universally, TBI assessment is accomplished according to the Glasgow Coma Scale (GCS)1. However, this assessment is not entirely applicable to all situations and the ceiling effect associated with the GCS makes this neurologic rating scale less sensitive for monitoring milder cases of TBI2. This can lead to a delay in appropriate treatment during the critical 24 to 48 hours after a suspected TBI when secondary brain damage is most likely to occur. Examples of limitations with the GCS include intubated patients who cannot complete the verbal response category, patients with temporary paralysis, or patients who are unable to complete the motor response test, such as with those treated using the current practice of early sedation3,4. In addition, a patient's GCS rating can have significant variability from diagnostician to diagnostician owing to its largely subjective nature5, 6, 7. In a London study of emergency neurosurgical referrals, it was determined that only 51% of patients arrived with accurate GCS scores8. The inherent subjectivity of the GCS, coupled with the previously mentioned ceiling effect for mild TBI, can result in the premature discontinuation of treatment or discharge of patients still in need of monitoring or treatment. Ultimately a one-point variation in scoring can mean the difference in deciding to send a patient to a Level 1 trauma center or not, having a significant affect on the care the trauma patient receives. In response to some of these limitations, ways to improve classification of patients with TBI are being developed9. Improved TBI description will not only offer considerable value for clinical trials10,11 but will also influence clinical management and specific therapies12.
Based upon available evidence and medical understanding of the physiological factors involved, a method and system providing reproducible, objective measurements of visual system dysfunction can provide a reliable indication of Mild to Moderate levels of Traumatic Brain Injuries (MMTBI). Such data will prove useful not only in the initial diagnosis, but will have significant value for prognostic and rehabilitative purposes.
One aspect of the present invention provides a method to develop and demonstrate a field deployable instrument capable of obtaining reliable measurements of visual function that could be used in the early diagnosis of MMTBI patients.
Another aspect provides an apparatus to measure an ocular response that objectively measures visual function to detect MMTBI31. The system and method of the present invention provides one or more of the following advantages; ease of use, fast, non-invasive, and objective measurements from the initial classification of a patient's neurological state, through the early stage treatment, drug response/effect and into the rehabilitation process. The instrument's ease of use will allow for frequent monitoring of a patient's condition during longitudinal assessment thereby providing quick, reliable assessment for field and clinical environments alike.
A benefit of one embodiment of the system and method is application to the military personnel serving in today's overseas combat operation where the occurrence of MMTBI is a daily threat. The relationship between visual ocular response and specific neurological conditions has not previously been thoroughly investigated.
TBI occurs when a sudden trauma, such as a blow to the head or penetrating head injury disrupts the function of the brain. Although, numerous methods have been proposed to measure, and thus classify brain damage, the Glasgow Coma Scale (GCS) is most commonly used for initial assessment of severity of damage1. Patients with MMTBI may exhibit a range of visual system dysfunction, including binocular, oculomotor, accommodative, visual field loss, refractive error shift, and visual perceptual deficits14,15. Unfortunately, visual system assessment is often not performed during the acute stage of medical intervention; in fact, more often than not, incoming patients do not receive a thorough evaluation of their visual system at all. The reasons that visual assessments are not routinely performed include the lack of a standardized mechanism and protocol that will operate and be applicable under the largely varying situations present and the lack of an established, direct correlation with MMTBI. For example, TBI assessments are often made at different points in time and under greatly varying conditions, such as at the site of injury, during transportation to hospital, in the emergency room, or prior to admission.
Early detection of MMTBI is of particular importance to the Department of Defense. Average rates of brain injuries in deployed personnel are over twice as high as in the civilian population16,17. Inadequate diagnosis of MMTBI can have immediate consequence on operations and long-term impact on victims. Service members with no apparent symptoms after an assault or other physical injury can develop complications anywhere from 2 hours to 6 days after the initial injury18. Symptoms can include cognitive problems such as fatigue, irritability, anxiety, dizziness and visual disturbances, which can affect the ability to function, especially in a high-stress combat situation19,20,21,22,23,24. These individuals are at risk of being inadvertently returned to duty and presenting an adverse risk to themselves, their comrades and their missions.
