Method and device for analysis of ocular tear film dynamics

Abstract

Methods and devices are provided for analyzing ocular tear film dynamics via laser ray tracing for information acquisition on changing optical properties caused by the tear film dynamics. Information is acquired during after-blink measurement sessions of laser ray tracing and reconstruction of a two-dimensional distribution of the position and the spread of the laser spot projection on the retina.

Description

[0001] METHOD AND DEVICE FOR ANALYSIS OF OCULAR TEAR FILM DYNAMICS

[0002] Cross-Reference to Related Applications

[0003] This international patent application claims benefit of priority under 35 U.S.C. §119(e) of provisional patent application U.S. Serial No. 63 / 573,740, filed April 3, 2024, the entirety of which is hereby incorporated in its entirety.

[0004] BACKGROUND OF THE INVENTION

[0005] Field of the Invention

[0006] The present invention relates generally to the fields of ophthalmic instruments that are used to examine human vision. More specifically, the present invention relates to ophthalmic examination instruments that measure parameters of the ocular tear film dynamics for diagnosing the dry eye condition.

[0007] Description of the Related Art

[0008] Diagnosing the dry eye condition by measuring the stability of the tear film is essential for assessing the health of the ocular surface. The tear film is in a micrometer range of thickness and contains a lipid layer and an underlying muco-aqueous layer. In a healthy eye, a blink spreads the tear film evenly across the ocular surface. It is particularly important when evaluating the outcomes of any procedure associated with disruption of the tear film like surgery or contact lens intolerance. Known are invasive and non-invasive techniques for testing the tear film break-up times. All of them are based on the specificity of the tear film multilayered transparent structure and its dynamic features.

[0009] The fluorescein tear film break-up time test is one of the most common tests for dry eye syndrome (1 ). The test involves application of fluorescein sodium drops to the ocular surface and subsequent measurement of the time required for the first random dark spot to appear. The dark spot is an area of increased concentration of fluorescein caused by tear film evaporation. This area appears as a dark color under cobalt light excitation. The dark area is the fluorescein tear film break-up area commonly caused by a poor-quality tear film and is a sign of an unstable tear film structure.

[0010] A thin lipid layer, as a cover of the tear film, helps to reduce evaporation of the underlying aqueous layer. According to one of the theories of the tear film dynamics, an inner mucus layer is spread onto the corneal surface by blink action, another view of this layer is that it consists of membrane-bound mucin molecules that form the glycocalyx. To have a look at the turn-over of lipids in the tear film, the fluorescence can be used of injected nano-size particles (quantum dots) designed to interact specifically with the lipid layer (2). They emit discrete wavelengths of light due to quantum size effects. Their emission is both very bright and very stable. Silicon based quantum dots doped with transition metals such as scandium and copper are the last achievement in the field.

[0011] As mentioned above, one of the mechanisms having the influence on the break-up is the evaporation over an extended area making the tear film in this area thinner between blinks. Since it is a thermal process, it can be evaluated with the thermosensitive imaging (3).

[0012] The tear film and its layers are so thin, that the light interferometry can be applied for their diagnostics (4). The known approaches are based on parameter measurement of fringes that are dependent on thickness, angle, and wavelength. A combination of these approaches allows the evaluation of the role of both tear film flow and evaporation in tear film thinning and breakup.

[0013] Several variants were proposed based on variability of the shape of the tear film surface. One of them exploits the calculation of the autocorrelation function of a pair of adjacent images from the video camera captures of the illuminated tear film surface. Analysis of the time sequence of calculated autocorrelation functions describes the post-blink dynamics of the tear film (5). Another version adds a projection of an additional structure on the precornea surface. These can be a speckle structure of the coherent light, a regular mesh structure, but the widest attention is paid to the regular concentric structure of Placido disks (6). A variety of processing approaches were studied, including analysis of time sequencies of image autocorrelation values, sectorial spatial frequency analysis, with image preprocessing, like edge filtering, line shape smoothing, etc.

[0014] Since the tear film surface is a one that determines the total refraction of the eye, variations of its features can be derived from the variations of the wave front, induced by the dynamics of the tear film shape and thickness (7). The effect of the tear film on the transmitted wavefront through the optics of the eye can be described by the root mean square error of the wavefront over time.

[0015] Still another approach to measure the dynamics of the tear film consists in measuring the aberrations of the total eye under the suggestion that their dynamics is caused by the refraction variations due to the tear film. The higher order aberrations are here the main descriptors (8). Unfortunately, the non-stop accommodation adjustments and the saccades are overlaid on the time variations of the tear film refraction dynamics masking the features necessary for diagnostics. It should be noted at this point that the mathematical procedure based on minimization of the root mean square errors of approximation of the reconstructed wave front to the raw data results in smoothed mapping (2D interpretation), in which the principal features contained in the higher spatial frequencies, are washed out. To overcome the difficulties of diagnostic, a combination of the corneal topography, the aberrometry of the total eye, and the profile measurements with optical coherence tomography was proposed (9). The same as with the separate sources of information, the fluctuations due to accommodation processes, eye saccade movements and mathematical specificity of data smoothing with Zernike polynomials are not neutralized or diminished. None of the described solutions outputs a reliable diagnosing of the dry eye disease with suppressed influence of the interfering factors of eye motoric physiology and specific mathematical processing. Thus, there is a need in the art with minimized trade-offs of the technologies based on the wave front measurements The present invention fulfills this longstanding need and desire in the art.

