Patent Application: US-201113167099-A

Abstract:
the present invention relates to an instrument and method for measuring the optical quality of an eye in a human subject . the instrument , which can be of either a single or double pass design and may include three - separate channels , permits real - time , simultaneous measurement of optical aberrations in the eye , retro - illumination of tear film to assess tear film stability , and scoring of psychophysical measures of visual performance . the simultaneous measurement of these parameters of optical quality and visual performance with the present instrument enables the operator to more accurately assess conditions and diseases of the eye , including dry eye disease .

Description:
one embodiment of the present invention is an instrument or optical system for more accurately measuring simultaneously and in real time metrics of optical quality obtained from double pass images , psychophysical measures of visual performance , and a retro - illumination image of the tear film . as shown in fig1 , a double - pass image of the optical aberrations in the human eye starts with a laser diode light source ( i . e ., 780 nm for the oqas ™) which is filtered and collimated at l 1 and ap 1 . the collimated light is then reflected off a beam splitter ( bs ) and passes through achromatic doublet lenses l 2 and l 3 with a focus corrector ( fc ) positioned between them . the fc can be moved to change the optical distance between l 2 and l 3 providing a means for spherical correction . the light path from the 780 nm laser diode to the point on the retina constitutes a single pass of the light through the optical system . the light reflecting off the retina then passes back through lenses l 3 and l 2 and l 4 where it is measured by a ccd camera ( c 1 ). the light returning to c 1 is collimated at aperture ap 2 . ap 2 can be set smaller then the eyes natural pupil to control for variability induced by the natural fluctuation of the iris as light is projected into the eye . in order to center the patient &# 39 ; s eye and measure pupil diameter a pupil image can be captured at c 2 . retroillumination ( ri ) images of the tear film are obtained simultaneously with the double - pass images using a infrared light emitting diode laser . as shown in fig1 , an ri image is captured using light from a 940 nm led , which is directed to the subject &# 39 ; s eye using band pass mirrors . the 940 nm light reflected by the subject &# 39 ; s eye passes through lens l 3 , after which it is directed and focused into a ccd camera c 2 for detection and image capture by a computer . in certain embodiments the instrument determines the location of a tear film break up using videokeratography . in another embodiment , the instrument determines the location of a tear film break up using the pentacam with fluorescein method . the subject maintains visualization of the hrp test target , displayed by a projector , at the detection threshold concurrent with the ri and double - pass imaging , so that visual performance is measured simultaneously with any changes in tear film quality and light scattering ( optical aberrations ). in certain embodiments , the instrument measures visual performance of the eye using a modified binary search ( mobs ) to establish a threshold . in one embodiment of the invention , synchronized computers are operably connected to cameras c 1 and c 2 and to the projector to simultaneously capture ri images and record optical aberrations at predefined intervals for a preset time period while the subject maintains visualization of the hrp test target at the detection threshold . in another embodiment a single computer may be used . the new instrument of the present invention can be produced from the oqas ™ ( optical quality analysis system ) developed by visiometrics s . l . ( terrassa , spain ), by replacing the pupil image camera of the oqas ™ with an iris camera ( e . g ., one capable of detecting infrared light ) and adding an infrared ( ir ) light source , as shown in fig1 . to obtain psychophysical measures of visual performance , the fixation target projector in the oqas ™ can be replaced by a micro - display which is controlled by a second computer . accordingly , in its final form the instrument of the present invention enables the operator to more accurately measure metrics of optical quality obtained from double pass images , psychophysical measures of visual performance , and a retro - illumination image of the tear film , simultaneously . moreover , because the optical aberrations and ri images are recorded at multiple intervals over time as tear film instability progresses , the measures can be directly related to the location of tear film break up on the cornea and its possible significance on the individual &# 39 ; s visual performance . alternatively , the instrument described herein for measuring dry eye disease can be constructed using off - the - shelf components as diagrammed in fig1 . preferably , the wavelength of light used to capture ri images is different from the wavelength of light used to measure optical aberrations . to obtain psychophysical measures of visual performance , the instrument of the present invention incorporates a third channel , which uses a micro - display controlled by a second computer . the micro - display projects images of test targets , such as hrp targets , which are reflected towards the subject &# 39 ; s eye so that the subject may visualize the images . in the case of hrp test stimuli , prior to starting a measurement , the subject is presented with a series of different sized hrp test targets ( fig3 ) to determine the subject &# 39 ; s detection threshold . the subject is then asked to maintain the hrp target at the detection threshold throughout the measurement period by adjusting a dimension of the target ( e . g ., the size of the ring target ) up or down using buttons connected to the computer controlling display the hrp target . in one embodiment of the present invention , double pass images , retro - illumination images of the tear film , and the subject &# 39 ; s threshold to a psychophysical stimulus are recorded every 0 . 