Classifications

• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01B—MEASURING LENGTH, THICKNESS OR SIMILAR LINEAR DIMENSIONS; MEASURING ANGLES; MEASURING AREAS; MEASURING IRREGULARITIES OF SURFACES OR CONTOURS
  • G01B11/00—Measuring arrangements characterised by the use of optical techniques
  • G01B11/02—Measuring arrangements characterised by the use of optical techniques for measuring length, width or thickness
  • G01B11/06—Measuring arrangements characterised by the use of optical techniques for measuring length, width or thickness for measuring thickness ; e.g. of sheet material
  • G01B11/0616—Measuring arrangements characterised by the use of optical techniques for measuring length, width or thickness for measuring thickness ; e.g. of sheet material of coating
  • G01B11/0675—Measuring arrangements characterised by the use of optical techniques for measuring length, width or thickness for measuring thickness ; e.g. of sheet material of coating using interferometry
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
  • A61B3/00—Apparatus for testing the eyes; Instruments for examining the eyes
  • A61B3/10—Objective types, i.e. instruments for examining the eyes independent of the patients' perceptions or reactions
  • A61B3/101—Objective types, i.e. instruments for examining the eyes independent of the patients' perceptions or reactions for examining the tear film

Definitions

• This invention relates generally to the field of measurement of the tear film thickness on the precorneal surface of the eye and more particularly, to the measurement of the thickness of the outermost layer of the tear film, i.e., the lipid layer.
• the human precorneal tear film is comprised of three primary layers, each of which serves a specific function.
• the innermost layer of the precorneal tear film provides a protective environment for the superficial epithelial cells of the cornea and helps protect against microbes and foreign bodies.
• the outer surface of the precorneal tear film is the primary refracting surface of the eye. Its surface tension helps to smooth this surface, thus improving the optical quality of the image ultimately impacting the retina. Additionally, the precorneal tear film provides a lubricating function during blinking. These structures are often disrupted in dry eye conditions, which are some of the most common ophthalmic disorders seen by eye-care practitioners.
• Dry eye disorders and/or disease can lead to premature breakup of the tear film after a blink, leading to damage of the superficial epithelium which may result in discomfort and be manifested as optical blur.
• the ability of a patient to wear contact lenses is a direct function of the quality and quantity of the tear film, and dry eye disorders and/or disease therefore has a significant impact on contact lens wear parameters.
• the precorneal tear film is comprised of an inner mucin layer, a middle aqueous layer, and an outermost thin lipid layer.
• Various treatments are used in an attempt to alleviate dry eye symptoms. For example, it has been proposed to treat certain dry eye conditions by the application of heat and pressure to unclog meibomian glands, or with pharmaceutical methods to unclog meibomian gland and to stimulate tear production.
• lipid layer thickness values Following calibration with Eastman Kodak color reference standards (Wratten filters), the static and dynamic appearance of the lipid layer was observed before and after blinking. During the observation period, the subject was instructed to blink naturally while gazing at a fixation target. For purposes of quantization and standardization, a specific region of the tear film was designated for analysis. This area encompassed a zone approximately one mm above the lower meniscus to slightly below the inferior pupillary margin, averaging 7-8 mm wide and 2.5 mm in height. The dominant color of the specularly reflected light within this designated area was used as the basis for assigning lipid layer thickness values.
• Thickness values were assigned to specific colors on the basis of prior work on tear film lipid layer interference colors (McDonald, 1969; Norn.; 1979; Guilon, 1982; Hamano et al., 1982) and are summarized in Table 1. To confirm the lipid layer thickness values assigned to each subject's tear film lipid layer, recordings were independently graded by two observers masked as to subject identity. (Korb, DR, Baron DF, Herman JP, et al., Tear Film Lipid Layer Thickness as a Function of Blinking, Cornea
• Doane discloses a Method and Device for in Vivo Wetting Determinations wherein a contact lens is illuminated with coherent light and the pre-lens tear film is imaged in such a way as to form an interference pattern. The image formed thereby is recorded and the tear film thickness is determined by correlating the interference bands of the recorded image.
• a coherent light source and a camera are focused at the pre-lens film to image specularly reflected light from the front and rear surfaces of the tear film.
• a film motion analyzer provides numerical coordinates of interference bands, and a microprocessor analyses the coordinates to provide a quantitative measure of lens position or wetting characteristics. Again, while knowledge of the tear film thickness covering the contact lens surface may be useful in the context of contact lens fitting, the Doane apparatus does not specifically measure lipid layer thickness on the natural eye.