[0016] SUMMARY OF THE INVENTION

[0017] Analysis of the ocular tear film dynamics is based on after-blink measurement sessions of ray tracing with specified time intervals between sessions. Each session of ray tracing comprises sequential-in-time laser probing of the eye in a set of points within the aperture of the eye, and detection of the laser beam projections on the retina. The eye is oriented along the optical axis, and the probing of the eye is provided with the instrumentally compensated ametropia of the eye, where a configuration of the set of points is the same in each session of probing, where each point of probing represents the same point of the eye aperture in each session.

[0018] The ray tracing information is compared between a current session and a reference session, where the reference session is any previous-in-time session, preferably initial afterblink session. The ray tracing information comprises a width of a registered light intensity profile of laser beam projection on the retina representing a point spread function for each probing point, where the width is measured at a certain level of the light intensity profile.

[0019] In another implementation, the ray tracing information comprises a total intensity of the registered profile of laser beam projection on the retina in each probing point, where the total intensity is normalized relatively the maximal value of the total intensity among all probing points of the current session.

[0020] Still in another implementation, the ray tracing information comprises a difference between positions of laser beam projections on the retina of the current session and of a reference session, where the reference session is any previous-in-time session, preferably initial after-blink session. The difference between positions of laser beam projections on the retina is calculated after compensation of accommodative and saccadic movements of the eye. Compensation of accommodative and saccadic movements of the eye is provided in several steps: (a) geometrical centers of the to be compared sets of coordinates are calculated and a translation value is calculated that is the distance between the geometrical centers; (b) mean values of radial distances from the geometrical centers of all points in each of the to be compared sets of coordinates are calculated, a scaling value is calculated that is the ratio of the mean values of radial distances; (c) affine transformation of the set of coordinates of each session is made regarding a reference session based on the calculated translation and scaling values.

[0021] A two-dimensional distribution is reconstructed of changing optical properties of the eye caused by the tear film dynamics and displayed as a map of tear film dynamics.

[0022] A device for analysis of the ocular tear film dynamics, implementing the features of the proposed method, comprises a video camera with a first objective lens, conjugating the video camera with the pupil of the eye, optometric target with a second objective lens in configuration enabling the conjugation of the optometric target with the retina of the eye, a laser with an acousto-optical scanner and a collimating lens in the ray tracing configuration on the path into the eye, and a profile sensor with a third objective lens on the path from the eye, a synchronizer, and a processing unit connected through the bus to the video camera, optometric target, laser, acousto-optical deflector and profile sensor, where the processing unit has a display at its output.

[0023] On the path to the eye after the collimating lens, a first fluidic lens and a telescope lens are installed in configuration enabling the compensation of the defocus component of eye ametropia for the laser beams that probe the eye. On the path from the eye, after the telescope lens, a second fluidic lens is installed in configuration enabling the compensation of the defocus component of eye ametropia for the images of the retinal projections. Optical paths to the eye and from the eye to video camera, to profile sensor and to optometric target are split by a first, a second and a third beam splitters.

[0024] The processing unit comprises the following blocks: 1 ) a memory block configured to accept the data of all after-blink sessions from the profile sensor, 2) a translation block connected with its inputs to the profile sensor and to the memory block, 3) a scaling block connected with its inputs to the translation block and to the memory block, 4) a coordinate variation block connected with its inputs to the scaling block and to the memory block, 5) a coordinate variation mapping block connected with its input to the coordinate variation block, 6) a projection parameter block connected with its inputs to the profile sensor and to the memory block, 7) a projection parameter mapping block connected with its input to the projection parameter block, and 8) a dynamics mapping block connected with its inputs to the projection parameter mapping block and to the coordinate variation mapping block, its output connected to the display.

[0025] BRIEF DESCRIPTION OF THE DRAWINGS

[0026] FIG. 1 presents the functional schematic of the device implementing the proposed method. The laser beam from laser 1 hits the eye 8, the back scattered light is detected by profile sensor 14. Processing unit 17 analyzes variations of the position, width and amplitude of the signal from profile sensor 14. Video camera 10 assists the process of eye positioning. Optometric target 15 provides optical conjugation using electrically controlled fluidic lenses 4 and 11.

[0027] FIG. 2 illustrates projection of a thin laser beam in the eye. The beam crosses the pupil of the eye in the point with coordinates Xi, Y,, and hits the retina in the point x,, y. The beam enters the eye in the plane of optical axis coinciding with Z axis. The point x,, y, may not be in the plane of hitting the eye (where the optical axis and the hitting laser beam are).