5 seconds until a 19 . 5 - second capture sequence has been completed . thus , there will be 40 images showing optical quality evolution during the 19 . 5 second time period for both double pass and retro - illumination images . corresponding to these images are 40 psychophysical threshold estimates . to obtain a psychophysical threshold estimate , the subject &# 39 ; s threshold for visualizing a test image is determined before testing begins . once tear film testing starts the subject adjusts a feature or dimension of the test image ( e . g ., size , contrast , or spatial frequency ) to maintain its visibility at the threshold level throughout the 19 . 5 second time period . while visual stimuli varied along many dimensions ( e . g ., contrast , size , orientation , recognition and displacement ) could be envisioned in the device , it has not been recognized within the ded literature that most resolution targets are impractical as clinical diagnostic tools because they typically have two disparate thresholds : one for detection and one for resolution . for example , lambolt cs have been employed with the subject identifying the location of the open part of the “ c ” ( i . e ., up , down , left , or right ). this task requires a subject to first identify a target as seen ( detection threshold ) and then to identify its orientation ( resolution threshold ). each task has its own independent source of error and by definition the latter task has a minimum error rate determined by the number of possible choices : 25 % ( 1 in 4 directions ). the utilization of resolution targets and / or staircase threshold measurement techniques means that currently proposed technologies ( e . g ., lambolt c &# 39 ; s and visual acuity letters ) will poorly estimate the functional impact of tear film instability ( goto et al , 2002 ; johnson et al , 2002 ). the current invention can overcome these limitations by employing stimuli ( e . g ., hrp test targets ) which when spatially filtered bring detection and resolution thresholds into coincidence and / or by employing thresholding techniques which are robust to measurement error ( e . g ., modified binary search ( mobs )). high - pass spatial frequency filtering can be used to bring a target &# 39 ; s detection and resolution thresholds into coincidence ( howland et al , 1978 ). taking advantage of this principle , high - pass resolution perimetry ( hrp ) test targets ( fig3 ) were designed to have a single detection / resolution threshold . this is secondary to the design of the test target ( fig2 ) which consists of three concentric rings whose average luminance is equal to the background luminance of the screen . thus , optical distortion and / or neural under sampling will blur the concentric circles together resulting in an average luminance image equal to the background luminance of the screen ( i . e ., the rings are blurred into the background and become invisible ). hrp uses 14 different sized targets , stepped by 0 . 1 of a logarithmic unit ( 1 decibel , db ) to determine a subject &# 39 ; s detection threshold ( fig3 ). hrp was originally designed as a perimetric test for the detection of glaucomatous optic neuropathy ( frisen , 1987 ; sample et al , 1992 ; martinez et al , 1995 ). it has not been used for the detection of tear film instability secondary to dry eye disease . the application of this technology to ded has likely not occurred as tests designed for glaucomatous optic neuropathy are usually considered optimized to detect neural loss not optical quality . liu et al ( 2010 ) built a three channel optical system to simultaneously measure refractive aberrations ( shack - hartmann aberrometer ), 20 / 40 letter contrast sensitivity ( cs ), and tear - break up ( retro - illumination , ri ) ( fig3 ). the optics of this device are an adaptation of a maxwellian view ( westheimer , 1966 ; r . beer d et al , 2005 ). unfortunately , liu &# 39 ; s choice of a stimulus which varies contrast sensitivity ( cs ) is not optimal for detecting the impact of optical aberration upon functional outcomes . tear break up causes the contrast sensitivity function ( csf ) to shift slightly downward and considerably leftward ( i . e ., defocus shifts the descending limb leftward ) ( see montés - micó et al , 2005 ). the left end of the csf descends rapidly which means that large changes in contrast produce small shifts in the highest spatial frequency ( sf ) which the optical system can resolve . conversely small shifts in optical quality will cause significant losses in the highest sf content resolved by the optical system . thus , the ideal psychophysical stimulus for relating functional outcomes to tear stability and optical aberrations should vary size and / or high spatial frequency content not contrast . the previously proposed technique of utilizing test stimuli , such as high - pass resolution perimetry ( hrp ) test targets , which when high - pass spatial frequency filtered blend into the background , uniquely satisfy these requirements . with the present instrument , double pass images , retro - illumination images of the tear film , and the subject &# 39 ; s threshold to a psychophysical stimulus are recorded every 0 . 