WO2018202929A2

WO2018202929A2 - Method for determining tear film dynamics and associated computer program products

Info

Publication number: WO2018202929A2
Application number: PCT/ES2018/070336
Authority: WO
Inventors: Mikel ALDABA ARÉVALO; Jaume Pujol Ramo; Alejandro MIRA AGUDELO; John Fredy BARRERA RAMÍREZ
Original assignee: Universitat Politècnica De Catalunya; Universidad De Antioquia
Priority date: 2017-05-05
Filing date: 2018-05-03
Publication date: 2018-11-08
Also published as: WO2018202929A3; ES2688742A1; ES2688742B2

Abstract

The claimed method consists in capturing with a camera for a given period of a time an image of light reflected by the tear film of an eye, in order to produce a series of images; and to process the images, including an analysis of the images by a computer system, wherein the analysis includes identifying the existence of certain structures in the images and linking them to a tear film rupture period, these structures being due to holes in the tear film that cause diffraction, interference and phase changes due to the holes themselves and/or to speckles caused by exposure of the corneal epithelium.

Description

DESCRIPTION

Method for determining the dynamics of tear film and computer program products thereof

Field of the art The present invention generally concerns non-invasive methods used to analyze the ocular tear film. In particular, the invention concerns a method, and computer program products, for determining the dynamics of tear film.

Background of the invention

The tear film is the first surface in contact with the eye. It protects the ocular surface, softens the corneal irregularities and is the first refractive surface of the eye. When its normal function is disturbed, dry eye syndrome appears, a multifactorial disease of the tear film and ocular surface that results in symptoms of discomfort, visual disturbance and instability with potential damage to the ocular surface.

After blinking, the tear film is regenerated in a process that takes a few seconds, then degrades and finally breaks. Despite the discrepancy in how tear film rupture occurs, there is general agreement about the appearance of dry spots or tears in the tear film when flickering is prevented. Dry spots on the tear film cause abrupt differences in surface height and also the smoothness of the surface may be lost if the corneal epithelium is exposed. When illuminated with coherent light, the specular reflection of the cornea can be altered by the presence of structures due to the appearance of dry spots or holes (dry-spots in English) that cause diffraction, interference and phase change due to own hole and speckle (speckle interferometry) due to exposure of the corneal epithelium. Fig. 1 shows an example of this fact. The most common tests in clinical practice for the diagnosis of dry eye are questionnaires, tear film stability or evaluation of tear time, stains and reflex tear flow. However, in recent years a great effort has been made to develop objective and non-invasive methods for dry eye analysis based on new technologies [1], such as corneal topography [2-3], different interferometric techniques [ 4-6], OCT [7], and / or double-step techniques [8].

On the other hand, some patents and / or patent applications are also known in the prior art. US-B2-8256898 discloses a non-invasive method to quantify the thickness of the tear and morphological characteristics thereof where an interference pattern based on speckle is used.

US-B2-8641 194 describes a method for characterizing, in vivo, the dynamics of tear using phase shift interferometry. This interferometer continuously measures the reflected light of the tear film, allowing an accurate analysis of the dynamic surface topography of the tear.

US-A1-2015022658 patent application discloses different techniques for noise reduction, optical measurements and interferometry. A measurement method and system includes illuminating an object to be measured with light at two different wavelengths and an angle of incidence; capture an image of the object; detect a frequency of an interference pattern from the image using Fractional Bi-Spectrum Analysis; and calculate an object thickness based on the Fractional Bi-Spectrum Analysis. The thickness is calculated based on a relationship between the thickness and the frequency of the interference pattern. Fractional Bi-Spectrum Analysis is performed in a linear medium with the two different wavelengths.

References:

[1] McGinnigle, S., Naroo, S. A., & Eperjesi, F. (2012). Evaluation of dry eye. Survey of Ophthalmology, 57 (4), 293-316. http://doi.Org/10.1016/j.survophthal.201 1 .1 1 .003

[2] Kojima, T., Ishida, R., Dogru, M., Goto, E., Takano, Y., Matsumoto, Y., ... Tsubota, K. (2004). A new noninvasive tear stability analysis system for the assessment of dry eyes. Investigative Ophthalmology & Visual Science, 45 (5), 1369-74. http://doi.org/10.1 167 / iovs.03-0712

[3] Németh, J., Erdélyi, B., Csákány, B., Gáspár, P., Soumelidis, A., Kahlesz, F., & Lang, Z. (2002).

