Apparatus and method for diagnosis of optically identifiable ophthalmic conditions

This application claims priority to and the benefit of co-pending U.S. provisional patent application Ser. No. 61/047,935 filed Apr. 25, 2008, which application is incorporated herein by reference in its entirety. This application is also related to U.S. patent application Ser. No. 10/697,454 filed Oct. 30, 2003 and U.S. patent application Ser. No. 11/224,774 filed Sep. 13, 2005, each of which applications is incorporated herein by reference in its entirety.

This invention resulted from work under a joint research agreement between the Assignee of the present application and Andrew Saykin of Indiana University, Center for Neuroimaging, Dept. of Radiology. Indiana University School of Medicine, 959 W. Walnut St. R2EH24, Indianapolis. Ind. and Laura Flashman, Dartmouth College, Dept. of Psychiatry, Dartmouth College Medical School, Lebanon, N.H.

1. Field of the Invention

The invention relates to testing for physiological and neurological conditions in general and particularly to systems and methods that employ optical eye tests and the responses of individuals to visual stimuli.

2. Description of Related Art

Numerous systems and methods are known for examining states of health of eyes. For example, U.S. Pat. No. 5,065,767, issued Nov. 19, 1991 to Maddess, discloses a psychophysical method for diagnosing glaucoma that employs a time varying contrast pattern. Glaucoma may be indicated for an individual who displays a higher than normal contrast threshold for observing the pattern. Maddess also discloses other tests for glaucoma such as the well-known observation of a scotoma, measurement of intraocular pressure, and assessment of color vision defects. U.S. Pat. No. 5,295,495, issued Mar. 24, 1994 to Maddess, discloses systems and methods for diagnosing glaucoma using an individual\'s response to horizontally moving stripe patterns, which is known as optokinetic nystagmus (OKN). The spatially varying patterns may also vary temporally. In U.S. Pat. No. 5,539,482, issued Jul. 23, 1996 to James et al., additional systems and methods for diagnosing glaucoma using spatial as well as temporal variations in contrast patterns are disclosed. U.S. Pat. No. 5,912,723, issued Jun. 15, 1999 to Maddess, discloses systems and methods that use a plurality of spatially and temporally varying contrast patterns to improve the methods disclosed in the earlier patents. U.S. Pat. No. 6,315,414, issued Nov. 13, 2001 to Maddess et al., describes systems and methods for making a binocular assessment of possible damage to the optical nerve, optical radiations and white matter of the visual brain indicative of various neurological disorders by measuring responses to visual stimuli.

U.S. Pat. No. 6,068,377, issued May 30, 2000 to McKinnon et al., describes systems and methods for testing for glaucoma using a frequency doubling phenomenon produced by isoluminent color visual stimuli. The disclosure is similar to that of Maddess and co-workers, but uses different, preferably complementary, frequencies of light having the same luminosity as the visual probe signal.

U.S. Pat. Nos. 5,713,353 and 6,113,537 describe systems and methods for testing for blood glucose level using light patterns that vary in intensity, color, rate of flicker, spatial contrast, detail content and or speed. The approach described involves measuring the response of a person to one or more tight pattern variations and deducing a blood glucose level by comparing the data to calibration data.

Other disease conditions and their identification are described in a paper by S. Sokol, entitled “The visually evoked cortical potential in the optic nerve and visual pathway disorders,” which was published in Electrophysiological testing in diseases of the retina, optic nerve, and visual pathway, edited by G. A. Fishman, published by the American Academy of Ophthalmology, of San Francisco, in 1990, Volume 2, Pages 105-141. An article by Clark Tsai, entitled “Optic Nerve Head and Nerve Fiber Layer in Alzheimer\'s Disease,” which was published in Arch, of Ophthalmology. Vol. 107, February, 1991, states that large diameter neurons are damaged in Alzheimer\'s disease.

U.S. Pat. No. 5,474,081, issued Dec. 12, 1995 to Livingstone et al., describes systems and methods for determining magnocellular defect and dyslexia by presenting temporally and spatially varying patterns, and detecting visually evoked potentials (VEP) using an electrode assembly in contact with the subject being tested.

U.S. Pat. No. 6,129,682, issued Oct. 10, 2000 to Borchert et al., discloses systems and methods for non-invasively measuring intracranial pressure from measurements of an eye, using an imaging scan of the retina of an eye and a measurement of intraocular pressure. The intraocular pressure is measured by standard ocular tonometry, which is a procedure that generally involves contact with the eye. U.S. Pat. Nos. 5,830,139, 6,120,460, 6,123,668, 6,123,943, 6,312,393 and 6,423,001 describe various systems and methods that involve mechanical contact with an eye in order to perform various tests. Direct physical contact with an eye involves potential discomfort and risk of injury through inadvertent application of force or transfer of harmful chemical or biological material to the eye. Direct physical contact with an eye is also potentially threatening to some patients, especially those who are young or who may not fully understand the test that is being performed.