• Tearscope Plus manufactured by Keeler Instruments Inc., of Broomall, PA and Berkshire, UK. More specifically, the Tearscope is a hand-held or slit lamp mounted device that comprises a tubular housing which contains a coaxially mounted cylindrical light source. The interior bore of the housing is covered with a cylindrical diffuser plate that diffuses the light.
• the eye- care practitioner places one end of the tube proximate the patient's eye thus illuminating the whole eye, including the pupil, and observes the interference patterns on the pupil surface through the opposite end of the tube, The color of the interference pattern generated by blinking is then correlated to tear film thickness.
• the Tearscope is not without its inherent drawbacks and deficiencies as the process by which the eye is illuminated and the measurement is made introduces error which is diagnostically unacceptable.
• the proximity of the illuminator to the eye surface when combined with the light intensity required to obtain a viewable interference pattern can cause reflex tearing.
• the illumination system employed illuminates the entire eye, including the pupil.
• light from the Tearscope is directed on to the retinal surface which, in turn causes a proprioceptive response which also skews measurement accuracy.
• Another object of the present invention is to provide a method and apparatus that allows the accurate measurement of the thickness of the lipid layer component of the precorneal tear film.
• a further object of the present invention is to provide a method and apparatus wherein the lipid layer thickness of the precorneal tear film may be measured without the introduction of reflex tearing.
• a still further object of the present invention is to provide a method and apparatus that enhances contract and thereby the observability and measurablity of the lipid layer thickness of the precorneal tear film.
• Yet another object of the present invention is to provide a method and apparatus for measuring the lipid layer thickness of the precorneal tear film using a low level of light in order to minimize tear film evaporation that can alter the measurement.
• the invention comprises an apparatus for measuring the thickness of the lipid layer component of the precorneal tear film on the surface of an eye after distribution of the lipid layer subsequent to blinking.
• An illuminator directs light to the lipid layer of a patient's eye.
• a means for observing the specularly reflected light rays is provided.
• the illuminator is a broad spectrum, large area lambertian light source covering the visible region, the rays of which are specularly reflected from the lipid layer and undergo constructive and destructive interference in the lipid layer.
• a collector such as a camera or slit lamp may be provided to collect and focus the specularly reflected light such that the interference patterns on the tear film lipid layer are observable.
• the collector also produces an output signal representative of the specularly reflected light which is suitable for further analysis, such as projection on to a high resolution video monitor or analysis by or storage in a computer.
• the interference patterns of the specularly reflected light may be directly observed by the clinician and recorded.
• the patient's head may be positioned on an observation platform, for example, a slit lamp stand, when the illuminator directs light to the lipid layer of the patient's eye.
• the illuminator is sized to show the interference pattern of the lipid layer over the whole eye, (termed herein the "whole eye illuminator"), with the provision that the intensity of the light entering the pupil and striking the retina are below the threshold at which appreciable measurement error is introduced, i.e., the reflex tear and proprioceptive responses are not activated.
• Observation of the interference pattern in the preferred embodiment is through an opening in the illuminator.
• the illuminator is sized to show the interference pattern of the lipid layer below the pupil, (termed herein the "half eye illuminator"), such that the intensity of the light entering the pupil is extremely low, thus avoiding the introduction of virtually all system-induced inaccuracy. Observation of the interference pattern in this second embodiment is from above the illuminator.
• Figure 1 is a side view of the tear film analyzer according to the present invention mounted to a stand with a patient positioned for viewing of interference fringes on the lipid layer of the eye.
• the illuminator portion is shown as a vertical cross section through the center.
• Figure 2 is a plan view of the tear film analyzer according to the present invention mounted to a stand with a patient positioned for viewing of interference fringes on the lipid layer of the eye.
• Figure 3a is a side view of a second embodiment of the tear film analyzer according to the present invention mounted to a stand with a patient positioned for viewing of interference fringes on the lipid layer of the eye.
• the illuminator portion is shown as a vertical cross section through the center.
• Figure 3b is a side view of the second embodiment of the tear film analyzer according to the present invention mounted to a stand and tilted with a patient positioned for viewing of interference fringes on the lipid layer of the eye.
• the illuminator portion is shown as a vertical cross section through the center.