[0028] FIG. 3 compares the signals from the profile sensor 14 (FIG. 1 ) in the same point of the pupil plane in the session “1 second after blink” and in the session “7 seconds after blink”. The positions of signal maxima xmax(7s) vs xmax(is), signal widths w7svs wis, and signal amplitudes h75vs / ?iscan differ in the process of tear film dynamics.

[0029] FIG. 4 shows a typical set of points (a pattern) in the pupil plane, in which the laser beam crosses the cornea. The diameter of the ray tracing zone is 4 mm. The number of points in this example is 128. The points are designated in the rectangular coordinates since the acousto-optical deflector operates in X-Y planes.

[0030] FIG. 5 shows an example of a pattern of beam projections on retina (retina spot diagram) for the eye with higher-order aberrations and not compensated defocus. The size of the retinal zone covered by the retina spot diagram is about 60 pm.

[0031] FIG. 6. Similarly to FIG. 4, a pattern of points in the pupil plane is demonstrated containing only the peripheral circle of 37 points. The diameter of the ray tracing zone is the same: 4 mm.

[0032] FIG. 7 is the retina spot diagram painted by the pattern of points of FIG. 6. The eye has insignificant higher-order aberrations and not compensated defocus. The size of the retinal zone covered by the retina spot diagram is about 35 pm.

[0033] FIG. 8 shows the shape of the signal along the x-coordinate (x profile) from the profile sensor 14 (FIG. 1 ). With certain approximation, it is projection on the XOZ plane of a local point spread function, that is one of the descriptors of the visual acuity. Signal values are given in arbitrary units of digitization. The metrics of the x axis is in pixels, where the pixel is the element of 512x512 matrix. FIG. 9 shows the same signal as in FIG. 8, but its / component. Comparison of both projections discovers a small difference in position of the maximum in x and y components, that is within tolerances of eye positioning.

[0034] FIG. 10 represents a projection pattern similar to FIG. 7 but designed in polar p-(p coordinates. It demonstrates coordinate shift of the session “7 seconds after blink” (solid line) in regard to “1 second after blink” (dotted line) caused by saccade movements of the eye.

[0035] FIG. 11 continues comparison of projection patterns of the same 7s vs 1 s sessions with another patient, discovering changes caused by accommodation movements of the crystalline lens of the eye.

[0036] FIG. 12 shows the algorithm of the device operation including translation necessary to compensate for saccade fluctuations (FIG. 10) and scaling to compensate for accommodation fluctuations (FIG. 11 ). The algorithm takes care about reconstruction of the maps giving information about the tear film dynamics revealed by the variations illustrated in FIG. 3.

[0037] FIG. 13 demonstrates the comparison of retina spot diagrams of the peripheral patterns like those of FIG. 10 and FIG. 11 (solid for 7s vs dotted for 1 s) after saccade and accommodation fluctuations are compensated (operations B 02 and B 04 are fulfilled).

[0038] FIG. 14 and FIG. 15 compare the widths of the point spread functions (as represented by the signals from profile sensor 14) 7s and 1 s after blink. Magnified insets show the curve at 7s (FIG. 15) wider than that at 1 s (FIG. 14): W7s>wis. Curves are preliminary equalized in their amplitudes, and the comparison is made at 0.7 level of the maximal value.

[0039] FIG. 16 and FIG. 17 (in a similar manner to FIG. 14 and FIG. 15) compare the amplitudes of the signals from profile sensor 14, x coordinate (7s vs 1 s after blink showing about four times smaller amplitude - 3918 vs 13408 digital units). Simultaneously, the position of the maximum is shifted by 28 pixels.

[0040] FIG. 18 shows an example of one of the series of frames with maps of projection shifts in the process of tear film variations with time. The maps are generally color coded. The larger shifts are coded here with spot brightness: the larger the shift, the brighter the spot. X and Y scaling is in mm.

[0041] FIG. 19 is another example of a frame representing the change of the spread (width) of the light spots on the retina captured several seconds after a blink. As compared with the maps of FIG. 18, spline smoothing is applied. X and Y scaling in FIG. 19 is in pm.

[0042] FIGS. 20A-20E show a series of frames of spread mapping for five consecutive time moments with one second intervals. X and Y scaling is in pm. DETAILED DESCRIPTION OF THE INVENTION

[0043] As used herein, the articles “a” and “an” when used in conjunction with the term “comprising” in the claims and / or the specification, may refer to “one”, but it is also consistent with the meaning of “one or more”, “at least one”, and “one or more than one”. Some embodiments of the invention may consist of or consist essentially of one or more elements, components, method steps, and / or methods of the invention.

[0044] As used herein, the term “or” in the claims refers to “and / or” unless explicitly indicated to refer to alternatives only or the alternatives are mutually exclusive, although the disclosure supports a definition that refers to only alternatives and “and / or”

[0045] As used herein, the terms “comprise” and “comprising” are used in the inclusive, open sense, meaning that additional elements may be included.