The preferred diagnostic technique for head injuries in Combat Support Hospitals (CSH) is structural imaging using computerized tomography (CT). CT imaging provides more clinical information than can be obtained from physical examination of a patient. Unfortunately CT imaging may show as negative for mild to moderate trauma. Magnetic Resonance Imaging (MRI) is often the preferred diagnostic technique for other neurologic insults, or disease. With the addition of MRI, especially when integrated with single-photon emission computed tomography, measurements can more accurately show the physiological extent of a lesion, disease or other neurologic injury of the brain25. This outcome, which can be true even for MMTBI, assumes that a patient has been first, adequately identified as a potential MMTBI case, and second, enough time has passed that an identifiable lesion has formed. Even so, the physical size, operational complexity, and logistics of MRI preclude its use in every CSH. Thus, a new system and method for clinical and research use suitable for field use is required to bridge the gap between CT and MRI.
An objective technique for reliable and repeatable assessment of ocular response to access central and peripheral neurological function in potential MMTBI patients for example, would provide a complementary test of neurological function.
One embodiment of the present invention provides an ophthalmic examination device comprising a wavefront sensor aligned with an eye of a patient through a first optical path; a target aligned with the eye through a second optical path; a pupil imager aligned with the eye through the first optical path or the second optical path; wherein the wavefront sensor is positioned to measure the variation in the wavefront reflected from the retina of the eye via the first optical path. In a preferred embodiment a fundus imager is aligned with the eye through the first optical path or the second optical path. The target may be a physical target or a virtual target. A deformable mirror in the second optical path may produce changes in the position of the virtual target. Alternatively a mirror is mechanically altered to move the target to a new physical location. In another embodiment a deformable mirror in the first optical path, the second optical path or a combination thereof provides correction of refractive error. In yet another embodiment an illumination source is co-aligned to the first optical path, the second optical path or a combination thereof. In a more preferred embodiment, the device further comprises a binocular wherein both eyes share a common optical path to the target. In this embodiment, a mirror for correction of refractive error may be in the common path.
Another embodiment of the invention provides a method for determining neurological function of a patient comprising the steps of automatically measuring accommodation in both eyes of a patient simultaneously comprising presenting a target within an ophthalmic examination device to an eye of a patient to focus upon wherein the target is in a first position of the ophthalmologic examination device. A first wavefront of reflected light from the eye focused upon the target is measured using a wavefront sensor aligned with the eye via a first optical path. The target is moved to a second position while the eye is focused upon the target. A change in the wavefront measured from the eye when the target is moved to the second position is compared to the wavefront measured from the eye focused upon the target in the first position. A response time is determined of the eye to follow the target from the first position to the second position to determine the accommodation of the eye. In a preferred embodiment the response time for accommodation of the eye is compared to a database of control accommodation to produce an accommodation score.
Another embodiment of the present invention provides a method for determining neurological function comprising the steps of: automatically measuring saccades in both eyes of a patient simultaneously comprising: presenting a target within an ophthalmic examination device to an eye of a patient to focus upon wherein the target is in a first position of an ophthalmologic examination device. An eye tracking vector is calculated for each eye independently as each eye is focused upon the target. Motion of the vector is measured over time to determine saccades. In a preferred embodiment a movement above predetermined cutoff frequency is measured. In a more preferred embodiment a database of normal saccades to produce a saccades score.