• Figure 4a is a plan view of the second embodiment of the tear film analyzer according to the present invention mounted to a stand with a patient positioned for viewing of interference fringes on the lipid layer of the eye.
• Figure 4b is a plan view of the second embodiment of the tear film analyzer according to the present invention mounted to a stand and tilted with a patient positioned for view of interference fringes on the lipid layer of the eye.
• Figure 5a is a plan view of the second embodiment of the tear film analyzer according to the present invention illustrating the illuminator surface that produces the outer edges of the viewable area of interference fringes.
• Figure 5b is a side view of the second embodiment of the tear film analyzer according to the present invention illustrating the illuminator surface positioned below the plane of the pupil and tilted at an angle and showing the outer edges of the viewable area of interference fringes.
• Figure 5c is a side view of the second embodiment of the tear film analyzer according to the present invention illustrating the illuminator surface vertically positioned below the plane of the pupil and showing the outer edges of the viewable area of interference fringes.
• Figure 6 is a perspective view, partially exploded, of the full eye illuminator according to the present invention.
• Figure 7 is a plan view, sectioned horizontally through the center of the viewing hole of the full eye illuminator according to the present invention.
• Figure 8 is an end view, sectioned vertically through the center of the full eye illuminator according to the present invention.
• Figure 9 is a perspective view, partially exploded of the half eye illuminator according to the present invention.
• Figure 10 is a plan view with the top removed of the half eye illuminator according to the present invention.
• Figure 1 1 is an end view, sectioned vertically through the center of the half eye illuminator according to the present invention.
• Figure 12 is a front view of the surface of an eye and illustrating schematically the area defined by the extreme lambertion rays wherein interference patterns are viewable.
• the apparatus broadly comprises an illumination means 100 and a means for observing the specularly reflected light 200.
• a second embodiment best shown in figures 3a, 3b, 5a-5c and 9-1 1 , referred to herein as the "half eye” illuminator is shown.
• the mode of operation of the two embodiments is substantially identical and they will therefore be described together using the same reference numerals and where differences between the embodiments occur, they will be discussed.
• the illumination means 100 for directing light to the lipid layer of the patient's eye comprises a large area broad spectrum light source covering the visible region and being a lambertian emitter adapted to be positioned in front of the eye on a stand 300.
• the terms "lambertion surface” and “lambertian emitter” are defined to be a light emitter having equal intensity in all directions.
• the light source comprises a large surface area emitter, arranged such that rays emitted from the emitter are specularly reflected from the lipid layer and undergo constructive and destructive interference in the lipid layer. An image of this surface is the backdrop over which the interference image is seen and it should be as spatially uniform as possible.
• the illumination means 100 illuminates a large area of the face which creates a 2.5mm high by 5mm long viewable area centered beneath the pupil 310 (see figure 12) which is adequate for lipid layer thickness determination and correlation to dry eye.
• viewable area it is meant the active area that satisfies the criteria for viewing interferences fringes; i.e., approximately 2.5 mm x 7 mm for the half eye illuminator.
• Full-eye illumination, excluding the pupil area, reveals additional information about the whole eye pattern of lipid distribution.
• the geometry of the illuminator 100 can be most easily understood by starting from the camera lens and proceeding forward to the eye and then to the illuminator.
• 0 2 .
• the present invention it is necessary to determine only the extreme rays (the ones at the outermost boundary of the desired viewing area) to define the area of the illuminator. Since the surface of that portion of the eye to be examined is approximately spherical, a line drawn from the camera lens (or the observer's eye) to the edge of the viewing area on the observed eye will reflect at the same angle on the other side of the line normal to the eye surface at the point of intersection of the line with the eye. When the half eye illuminator used, it may be tilted to better accommodate the nose and illuminate a larger area of the inferior lipid layer.
• the illumination means 100 is a broad spectrum light source covering the visible region between about 400 nm to about 700 nm.
• white Light Emitting Diodes (“LEDs”) 120 were used that have a 50° forward projection angle, 25OOmcd typical intensity, and 5mm diameter (part number NSPW51 OCS, available from Nichia Corporation, Wixom, MI).
• LEDs white Light Emitting Diodes
• the light emitting array platform 130 (Figs. 6, 7) into which the LEDs are mounted had a curved surface, subtending an arc of approximately 130° from the optical axis of the eye (see Fig 5a).
• a housing is formed around the LED array platform 130 by a pair of side panels 135, bottom and top panels 140, rear panel 145 and the diffuser means or diffuser 150.