High-speed videotopographic measurement of tear film build-up time. Investigative Ophthalmology & Visual Science, 43 (6), 1783-90. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/12036979

[4] Dubra, A., Paterson, C, & Dainty, C. (2004). Study of the tear topography dynamics using a lateral shearing interferometer. Optics Express, 12 (25), 6278-88. http://doi.org/10.1364/OPEX.12.006278

[5] Prydal, J. I., Artal, P., Woon, H., & Campbell, F. W. (1992). Study of human precorneal tear film thickness and structure using laser interferometry. Investigative Ophthalmology & Visual Science, 33 (6), 2006-1 1. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/1582805

[6] Szczesna, D. H., & Iskander, D. R. (2010). Lateral shearing interferometry for analysis of tear film surface kinetics. Optometry and Vision Science: Official Publication of the American Academy of Optometry, 87 (7), 513-7. http://doi.org/10.1097/OPX.0b013e3181 e17279

[7] Ibrahim, O. M. A., Dogru, M., Takano, Y., Satake, Y., Wakamatsu, T. H., Fukagawa, K., ...

Fujishima, H. (2010). Application of visante optical coherence tomography tear meniscus height measurement in the diagnosis of dry eye disease. Ophthalmology, í 7 (10), 1923-9. http://doi.org/10.1016/j.ophtha.2010.01 .057

[8] Benito, A., Pérez, G. M., Mirabet, S., Vilaseca, M., Pujol, J., Marín, J. M., & Artal, P. (201 1).

Objective optical assessment of tear-film quality dynamics in normal and mildly symptomatic dry eyes. Journal of Cataract and Refractive Surgery, 37 (8), 1481-7. http://doi.Org/10.1016/j.jcrs.201 1 .03.036

Exhibition of the invention

The present invention provides in a first aspect a method for determining the dynamics of the tear film, which comprises, as well as the methods known in the state of the art, capturing, by a camera, every certain period of time, for example each medium second, an image of the light reflected in the tear film of an eye (for example a patient's eye), obtaining a series of images.

Unlike the known methods, the proposed method further comprises performing a processing that includes an analysis of some or all of the aforementioned images by a computer system, with one or more processors, operatively connected to said camera, said analysis comprising identify / determine the existence of structures in the images defined by lines that differ from the background of the images, for example white lines, and relate them to a tear film tearing time (i.e. the time interval between the last blink and the appearance of holes ("dry-spots") in the tear film, when flickering is prevented), where said structures are due to said holes in the tear film, which causes diffraction, interference and change of phase due to the hole itself and speckle due to the exposure of the corneal epithelium.

Preferably, prior to said capture, the eye is irradiated with a beam of light, non-invasively by a light source, for example a laser light source consistent with a determined wavelength, preferably 780 nanometers. Alternatively, the proposed method, instead of irradiating the patient's eye, although this irradiation is non-invasive for the patient, can be initiated with the storage, in a database (or a memory), of the images obtained by said camera . Subsequently, the method would perform the processing of some or all images by the aforementioned computer system as described in the previous paragraph.

In a first embodiment, said analysis is carried out by means of the implementation by said computer system of a first computing algorithm that extracts different identifying parameters of the texture of the tear film in said images, depending on the number of structures identified. Where said texture identifying parameters include entropy and contrast, among others. In a second embodiment, said analysis is performed by the implementation by said computer system of a second computing algorithm that quantifies the structures that appear in the images. Preferably, said quantification comprises binarizing the images, detecting the structures in the images and verifying that the structures detected do not exceed a first threshold value (for example between a range of 7-8 arc minutes, preferably 7.5 arc minutes). According to this second embodiment, if the result of said check indicates that the number of structures detected is greater than a second threshold value (for example greater than 10), the method determines that the tear film has been broken. In a third embodiment, said analysis is carried out by means of the implementation by said computing system of a third computing algorithm that performs a Fourier transform of the captured images and determines the presence of the structures in the images by an increase of The high frequencies.

In a fourth exemplary embodiment, said analysis is carried out by means of the implementation by said computing system of a fourth computing algorithm that performs a cross correlation between a reference image corresponding to the moment after the blink, without the presence of structures, and An image of the captured images that you want to analyze. The presence of structures is determined in this case by the decrease in the cross correlation value obtained. The aforementioned camera comprises a lens, which may be focused or out of focus during image capture. Preferably, the degree of blurring is 2 diopters.

Other embodiments of the invention disclosed herein also include computer program products for performing the steps and operations of the method proposed in the first aspect of the invention. More particularly, a computer program product is an embodiment that has a computer-readable medium that includes computer program instructions encoded therein that when executed in at least one processor of a computer system cause the processor to perform the operations indicated in this document as embodiments of the invention. Brief description of the drawings

The foregoing and other features and advantages will be more fully understood from the following detailed description of some embodiments, which are merely illustrative and not limiting, with reference to the attached drawings, in which: Figs. 1A and 1 B schematically show the corneal reflection of coherent light in A) an eye with a smooth tear film after blinking, B) an eye with dry spots when flickering is prevented.

Fig. 2 shows a schematic view of a system used to implement the proposed method according to an embodiment of the present invention.

Fig. 3 is a flow chart illustrating an exemplary embodiment of the proposed method.

Figs. 4A and 4B show an example of a smooth tear film without holes (dry spots), and consequently without structures due to diffraction, interference, phase changes and / or speckie (Fig. 4A) and an example of a tear film with dry spots, which cause degradation (Fig. 4B) due to the previously mentioned phenomena.