[0046] As used herein, the terms “consists of” and “consisting of” are used in the exclusive, closed sense, meaning that additional elements may not be included.

[0047] As used herein, the term “includes” or “including” refers to “including, but not limited to”. The terms “includes, “including” and “including, but not limited to” are used interchangeably

[0048] As used herein, the term “about” to a numeric value, including, for example, whole numbers, fractions, and percentages, whether or not explicitly indicated. The term “about” generally refers to a range of numerical values (e.g., ± 5-10% of the recited value) that one of ordinary skill in the art would consider equivalent to the recited value (e.g., having the same function or result). In some instances, the term “about” may include numerical values that are rounded to the nearest significant figure. In a non-limiting example, a value of about 60 pm encompasses 56 m to 66 m.

[0049] As used herein, the ordinal adjectives “first” “second” and “third”, unless otherwise specified are used to describe a common object, merely indicate that different instances of like objects are being referred to, and are not intended to imply that the objects so described must be in a given sequence, either temporally, spatially, in ranking, or in any other manner.

[0050] In one embodiment of the present invention, there is provided a method for analyzing ocular tear film dynamics based on after-blink measurement sessions of information acquisition on changing optical properties of an eye caused by the tear film dynamics, comprising reconstructing the information from a laser ray tracing with specified time intervals between sessions, each of the sessions of laser ray tracing comprising sequential-in-time laser probing of the eye in a set of points within an aperture of the eye, and detecting laser beam projections on a retina, wherein the eye is oriented along an optical axis of probing. Further to this embodiment, the method comprises reconstructing a two-dimensional distribution of changing optical properties of the eye caused by the tear film dynamics; and displaying the two-dimensional distribution as a map of tear film dynamics.

[0051] In both embodiments, probing of the eye may be performed with an instrumentally compensated ametropia of the eye; wherein a configuration of the set of points is the same in each of the sessions of probing, whereby each of the points of probing represents the same point of the eye aperture in each session. In both embodiments, the laser ray tracing information may be compared between a current session and a reference session that is any previous-in-time session. Particularly, the previous-in-time session is an initial after-blink session.

[0052] In one aspect of both embodiments, the ray tracing information may comprise a width of a registered light intensity profile of laser beam projection on the retina representing a point spread function for each probing point. A representative example is a width measured at a certain level of the light intensity profile.

[0053] In another aspect of both embodiments, the ray tracing information may comprise a total intensity of the registered light intensity profile of laser beam projection on the retina in each probing point, where the total intensity is normalized relative to a maximal value of the total intensity among all probing points of the current session.

[0054] In yet another aspect of both embodiments, the ray tracing information may comprise a difference between positions of the laser beam projections on the retina of the current session and of the reference session.

[0055] In both embodiments and all aspects thereof, the difference between positions of laser beam projections on the retina is calculated after compensation of accommodative and saccadic movements of the eye. In these embodiments and aspects thereof, geometrical centers of the to be compared sets of coordinates are calculated and a translation value is calculated that is the distance between the geometrical centers; mean values of radial distances from the geometrical centers of all points in each of the to be compared sets of coordinates are calculated and a scaling value is calculated that is the ratio of the mean values of radial distances; and an affine transformation of the set of coordinates of each session is made regarding a reference session on the calculated translation and scaling values.

[0056] In another embodiment of the present invention, there is provided a device for analyzing the ocular tear film dynamics, comprising a video camera with a first objective lens configured to conjugate the video camera with a pupil of an eye; an optometric target with a second objective lens configured to enable the conjugation of the optometric target with a retina of the eye; a laser with an acousto-optical scanner and a collimating lens in a ray tracing configuration on a path into the eye; a profile sensor with a third objective lens on the path from the eye; a synchronizer; an acousto-optical deflector; and a processing unit connected through a bus to the video camera, the optometric target, the laser, the acousto-optical deflector and the profile sensor; and a display disposed at an output on the processing unit.

[0057] Further to this embodiment, the device comprises on the path into the eye after the collimating lens, a first fluidic lens and a telescope lens installed in a configuration that enables compensation of the defocus component of eye ametropia for laser beams probing the eye; on the path from the eye after the telescope lens, a second fluidic lens is installed in a configuration that enables compensation of a defocus component of eye ametropia for images of laser projections on the retina; a first beam splitter positioned to split optical paths to the eye and from the eye to the video camera; a second beam splitter positioned to split an optical path to the profile sensor; and a third beam splitter positioned to split an optical path to the optometric target.

[0058] In both embodiments, the processing unit may comprise a memory block configured to accept data of all after-blink sessions from the profile sensor; a translation block connected with its inputs to the profile sensor and to the memory block; a scaling block connected with its inputs to the translation block and the memory block; a coordinate variation block connected with its inputs to the scaling block and to the memory block; a coordinate variation mapping block connected with its input to the coordinate variation block; a projection parameter block connected with its inputs to the profile sensor and to the memory block; a projection parameter mapping block connected with its input to the projection parameter block; and a dynamics mapping block connected with its inputs to the projection parameter mapping block and to the coordinate variation mapping block and connected with its output to the display.