• the respective diffuser 150, LED platform 130, and rear panel 145 are flexible and fit within grooves 147 located in the top and bottom panels 140 and the end pieces 135. The entire assembly is snapped together and the side panels 135 are then screwed to top and bottom panels 140.
• illumination means 100 illustrated in the figures is curved or arcuate and has a radius of 7.620 inches from the center of the eye under examination, it could be flat as long as it subtends 130° around the eye.
• a curved surface is more efficient in doing this, as the geometry yields a smaller device which is easier for the practitioner to use in a clinical setting.
• the total power radiated from the illuminator 100 must be kept to a minimum to prevent accelerated tear evaporation.
• air currents generated by heating or cooling systems can also cause excess evaporation and must be minimized (preferably eliminated) to maintain measurement accuracy.
• the brightness, or intensity, measured in ⁇ W/mm 2 entering the pupil can cause reflex tearing, squinting, and other visual discomforts, all of which affect measurement accuracy.
• the curved lambertian emitter includes a centrally positioned hole defining an opening 160 through which the means for collecting and focusing the specularly reflected light, i.e., a camera, eye, or other lens 200, is positioned.
• the opening 160 in the center substantially prevents direct illumination from entering the pupil of the test eye. While less than optimal, the opening 160 could be located in other parts of the illuminator.
• the other eye has the full light intensity entering the pupil. If the illumination intensity is low enough, the exposed eye does not react.
• the exposed eye may also be occluded with a mask, or the illuminator may be segmented so that parts of the surface are not illuminated.
• the half-eye illuminator stops below the centerline of the eye and does not directly illuminate either pupil or stated otherwise, light rays can only enter the pupil obliquely and do not impinge on the retina.
• the current full-eye illuminator has a brightness or illumination intensity of between about 3 ⁇ W/mm 2 and 15 ⁇ W/mm 2 with about 4.5 ⁇ W/mm 2 at the surface of the illuminator being preferred, which is held 1-2 inches from the eye.
• the total radiated power is less than I W and preferably no more than 40OmW. Brightness above about 6 ⁇ W/mm 2 becomes uncomfortable to the second eye if it enters the pupil so as to impinge directly on the retina.
• the front surface of the illuminator is the lambertian emitter, i.e., all points on the extended illuminator surface are lambertian emitters, and comprises a flexible white translucent acrylic plastic sheet 150 approximately 1/16 inch thick that serves the function of diffusing the light emitted from a plurality of LED point sources and transforming them into the uniform Lambertian emitter.
• the means for collecting and for focusing the specularly reflected light such as a high sensitivity color camera 200 should be employed.
• the video camera, slit lamp or other observation apparatus 200 is positioned in opening 160 and is also mounted on stand 300 as shown in figure 2 or in the case of the half eye illuminator positioned above the emitter as per figures 3a and 3b.
• Detailed visualization of the image patterns requires a means for collecting the specularly reflected light and for focusing the specularly reflected light such that the interference patterns from the lipid layer are observable.
• Good digital imaging requires a CCD video camera having a resolution of up to 1280 x 1024 pixels and at least 15 Hz frame rate to show the progression of lipid interference patterns as they spread across the eye.
• the AVT Dolphin 145C, 2/3 inch, CCD camera with 6.45 ⁇ m 2 pixels meets the requirements and outputs a signal representative thereof which may serve as the input signal to any one of a number of devices such as a video monitor (preferably high resolution) or a computer for analysis and/or archiving purposes.
• the lens system employed in the instant tear film analyzer images a 15 - 40mm dimension in the sample plane (the eye) onto the active area of the CCD detector (e.g. ⁇ 10mm horizontal dimension for a 2/3 in. CCD).
• the lens f-number should be as low as practical to capture maximum light and minimize the illumination power needed for a good image.
• the lens chosen for the half-eye and full-eye systems is the Navitar Zoom 7000 close focus zoom lens for 2/3in. format CCDs. At lower magnification (25-40mm field of view), the eye and lids can be examined to observe the relationship of the blink to the lipid layer thickness. A more detailed analysis of the lipid layer can be obtained with a slightly higher magnification showing a 15- 25mm field of view.
• the lipid layer thickness is not uniform and is classified on the basis of the most dominant color present in the interference pattern. It is believed that the lipid layer for most individuals cannot exceed 180 nm, and since thicker lipid layers provide better protection from evaporation than thinner lipid layers, thicker lipid layers provide greater protection against the development of dry eye states. Thinner lipid layers are associated with dry eye states and dry eye symptoms, particularly if the lipid layer thickness is less than 75nm.