Yet another embodiment of the present invention provides a method for determining neurological function comprising the steps of: automatically measuring vergence efficiency in both eyes of a patient simultaneously comprising: a) presenting a target within an ophthalmic examination device to an eye of a patient to focus upon; b) calculating an eye tracking vector for each eye independently as each eye is focused upon the target; c) determining the intersection of the left eye vector and right eye vector focused upon the target in a first position in comparison to the actual target position within the ophthalmic examination device; and d) determining the tracking accuracy of each eye by determining offset of an eye vector in comparison to calculated target position to determine vergence errors. In a preferred embodiment steps a)-d) are repeated as the target is moved to a second position; and vergence efficiency at a plurality of intermediate positions between the first and second target position is measured. In a more preferred embodiment, a movement below a predetermined cutoff frequency is measured. In yet another embodiment, the vergence errors determined are compared to a control database of vergence errors to produce a vergence efficiency score.
Yet another embodiment provides a method for determining neurological function comprising the steps of: automatically determining smooth pursuit in both eyes of a patient simultaneously comprising: presenting a target within an ophthalmic examination device to an eye of a patient to focus upon wherein the target is in a first position of an ophthalmic examination device; calculating an eye tracking vector for each eye independently as each eye is focused upon the target to produce a left eye vector and a right eye vector; determining the intersection of the left eye vector and right eye vector focused upon the target in comparison to the target position within the ophthalmic examination device; moving the target in a pattern; comparing each eyes temporal eye tracking of the moving target over time; and determining temporal correlation of each eyes movement to the moving target to determine smooth pursuit of each eye as an indication of neurological function. The pattern may be random or non-random. In a preferred embodiment a score as to the calculated smooth pursuit of each eye of patient is compared to a database of control values to produce a smooth pursuit score.
Yet another embodiment provides a method for determining neurological function comprising the steps of: automatically measuring pupillary response comprising: determining pupil size of each eye independently in a first light condition with a device as described in
Still another embodiment provides a method for determining neurological function of a patient comprising the steps of: generating a score reflective of the neurological function of a patient based upon one or more scores selected from eye accommodation score, eye vergence score, eye saccades score, eye smooth pursuit score, pupillary response score or any combination thereof to determine the neurological function of the patient.
In yet another embodiment, measurements of the eye are not taken simultaneously but are taken independent of the other eye.
It is an aspect of the present invention to evaluate neurological function with a system and method to monitor one or more of the following: accommodation, pupillary response, vergence, saccades, smooth pursuant using a field deployable instrument capable of obtaining reliable measurements of visual function that could be used in the early diagnosis of patients with brain injury, neurological disease or a combination thereof. For example, stroke, Multiple Sclerosis, Amylateral Sclerosis, polyneuropathy, mononeuritis multiplex, meningitis, head trauma.
On object of the present invention provides for a system and method for evaluating neurological function in patients having, stroke, Parkinson's, Post Traumatic Stress Disorder (PTSD), sports injuries and drug efficacy and toxicity.
Another aspect of the present invention provides an ophthalmic examination device to measure an ocular response that objectively measures neurological function to detect brain injury, neurological disease or a combination thereof. One embodiment of the present invention provides one or more of the following; ease of use, fast, non-invasive, consistent, and objective measurements from the initial classification of a patient's neurological state, through the early stage treatment through the rehabilitation process.
Another object of the present invention provides for ease of use of an ophthalmic examination device for frequent monitoring of a patient's condition during the entire treatment process, providing quick, reliable assessment for field and clinical environments alike.
Additional objects and advantages of the present invention will be apparent in the following detailed description read in conjunction with the accompanying drawing figures.
Many aspects of visual functioning require communication among widely separated areas of the brain. The pathways connecting the retina to the primary visual cortex traverse its entire length. Injury to white matter connecting these widely spread vision-related areas may result in visual field deficits, changes in color vision, and/or oculomotor dysfunction. Oculomotor systems which govern eye movements and include vergences, accommodation, and versions, involve both brainstem, cortical and subcortical processing. Functional imaging studies have implicated multiple areas, including the paramedian pontine reticular formation, vermis of the cerebellum, superior colliculus, frontal and parietal eye fields, dorsolateral prefrontal cortex, visual cortex, vestibular cortex, basal ganglia and thalamus.