First Generation FDT Instrument

The Frequency Doubling Technique (hereinafter “FDT”) presents back-lit flashed images viewed on a fixed, flat shielded screen in front of a stationary subject. The FDT instrument is similar, but smaller, and the FDT test is substantially shorter in testing duration, as compared to a visual field instrument that tests peripheral and central vision. Visual field testing is standard in all offices providing comprehensive eye exams and treatment of eye disease. The FDT instrument uses sinusoidal grating targets of low spatial frequency (as opposed to simple dots of light in a traditional visual field test). The sinusoidal gratings are reversed (black to white, and white to black) at 25 Hz. The subject perceives the targets as small striped areas in either central or peripheral vision. As with traditional visual field testing, subjects are seated and have the chin and forehead positioned in a stabilizing rest support. Generally, subjects are tested monocularly. They fixate a target directly in front of them and respond by pushing a button each time they see an image flashed anywhere in their visual field. The instrument records and retests areas based on the subject\'s responses. A computer program operating on a processor calculates reliability based on fixation losses. The entire test takes less than two minutes per eye. The FDT does not require dilation of the subject\'s eyes. Therefore, it does not impair vision or the ability to function after the test is performed. The test causes no discomfort. The FDT has received approval from the Federal Drug Administration and has been in clinical use for over four years.

There is a need for systems and methods that will provide better information about a larger number of possible conditions using a single testing period, and that will disclose the initial levels of impairment at accuracies that are not presently attainable, while avoiding to the extent possible mechanical contact with the test subject, especially contact with the eye. There is also a need for systems and methods that can be used by non-specialist medical practitioners to screen and evaluate patients without the necessity to first involve a specialist practitioner. There is a need for relatively inexpensive, fast, easy-to-use, accurate screening apparatus and method for distinguishing between persons having various states of health, such as normal health, glaucoma, mild cognitive impairment (“MCI”) and mild Alzheimer\'s disease, moderate Alzheimer\'s disease and severe Alzheimer\'s disease.

In one aspect, the invention relates to an apparatus configured to differentiate a condition of normal health and at least one condition of impaired neurological health other than glaucoma. The apparatus comprises a Frequency Doubled Technology (“FTD”) apparatus configured to present to an eye of a medical subject of interest a time varying FTD optical pattern having a plurality of zones; a data collection apparatus configured to collect data from the medical subject based on a response of the medical subject to the time varying FTD optical pattern having a plurality of zones; and a data analysis apparatus configured to differentiate a condition of health of the medical subject based on the response of the medical subject.

In one embodiment, the response is based at least in part on a test time and the condition of health is a selected one of normal health, cognitive complaint, Mild Cognitive Impairment (“MCI”) and Alzheimer\'s Disease (“AD”). In one embodiment, the response is a response of the medical subject to different zones of the time varying FTD optical pattern having a plurality of zones and the condition of health is a selected one of normal health, cognitive complaint, Mild Cognitive Impairment (“MCI”) and Alzheimer\'s Disease (“AD”). In one embodiment, the response is a response of the medical subject to a combination of at least two variables selected from test time, point-wise loss, peripheral vs. central loss, pattern standard deviation, mean deviation, superior vs. inferior loss, left side vs. right side loss, left eye vs. right eye loss, and point-by-point parameters; and the condition of health is a selected one of normal health, cognitive complaint, Mild Cognitive Impairment (“MCI”), and Alzheimer\'s Disease (“AD”). In one embodiment, the data analysis apparatus is configured to compare the data collected by the data collection apparatus with data obtained by at least one of structural Magnetic Resonance Imaging, functional Magnetic Resonance Imaging, Diffusion Tensor Imaging, Positron Emissions Tomography, and Optical Coherence Tomography; and to provide a diagnosis of a condition of health selected from one of normal health and AD based on the comparison.

In one embodiment, the response is based at least in part on a test time and the condition of health is a selected one of normal health and head trauma. In one embodiment, the response is a response of the medical subject to different zones of the time varying FID optical pattern having a plurality of zones and the condition of health is a selected one of normal health and head trauma. In one embodiment, the response is a response of the medical subject to a combination of at least two variables selected from test time, point-wise loss, peripheral vs. central loss, pattern standard deviation, mean deviation, superior vs. inferior loss, left side vs. right side loss, left eye vs. right eye loss, and point-by-point parameters; and the condition of health is a selected one of normal health and head trauma. In one embodiment, the data analysis apparatus is configured to compare the data collected by the data collection apparatus with data obtained by at least one of structural Magnetic Resonance Imaging, functional Magnetic Resonance Imaging, Diffusion Tensor Imaging, Positron Emissions Tomography, and Optical Coherence Tomography; and to provide a diagnosis of a condition of health selected from one of normal health and head trauma based on the comparison.