• the present system displays the interference patterns from white light incident on the lipid layer film.
• the relation between the colors of the interference pattern and the lipid layer thickness (LLT) are shown in Table 1.
• brown can be obtained in an additive process by mixing small intensities of red and green, or orange and blue, basically the opposite ends of the visible light spectrum. Alternatively, brown can be obtained in a subtractive process by filtering out the central yellow-green colors from the white spectrum, leaving a blue- orange mix.
• the thickness of the lipid layer on the eye is much smaller than all the wavelengths of visible light. Therefore, full wavelength interference patterns are believed not to be possible.
• the intensity in the interference pattern decreases rapidly as n increases and the ability to differentiate weak interference patterns from the background decreases accordingly.
• the present invention demonstrates the results of subtractive colors, where subtracting the blue end from white light leaves a reddish tint, subtracting the center (yellow-green) from the spectrum leaves a brownish tint, and subtracting orange-red leaves a blue tint. Because all the interference patterns are fractional wavelengths, and therefore relatively weak in intensity, the images are not strongly saturated. Image enhancement techniques therefore assume a higher importance for good visibility. Film thickness below about 90nm can be determined by gray scale analysis.
• the term "real time" is defined as data transfer, storage and retrieval at a rate required for image generation that the observer requires for a subjectively satisfactory viewing experience.
• a minimum of about 15 frames per second is satisfactory for seamless motion perception.
• the camera can create 1.4-3.9MB images at 15 per second, or 21-57MB/sec which must be processed by the computer for storage, display, or computation.
• one minute of recording requires 1.26-3.42GB of storage.
• the data from the camera must be streamed directly to a storage system sized to meet the anticipated volume of data. For example, 500 GB of storage could record 147-397 tests of one minute duration.
• Various forms of data management could be applied to reduce the storage requirements, including image size, compression, and minimizing recording time adequate to good diagnostics.
• the software to operate the camera, capture the images, store and retrieve image files, and execute chosen calculations on the data is critical to the success of the system.
• Relevant specifications are:
• the mechanical system consists of components to position the patient's head, position the illuminator and camera, focus the camera, and switch position between eyes.
• a movable frame positions the camera and illuminator opposite the patient's face.
• the illuminator and camera move together in a gross manner, but the illuminator has an independent X and rotational motions for accommodating different facial geometries.
• Switching from eye to eye requires moving the whole camera/illuminator frame away from the patients face (X motion) and horizontally to line up with the second eye (Y motion).
• Focusing the camera requires fine control of X motion, and vertical Z motion is required to accommodate differences in patient eye positions.
• a classical slit lamp biomicroscope stand incorporates most of these motions, and have added angular motions not needed in the present system.
• Figuresl, 2, 3a-3c illustrate the full-eye system.
• a typical examination session proceeds as follows: Presets: The vertical relationship between the camera and the illuminator is set. For a half- eye illuminator, the camera position is just enough higher than the illuminator top edge that the image contains no edge effects. When using the full-eye illuminator, the camera is positioned coaxially with the hole through the illuminator. The camera/illuminator position should not need adjusting thereafter.
• the patient is seated and asked to place their chin on the chin rest.
• the chin rest is adjusted (Z axis) for the comfort of the patient.
• the patient is asked to hold their forehead against the forehead rest.
• the frame holding the camera & illumination is positioned on the axis of the first eye and brought close enough for rough focus on the skin.
• the frame is adjusted for vertical and horizontal centering, and then moved forward for fine focusing.
• the illuminator is adjusted forward and back, and rotated for best illumination of the eye. Repeat fine focus as necessary. The patient is asked to look directly at the center or top center of the camera lens. Instructions are given to the patient for blinking regimens by the diagnostician.
• the images are viewed and recorded as desired.
• the frame may be pulled away from the patient (to clear the nose) and moved horizontally to the next eye. Steps 2.-5 are repeated.
• the system could be fully motorized and operated in manual, semi-autonomous, or autonomous modes, depending upon the sophistication of the control software.
• a fully automatic system would adjust the mechanical stand, focus the camera, record the motion of the lipid film, calculate various measurements of the film structure, report an assessment of the quality of the lipid film, and record the data in the patient's record file.

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• 2007
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