Injury to white matter connecting widely spread vision-related areas may result in visual field deficits, changes in color vision, and/or oculomotor dysfunction (e.g., vergence, accommodation, saccades, smooth pursuit), collectively termed the post-trauma vision syndrome.
A meta-analysis of three clinically measurable oculomotor associated functions from four (4) studies containing a combined population of control and TBI patients was performed. Oculomotor outcome variables (accommodation, vergence, and version) were measured. Pooled risk ratios for the incidence of accommodative abnormalities in subjects with TBI compared to subjects without TBI indicate an increased incidence in the subjects with TBI. Dispersion was uniform. Pooled risk ratios for the incidence of vergence abnormalities in subjects with TBI compared to subjects without TBI indicate an increased incidence in the subjects with TBI. Dispersion was uniform. Pooled risk ratios for the incidence of versional abnormalities in subjects with TBI compared to subjects without TBI indicate an increased incidence in the subjects with TBI. Dispersion was uniform.
The Mantel-Haenszel methods (the default fixed effect methods of meta-analysis programmed in RevMan) were used. Using this method, data from each study is weighted based on several parameters including the effect measure (relative risk (RR) in this case) and study size. The effect size represented as rate of an event in TBI/rate of an event in non-TBI control ranged from approximately 3x-7.7x.
The relative risks for dysfunctions of accommodation, vergences were described, thus allowing a metric as to the use of these oculomotor functions in the detection of TBI or as associated clinical predictors. For the meta-analysis the RevMan software was used in keeping with Cochrane Collaboration guidelines. All three measures of oculomotor function were significantly affected in TBI, with the greatest effect size occurring in vergence, followed by versions, and then accommodation. Heterogeneity in selected studies was estimated using I2=[(Q df)/Q]×100%, where Q is the chi-squared statistic and df is its degrees of freedom. The resulting percentage describes the variability in effect estimates that is due to heterogeneity rather than sampling error (chance). A value greater than 50% is usually considered substantial heterogeneity. All I2 values in this study were less than 50% signifying great levels of homogeneity among included studies. Based upon Applicant's observations a system and method for measuring neurological function of a patient with an embodiment of an ophthalmic examination device is described.
One embodiment of the present invention provides an ophthalmic examination device. Referring now to
In a preferred embodiment both eyes are examined simultaneously with a binocular non-mydriatic ophthalmic examination device. In a more preferred embodiment, both eyes are examined simultaneously while observing a target in a common optical path. In a more preferred embodiment control data collection and data processing system 119 obtains information from one or more components 115, 113, 109, 107, 111 for measuring visual system efficiency such as defocus and spherical aberration measurement, high resolution eye tracking, virtual target projection to determine accommodation, vergences, saccades, smooth pursuit of eye and pupillary response from both eyes simultaneously, however, the device is not limited thereto as each eye can be observed independently in using a monocular device. However by simultaneously measuring both eyes for multiple parameters the patient is not fatigued with exposure to multiple instruments over time and improved measurements can be obtained.
An illumination source is co-aligned to a first optical path, a second optical path, or a combination thereof. An illumination source can be tuned to a wavelength that stimulates the eye or that is non-stimulating to the eye.
Real-Time Accommodation: Real time measurement of the aberrations in patients' eyes are observed, measured, determined, scored or some combination thereof with an ophthalmic examination device according to one embodiment of the present invention.