[0059] Provided herein are methods and devices for analyzing ocular tear films of one or both eyes. The structure of the device implementing the proposed method is shown in FIG. 1. The device contains a laser 1 , a two-coordinate scanner 2, a collimating lens 3 (CL), a first fluidic lens 4 (FLi), a first bean splitter 5 (BSi), a telescope lens 6 (TL), and a second beam splitter 7 (BS2), forming and delivering a laser beam pattern to the patient eye 8, a single point of the pattern at a time. The device also contains a first objective lens 9 OL1) and a video camera

[0060] 10 optically conjugated with the entrance pupil of the eye 8. There is also a second fluidic lens

[0061] 11 (FL2), a third beam splitter 12 (BS3), a second objective lens 13 (OL2) positioned on the path of image delivery to a profile sensor 14 (PS) from the laser pattern projected on the retina of the eye 8. An optometric target 15 with a third objective lens 16 (OL3) in front of it is optically connected to the path into the eye 8 through the third beam splitter 12 (BS3). A processing unit 17 with a display 18 at its output is connected to the output of the profile sensor 14. Connection of the processing unit 17 with the laser 1 , the two-coordinate scanner 2, the first fluidic lens 4, the second fluidic lens 11 , the profile sensor 14, and the target 15 are interconnected via a bus 19. The structure of the processing unit 17 is discussed after description of the specificity of signals and their features influenced by the tear film dynamics having dry eye syndrome.

[0062] The laser 1 can operate either in pulse mode or in CW mode. In any of these modes, the laser beam is kept in a certain point of the entrance aperture of the eye for a certain time, usually of the order of a millisecond. Then, in a microsecond time interval, it is switched to another point by the two-coordinate scanner 2. A preferred type of scanner 2 is the acoustooptic one due to its fast operation. The collimating lens 3 CL with its front focus coinciding with the center of scanning of the two-coordinate scanner 2 converts the angular scanning provided by the scanner 2 into the beam repositioning in parallel to the optical axis of the collimating lens 3 CL. Due to fast beam repositioning (about three order shorter than the eye exposing in any of the aperture points), the CW mode of laser operation is acceptable for the design using the acousto-optical scanner. The telescopic system composed of the first fluidic lens FLi (4) and the telescopic lens TL (5) provides correction of the beam tilt in the process of eye probing.

[0063] FIG. 2 illustrates projection of a thin / -th laser beam in the eye. The pupillary system of coordinates is designated as X-Y, and the retinal coordinate system is designated as x-y. The beam crosses the plane of the pupil in point with coordinates (X, Yi). It hits the plane of retina in point (x,, y). The procedure of eye probing is repeated in each session in the same points. The shown example is for a hyperopic eye.

[0064] The beam trajectory in the eye depends, in a certain part, on the state of the corneal surface covered by the tear film. The profile of the tear film changes after each blink. Local changes of its thickness result in changing the beam direction and, therefore, in changing the coordinates ,, y, of the hit point on retina. FIG. 3 illustrates different shifts of the maximal value of the signal 7 s after blink as compared to the shift 1 s after blink: xmax(is) vs xmax(7s). Tear film drying makes its surface rougher resulting in more scatter: the retinal spot becomes larger. The width w7sis larger than wis. Energy loss due to scattering and rise of absorption result in smaller amplitude of the signal: A7S<AIS. These are the features used for analyzing the tear film dynamics and diagnosing the dry eye condition.

[0065] The pattern created by the beam entrance points can be designed with any configuration covering the whole aperture. The most widely used is a concentric grating with uniformly distributed nodes, up to 256 or even more, providing acceptable accuracy for the polynomial description of the wave front surface. A typical pattern of 128 points presented in a rectangular coordinate system is shown in FIG. 4. Rectangular X-Y coordinates are used based on the orthogonal deflection control by the acousto-optical deflector 2. In the shown example, the grating covers the pupil of 4 mm in diameter. The projection of the pattern of FIG. 4 on the retina looks like shown in FIG. 5. Its spreading from the central point depends on the optical power of the eye (degree of the defocus component). In the illustration, the spreading is limited by ±30 pm in both, x and y directions. Added non-uniformity of the distribution is the result of other aberrations including those depending on the tear film. To easier track the shifts of multiple projections on the retina, a simplified pattern is used on the stage of device adjustment (see FIG. 6 for the simplified probing pattern, and FIG. 7 for the projections of this pattern on the retina).