5 seconds until a 19 . 5 - second capture sequence has been completed . thus , there will be 40 images showing optical quality evolution during the 19 . 5 second time period for both double pass and retro - illumination images . corresponding to these images are 40 psychophysical threshold estimates . to obtain a psychophysical threshold estimate the subject &# 39 ; s threshold for visualizing a test image is determined before testing begins . once tear film testing starts the subject adjusts a dimension of the test image ( e . g ., size , contrast , or spatial frequency ) to maintain its visibility at the threshold level throughout the 19 . 5 second time period . the new instrument described herein differs from previous single channel maxwellian view instruments such as the oqas ™ system in several significant ways : 1 ) it incorporates three channels ; 2 ) it can simultaneously measure tear break - up both objectively and subjectively ; 3 ) it elucidates the spatial relationship between focal tear film break up ( i . e ., retro - illumination ) and both optical aberrations and psychophysical performance . thus , this instrument provides an understanding of how optical aberrations relate to functional performance ( e . g ., visual acuity ) and focal disturbances of the tear film throughout a blink - free interval . furthermore , the use of different sized hrp test targets with the present instrument makes it possible to detect tear film instability secondary to dry eye disease and determine a subject &# 39 ; s detection threshold . in its final form as described above , the instrument uses a three channel optical system which may simultaneously and non - invasively measure refractive aberrations ( shack - hartmann aberrometer and / or double - pass optical method ), psychophysical performance , and tear break - up ( retro - illumination , ri ). this enables a causal relationship between tear film thickness , optical aberrations and subsequent retinal image quality to be established and significantly reduces testing time and physician / patient burden . the new device will also significantly increase the reliability of the observed measurements as measurements of objective visual function and tear stability will occur simultaneously and within a single blink - interval ( usually less than 10 seconds in patients with ded ). this information is currently approximated by completing subjective questionnaires and tear breakup with fuorescein or a non - invasive tear breakup by videokeratography . together these tests take over 30 minutes of time to complete . a 63 year old female patient tells her ophthalmologist about excess tearing , burning eyes , and intermittent blurred vision . the ophthalmologist conducts an ocular surface exam which includes surface staining assessment with fuorescein / yellow filter , a schirmer i test without anesthetic , and lid and meibomian morphology . the patient is then referred to a technician who utilizes the present invention to simultaneously and non - invasively assess tear film stability and its impact upon functional vision . thus , a full exam satisfying all of the dews ( dry eye workshop ) recommendations is achieved with two the of critical components ( i . e ., tear film stability and functional vision ) completed by a trained technician . the ophthalmologist determines the patient has ded and provides treatment . suspected ded patients present to an optometrist complaints of excess tearing , burning eyes , and / or intermittent blurred vision . the optometrist utilizes the present invention to simultaneously and non - invasively assess tear film stability and its impact upon functional vision . the optometrist also utilizes a third channel ( i . e ., shack - hartmann aberrometer and / or double - pass optical method ) to screen non - native speaking patients and / or an individual who could not perform the psychophysical task by comparing the shack - hartmann aberrometer and / or double - pass optical method of measuring aberrations to the results from a retro - illumination image of the tear film . if tear film instability is identified along with significant impairments in functional vision the patient is referred to an ophthalmologist who conducts an ocular surface exam and provides treatment accordingly . in a clinical trial testing a treatment for ded , the present invention is used to determine effectiveness of the treatment . high - pass resolution perimetry ( hrp ) test targets are substituted with snellen visual acuity optotypes ( e . g ., letters , “ e ” s , or symbols ) which are varied in size not contrast . this allows direct extrapolation of the test results to established metrics of visual acuity , logmar visual acuity , facilitating a clear understanding of the clinical significance of any observed changes in tear break - up . 1 . albarran c , pons a m , lorente a , montes - mico r , artigas j m . influence of the tear film on optical quality of the eye . contact lens ant eye . 1997 ; 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