One embodiment of the present invention utilizes a wavefront sensor to generate defocus and spherical aberration measurement measurements. In a preferred embodiment, the wavefront sensor is a distorted grating wavefront sensor. The distorted grating wavefront sensor has several advantages, one of which is that the data to generate the aberration information is contained in a single, small-size image as compared to the amount of data required with a Shack-Hartman wavefront sensor. As very little data needs to be collected as compared to data collection with a Shack-Hartman wavefront sensor, the detector used can be rugged, inexpensive, and be operated at very high data acquisition rates for example a camera can be operated at high frame rates. Additionally, the processing algorithm used for the reconstruction of the aberration map is very insensitive to scatter sources that may be present in the eye31. Such advantages allow not only improved measurement of static accommodation in refractive accommodations, but also measurement of dynamic accommodation obtained as the subject refocuses between distances. Referring now to
One of the common complaints associated with brain injury or disease is blurry vision. The blurry vision can be the result of neurological impairments, but it is also important to be able to conclusively rule out physiological (functional) causes for this impairment, such as refractive errors as a result of the injury, elevated pressures or pre-existing conditions in the patient. To rule out these problems, in a preferred embodiment, the system and method of the present invention are initially adjusts to provide refractive error correction. This correction can be done manually, much as is done by manual adjustments of binoculars. Alternatively, wavefront sensing and adaptive optics include an adaptive-optics based refractive correction upon system initialization. This system and method will ensure that vision defects and dysfunctions measured by the device are neurological.
Another embodiment provides for a dynamically varying target that can be seen by the patient. In one example, a liquid crystal display and projection optics allow the system to simulate targets that the patient will visualize at different distances and positions in the visual field. Varying the range of the target's apparent distance will stimulate the subjects' accommodation function enabling the aberrometer to obtain real-time measurements of accommodation.
Eye Tracking: Oculomotor function as an indicator of neurological function will be measured with improved resolution eye tracking having an improved degree of angular accuracy. Typically eye tracking systems are based on measurements made from a reference point within the pupil or on the cornea using either infrared or visible light. While these systems are ideal for general eye tracking applications, such as vision research26, the accuracy of these systems is poor (0.5° typically). Such an error corresponds to an error distance of, approximately, 17 mm for a fixation distance of 2 m. This is clearly not accurate enough to observe the subtle defects in visual function such as double-vision that can occur from brain injury or disease such as MMTBI or other central and peripheral brain disease. For such measurements a very high degree of angular accuracy is required. For example, to achieve a measurement displacement of 1.7 mm at a 2 m fixation point, an angular accuracy of 0.05° is preferred, which is an order of magnitude smaller than that of currently available eye tracker systems. Referring now to
One embodiment of the present invention provides for a combined pupil and retina mapping technique. Referring now to
A target within the device allows the observer to measure the eyes accommodation as the target is in a static position and also when the target is repositioned. Referring now to
In conjunction with information about the position of the target the accuracy of the visual direction of the two eyes relative to the target is calculated, and therefore a measure of the vergence characteristics is obtained. A vergence is the simultaneous movement of both eyes in opposite directions to obtain or maintain single binocular vision. The two eyes converge to point to the same object. When a creature with binocular vision looks at an object, the eyes must rotate around a vertical axis so that the projection of the image is in the centre of the retina in both eyes. To look at an object closer by, the eyes rotate towards each other convergence, while for an object farther away they rotate away from each other divergence. Exaggerated convergence is called cross eyed viewing (focusing on the nose for example). When looking into the distance, the eyes neither converge nor diverge. Vergence movements are closely connected to accommodation of the eye. Under normal conditions, changing the focus of the eyes to look at an object at a different distance will automatically cause vergence and accommodation.
Measurements of the instantaneous change of eye position can be monitored, as a target is switched from one position to another. The measurements will characterize the performance of the eyes individually and operating in concert, giving an accurate, objective assessment of any deficiency due to MMTBI or other central or peripheral disease or injury. The target can be a physical object or an image of a virtual target. In a preferred embodiment the target is a virtual target whose virtual position is changed with deformable mirrors.
Referring now to
In another embodiment, the wavefront sensor and a deformable mirror system are the components needed to realize adaptive optics correction of refractive defects and make it possible to correct basic refractive errors as well as more complex problems such as oblique astigmatism that can render a patient unsuitable for fundus imaging. The adaptive optics correction also addresses issue of clarity of image being due to something other than neurological dysfunction.