[0066] The x and y profiles of laser projections on retina and their centers of gravity are measured with profile sensor 14 (PS). Hamamatsu profile sensor of the S15366 series is a good (but not limiting) solution for the purposes of this invention, providing the data with the rate 3256 frames per second. Examples of such x and y profiles are shown in FIG. 8 and FIG. 9 correspondingly. The profiles are the local point spread functions (PSF), i.e., the point spread functions of the optics of the eye within the aperture corresponding to the cross-section of the laser beam. Coordinates of the laser projection are measured in pixels as coordinates of the maximal value of the signal: in the given example, it shows 266 pixels (meaning +10 pixels from the middle) in x direction, and 265 pixels (+9 pixels from the middle) in y direction. Signal values in the examples of FIG. 8 and FIG. 9 are given in arbitrary digital units as measured by profile sensor 14.

[0067] Position variations of the laser projections on retina caused by the tear film dynamics take place on the background of saccadic movements of the eye (illustrated by FIG. 10) and accommodation fluctuations (illustrated by FIG. 11 ). Both drawings are made in polar coordinates for the simplified probing pattern containing 37 points of the peripheral circle of the polar 128-node grating. The angular distance between points is 1 / 37 of 2TT, the radial distance is in micrometers. The “7 s after blink” pattern’s outline is in solid line, the “1 s after blink” - in dotted line. The coordinate shift due to saccade movement is downward (FIG. 10). The accommodation (hyperopic eye) is directed to near in the session of “7 s after blink”. Affine transform must be applied: translation to compensate for coordinates shift and scaling - to correct the center-oriented coordinate variation.

[0068] The structure of processing unit 17 is defined by functions required to reconstruct the maps illustrating the degree of position and shape variations of laser beam projections on retina caused by the drying zones of the tear film. The processing unit 17 consists of a memory block 20, a translation block 21 , a scaling block 22, a coordinate variation block 23, a coordinate variation’s mapping block 24, a projection parameter block 25, a projection parameter’s mapping block 26, and a dynamics mapping block 27. The blocks 20, 21 and 25 have their inputs connected to the output of the profile sensor 14. The outputs of the memory block 20 are connected to the inputs of the blocks 21 , 22, 23 and 25. The output of translation block 21 is connected to the input of the scaling block 22, whose output is connected to the input of coordinate variation block 23. The output of block 23 is connected to the input of coordinate variation’s mapping block 24, projection parameter block 25 is connected to the input of projection parameter’s mapping block 26. The outputs of coordinate variation’s mapping block 24 and of projection parameter’s mapping block 26 are connected to the inputs of dynamics mapping block 27, whose output is connected to the input of display 18. An important component of the device is the synchronizer 28, through bus 19 connected to laser 1 , to two-coordinate deflector 2, to first fluidic lens 4 (FLi), to video camera 10, to second fluidic lens 11 (FL2), to optometric target 15, to profile sensor 14, and to processing unit 17 with all its blocks.

[0069] FIG. 12 describes sequence of operations provided by the device implementing the teaching of the proposed method that can be regarded as an algorithm of operations. There are four groups of them. Group A comprises the operations of general type. Group B includes the operations normalizing the data, i.e., minimizing the influence of variations, not related to the dynamics of the tear film. Group C deals with the operations estimating the variations of the projection features. Group D is responsible for the best presentation of the acquired and processed information. Each operation can be a simple one or, a sequence of operations, for example, several mathematical operations needed to get a searched parameter. Hereinafter follows a summary of the operations.

[0070] A 01 . Eye positioning. Watching the screen of the video camera 10, operator assists the patient to orient the head and the eye in the position required for getting sustainable results. The orientation can be towards the center of reflexes from several light source, like light emitting diodes or, other means.

[0071] A 02. Optometric procedures. The optometric target 15 is switched on. Any type of target can be used, like a cross or any miniature display generated figure allowing the patient to concentrate the sight in its direction. The goal of controlling the optical power of the second fluidic lens 11 is to have the target 15 seen most clearly, meaning the target is in focus (defocus component of aberrations is compensated). To get the full conjugation, the first fluidic lens 4 must be set in the same optical power as the second fluidic lens 11 . In this position, not only image blur of laser projections on retina will be minimized, but also, the laser projections on retina will be concentrated in the nearest distance from the center (the minimal RMS), and they will have the smallest possible size.

[0072] A 03. After-blink profile-sensing measurement. The first session after blink must be made in the soonest possible time interval after blink, for example, one second after blink. The x and y profiles are registered, and the positions of their maxima are measured (see FIG. 8 and FIG. 9). A 04. Storing the profile measured data. Storage is provided in memory block 20.

[0073] A 05. Repeating steps A 03 and A 04. Repetition of measurements can be single or multiple. When multiple, sessions follow each other with intervals about one second.

[0074] B 01. Measurement of x-y coordinate shifts in each consecutive session. This step comprises comparison of data of a current session flowing from the profile sensor 14 to the translation block 21 to be compared with the data of any previous session defined to be a reference one, these data flowing from the memory block 20. Comparison is provided pixel- by-pixel, x and / coordinates separately. Coordinate translation is determined as a difference of averaged values of x and y shifts in the current session regarding the reference one.

[0075] B 02. Coordinate translation in each consecutive session. In this step, coordinate shift of each projection point is compensated by the value determined in step B 01. New coordinates of laser projection on retina are ascribed to each probing point of the eye aperture.

[0076] B 03. Measurement of center-oriented coordinate shifts in each session. It is measurement of how spread or shrunk the retina projection pattern is. Rectangular coordinates of each projection point are recalculated into the polar (p,cp) coordinates. In the scaling block 22, based on data of current session coming from the translation block 21 , and on data of a reference session coming from the memory block 20, the scaling coefficient m is calculated. The ratio is measured of radii between current and reference sessions in each point separately, and the average value of this ratio is calculated being the scaling coefficient of the current projection pattern regarding the reference pattern.

[0077] B 04. Coordinate scaling in each consecutive session. It is a simple operation of multiplication by the scaling coefficient m, got in the step B 03. It is provided by the scaling block 22. Applying the procedure of affine transforms of translation and scaling for the peripheral circle of projection points is demonstrated by FIG. 13.

[0078] B 05. Measurement of the position variation of the retinal projection in each consecutive session. To track the dynamics of topographical surface changes induced by the tear film dynamics changing the projection pattern analyzed by coordinate variation block 23, where the coordinate changes in each projection point are measured by comparing coordinates of the reference session delivered from the memory block 20, with coordinates of the current session delivered from the scaling block 22 after they have past the normalization (translation and scaling) in translation block 21 and scaling block 22. This procedure is provided with the point coordinates of the pattern in solid line in FIG. 13 and pattern in dotted line. In the configuration of FIG. 1 , the reference session is the first one after blink. To use any other session for reference, it must be stored in memory block after its normalization in blocks 21 and 22, or after the normalization of the current session in regard to the one chosen for reference. B 06. Reconstruction of the map of refraction variation corresponding to projection position variation in each consecutive session. Convenient form of mapping is a 2D color coded distribution of refraction variation. Refraction variations are represented by the dispersion of coordinate difference calculated, for example, by the technique of sliding window. The shape of the window and the number of analyzed points embraced by the window are outside of the teachings of this patent.

[0079] C 01. Measurement of variation of the projection parameters in each consecutive session. Besides the variation of the projection position on retina measured in steps of group B, the consequences of tear film dynamics are variations of the shape of the projection. Drying tear film results in more scatter of light on the corneal surface leading to a wider projection spot on retina of smaller intensity. Both these parameters are estimated in the projection parameter block 25. Measurement of the width of the spot is illustrated in FIG. 14 and in FIG. 15. As an example, axis x is taken, where the width Ax(1 s) at the level 0.7max is the width parameter for the first session (one second after blink, FIG. 14), and the width Ax(7s) at the level 0.7max is the width parameter for the session made after seven seconds after blink (FIG. 15). Both, x and y, projections can be used for evaluation, as well as their average value.

[0080] FIG. 16 and FIG. 17 illustrate measurement of changes of the amplitude of the x-axis graph from the profile sensor 14. It shows that in the session “7 seconds after blink”, the graph is lower than that in the session “1 second after blink”: amplitude becomes smaller: [AX(7S)<AX(1S)], AX(7S> being 3918 digital units, and AX(is) being as high as 13408 digital units in the analyzed case.

[0081] C 02. Mapping of the projection dynamics. This step is provided by the dynamics mapping block 27 based on information from the coordinate variation’s mapping block 24 and projection parameters mapping block 26. The maps based of three different criteria are at the input of block 27: 1 ) coordinate shifts of laser beam projections on retina - from block 24, 2) variation of the width of the projections - from block 26, 3) variation of the amplitude of the projections - also from block 26 (FIG. 18). The results of mapping in FIG. 18 are presented without “smoothing” the transitions between neighboring points. Usually, the maps are color coded. In their black and white version, the larger shifts of coordinates are coded in this figure with spot brightness: the larger the shift, the brighter the spot.

[0082] An example of the frame representing the changes of the spread (width) of the light spots on the retina are shown in FIG. 19. The data for the frame was acquired several seconds after a blink. The reconstruction was made with spline “smoothing”.

[0083] D 01. Displaying the results of analysis of the tear film dynamics. Depending on the mode, chosen by operator, block 27 dispatches either one of these maps, or all of them, or any combination of them to display 18. Dynamics mapping block 27 analyzes statistical activity of coordinate and shape variations in each session and displays it in time-sequential frames. An example of process dynamics is given in FIGS. 20A-20E representing a series of frames of spread mapping for five consecutive time moments with one second intervals. Each of the maps corresponds to the difference in spreads with the reference frame that itself was acquired in one second after a blink.

[0084] References cited herein:

[0085] 1 . J. Bron. Surv. Ophthalmol. 45(Suppl 2):S221-S226, 2001 .

[0086] 2. Roy, et al. Imaging and Applied Optics, OSA, JW4A.18:1-2, 2018.