Real Time Visual Stimulus: One embodiment of the present invention provides for measuring eye performance parameters. For example, a patient is asked to focus on a target that the subject can visualize. Traditionally these targets have been marks or small objects that are moved by the clinician. To measure the speed performance of the eye, a new type of target is required. The target changes position or range rapidly and at a precisely known point in the measurement sequence. One embodiment of the invention provides an automated target that is responsive to the measurement taken, the instructions of an algorithm operated on a computer and or the user.
It is known that the eye of a normal subject has a response-to-stimulus latency of approximately 360 ms, a fixation time from far-to-close of about 640 ms, and a time from close-to-far of 560 ms27. To measure these response times a target will be “moved” in time periods much smaller than this, on the order of tens of milliseconds. In a preferred embodiment the interval is less than 100 ms. In a more preferred embodiment the interval is between about 10-100 ms.
Referring now to
For example, vergence measurements are acquired from both eyes while observing the same object which will require the two eyes to observe the object through the same optical path within an ophthalmic examination device. A preferred embodiment of the ophthalmic device includes a non-mydriatic binocular. This will ensure that both eyes of a patient are properly converging to the same point in object space. A common path configuration will avoid the possibility of convergence errors due to misalignment in the equipment, which would be possible when using a separate target for each eye. It is also possible to envisage a setup where there are two targets that are adjusted independently with each eye observing a separate target.
Referring now to
According to one embodiment of the present invention, a virtual target system has a response times far shorter than the accommodation time of the eye as discussed above. This allows measurement of the time taken for the eye to adjust to the target position. Due to the short time scale as discussed above, traditional adjustable optics based on mechanical movement of lenses is not preferred, so the use of deformable mirrors is preferred. Traditionally, deformable mirrors have been developed to combat the effects of atmospheric turbulence on the imaging performance of large telescopes. Based on the small mechanical actuation of a semi-flexible mirror it is possible to very accurately control the light reflecting off the surface. By controlling just the defocus term, these mirrors make an ideal candidate for an optical system that is instantly reconfigurable. Using several mirrors in conjunction will create a virtual target that can move to a protocol-defined distance from the observer. Particularly for measurement systems used for the eye, adapting to the individual peculiarities of each eye is frequently an essential precondition for eliminating or limiting sources of error or even the precondition for results capable of evaluation.
Referring now to
Another common observed ocular defect is asymmetric pupils after concussion. One embodiment of the present invention images the pupil to determine location and centroid. Simultaneously, the image processing system can return the sizes of both pupils in response to the same stimuli, rather than performing independent pupillometry measurements in those situations where the additional information can enhance the understanding of the patient's condition by detecting assumptive or delayed stimulus responses. Referring now to
The entire disclosures of all references, applications, patents, and publications cited above and/or in the references, and of the corresponding application(s), are hereby incorporated by reference.
This application claims priority to and the benefit of the filing of U.S. Provisional Patent Application Ser. No. 60/948,656, entitled “Objective Traumatic Brain Injury Assessment”, filed on Jul. 9, 2007, and the specification and claims thereof are incorporated herein by reference. This application is a continuation-in-part of U.S. patent application Ser. No. 10/981,996, entitled “Ophthalmic Aberrometer for Measuring Aberrations in the Eye” filed on Nov. 4, 2004, and the specification and claims thereof are incorporated herein by reference.
| Number | Name | Date | Kind |
|---|---|---|---|
| 6595642 | Wirth | Jul 2003 | B2 |
| Number | Date | Country | |
|---|---|---|---|
| 60948656 | Jul 2007 | US |
| Number | Date | Country | |
|---|---|---|---|
| Parent | 10981996 | Nov 2004 | US |
| Child | 12170374 | US |