[0087] 3. Tan, et al. Infrared Phys. Technol. 52(4):97-108, 2009.

[0088] 4. Licznerski, et al. J. Biomed. Opt. 4(1 ): 176-182, 1999.

[0089] 5. Azartash, et al. Biomed. Opt. Express, 1 :1127-1137, 2010.

[0090] 6. Iskander, et al. IEEE Trans. Biomed. Engng, 52:1939-1949, 2005.

[0091] 7. Gruppetta, et al. Opt. Let., 30:2757-2759, 2005.

[0092] 8. Koh, et al. Invest. Ophthalm. & Vis. Sci, 47:3318-3324, 2006.

[0093] 9. Neay, et al. International Publication WO 2018 / 156805.

Claims

WHAT IS CLAIMED IS:

1. A method for analyzing ocular tear film dynamics based on after-blink measurement sessions of information acquisition on changing optical properties of an eye caused by the tear film dynamics, comprising: reconstructing the information from a laser ray tracing with specified time intervals between sessions, each of said sessions of laser ray tracing comprising sequential-in-time laser probing of the eye in a set of points within an aperture of the eye, and detecting laser beam projections on a retina, wherein the eye is oriented along an optical axis of probing.

2. The method of claim 1 , wherein said probing of the eye is performed with an instrumentally compensated ametropia of the eye; wherein a configuration of the set of points is the same in each of the sessions of probing, whereby each of said points of probing represents the same point of the eye aperture in each session.

3. The method of claims 1 or 2, wherein the laser ray tracing information is compared between a current session and a reference session that is any previous-in-time session.

4. The method of claim 3, wherein the previous-in-time session is an initial afterblink session.

5. The method of any one of claims 1 to 4, wherein the ray tracing information comprises a width of a registered light intensity profile of laser beam projection on the retina representing a point spread function for each probing point.

6. The method of claim 5, wherein said width is measured at a certain level of the light intensity profile.

7. The method of any one of claims 1 to 4, wherein the ray tracing information comprises a total intensity of the registered light intensity profile of laser beam projection on the retina in each probing point, said total intensity normalized relative to a maximal value of the total intensity among all probing points of the current session.

8. The method of any one of claims 1 to 4, wherein the ray tracing information comprises a difference between positions of the laser beam projections on the retina of the current session and of the reference session.

9. The method of any one of claims 1 , 2, 3, 4, or 8, wherein the difference between positions of laser beam projections on the retina is calculated after compensation of accommodative and saccadic movements of the eye.

10. The method of claim 9, wherein: geometrical centers of the to be compared sets of coordinates are calculated and a translation value is calculated that is the distance between the geometrical centers; mean values of radial distances from said geometrical centers of all points in each of the to be compared sets of coordinates are calculated and a scaling value is calculated that is the ratio of said mean values of radial distances; and an affine transformation of the set of coordinates of each session is made regarding a reference session on the calculated translation and scaling values.11 . The method of any one of claims 1 to 10, further comprising: reconstructing a two-dimensional distribution of changing optical properties of the eye caused by the tear film dynamics; and displaying the two-dimensional distribution as a map of tear film dynamics.

12. A device for analyzing the ocular tear film dynamics, comprising: a video camera with a first objective lens configured to conjugate said video camera with a pupil of an eye; an optometric target with a second objective lens configured to enable the conjugation of the optometric target with a retina of the eye; a laser with an acousto-optical scanner and a collimating lens in a ray tracing configuration on a path into the eye; a profile sensor with a third objective lens on the path from the eye; a synchronizer; an acousto-optical deflector; a processing unit connected through a bus to the video camera, the optometric target, the laser, the acousto-optical deflector and the profile sensor; and a display disposed at an output on said processing unit.

13. The device of claim 12, further comprising: on the path into the eye after said collimating lens, a first fluidic lens and a telescope lens installed in a configuration that enables compensation of the defocus component of eye ametropia for laser beams probing the eye; on the path from the eye after the telescope lens, a second fluidic lens is installed in a configuration that enables compensation of a defocus component of eye ametropia for images of laser projections on the retina; a first beam splitter positioned to split optical paths to the eye and from the eye to the video camera; a second beam splitter positioned to split an optical path to the profile sensor; and a third beam splitter positioned to split an optical path to the optometric target.

14. The device of claims 12 or 13, wherein the processing unit comprises: a memory block configured to accept data of all after-blink sessions from the profile sensor; a translation block connected with its inputs to the profile sensor and to the memory block; a scaling block connected with its inputs to the translation block and the memory block; a coordinate variation block connected with its inputs to the scaling block and to the memory block; a coordinate variation mapping block connected with its input to the coordinate variation block; a projection parameter block connected with its inputs to the profile sensor and to the memory block; a projection parameter mapping block connected with its input to the projection parameter block; and a dynamics mapping block connected with its inputs to the projection parameter mapping block and to the coordinate variation mapping block and connected with its output to the display.

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