Figs. 5A and 5B show some examples of the images and structures obtained by means of the example of the identification and quantification of structures.

DETAILED DESCRIPTION OF EXAMPLES OF EMBODIMENT The present invention provides a non-invasive method for determining / evaluating the tear film dynamics, by measuring the rupture time based on structures in the corneal reflex caused by dry spots (or holes). ).

Fig. 2 shows an embodiment of the system used to implement the proposed method. According to this embodiment, the system comprises a light source 10, preferably a laser light source consistent with a wavelength of 780 nanometers, a camera 1 1, for example a CCD camera, a lens 12, a beam splitter 13 and a computer system 20 that includes one or more processors and at least one memory and which is operatively connected to said camera 11. Likewise, the system may also comprise a database (or a memory), not illustrated, to store the images obtained by said camera 1 1.

In an exemplary embodiment, the collimated beam of light irradiated by the light source 10 is reflected in the beam splitter 13 and reaches the eye 1, preferably the eye of a human being. The light is reflected on the first surface of the eye, the tear film, and passes through the beam splitter 13. Finally, the image of the reflected light is recorded by the lens 12 that forms the image in the camera 11.

With reference to Fig. 3, there is shown an example of embodiment of the proposed method. The method comprises, step 301, irradiating, by means of said light source 10, a beam of light on the eye 1 and capture, step 302, by means of said camera 1 1, for example every half second, an image of the eye 1 after reflection of the beam in the tear film of the eye 1, obtaining a series of images. Next, step 303, said computer system 20 performs a processing that includes the analysis of the images obtained by identifying / determining the existence of structures in the images (defined by lines that differ from the background of the images) and relating them to a tear film break time. Mainly, the structures are due to diffraction, interference and phase change due to holes in the tear film and speckle due to exposure of the corneal epithelium. When the tear film is smooth and without holes (dry spots), the recorded image has no structures (see Fig. 4A). On the other hand, dry spots degrade the image (Fig. 4B) due to diffraction, interference, phase change and / or speckle.

The capture of the images by the aforementioned camera 11 can be carried out with the objective of the same being focused or out of focus, preferably with a blur of 2 diopters. In an alternative embodiment, instead of performing step 301, the method comprises storing the images captured by camera 11 in said database (or memory) and then performing step 303 as described above. That is, in this case the proposed method would consist of an image processing method to determine the dynamics of the tear film. According to the present invention, the appearance of structures can be identified / detected according to different analysis methodologies or algorithms, for example by means of a Fourier Transform, cross correlation, texture analysis, identification and quantification of structures, etc.

In a first embodiment, said analysis is performed (by a computing algorithm, or second algorithm as indicated in the claims) by quantifying the said structures that appear in the images. For this purpose, the images are binarized and the structures in the images are detected. Next, the identified structures are classified depending on their size (this step is optional, that is, it is not necessary to perform this size classification) and it is verified that the identified structures do not exceed a first threshold value, ranging in a range of 7 - 8 arc minutes, preferably 7.5 arc minutes. When the result of said verification indicates that the number of structures identified is greater than a second threshold value (for example equal to 10 structures), the algorithm determines that the tear film has been broken. In Fig. 5A, processed images (binarized and that only take into account the small structures) are shown. The first image after a blink is shown in the upper left and the following images are ordered from left to right and from top to bottom. The graph of Fig. 5B shows the number of structures identified for each image. As can be seen, and considering that the threshold for detecting the rupture is 10 structures, the rupture in this case is determined between images 3 and 4, which correspond to the second 1.0 and 1.5 respectively.

In a second embodiment, said analysis is performed (by a computing algorithm, or first algorithm) by extracting different identifying parameters of the texture of the tear film in said images based on the number of structures identified. For example, different texture identification parameters may include entropy, contrast, among others.

In other examples of embodiment, as indicated above, the analysis is performed by performing a Fourier Transform of the images or by cross-correlation.

The proposed invention can be implemented in hardware, software, firmware or any combination thereof. If implemented in software, the functions can be stored in or encoded as one or more instructions or code in a computer-readable medium. The computer readable medium includes computer storage media. The storage medium can be any available media that can be accessed by a computer. By way of example, and not limitation, such a computer-readable medium may comprise RAM, ROM, EEPROM, CD-ROM or other optical disk storage, magnetic disk storage or other magnetic storage devices, or any other means that may used to carry or store desired program code in the form of instructions or data structures and that can be accessed by a computer. Disk (disk) and disk (disc) include compact discs (CDs), laser discs, optical discs, digital versatile discs (DVDs), flexible discs and Blu-ray discs where discs (disks) normally reproduce data magnetically, while discs (discs) reproduce data optically with lasers. Combinations of the above should also be included within the scope of computer readable media. Any processor and storage medium can reside in an ASIC. The ASIC can reside in a user terminal. Alternatively, the processor and the storage medium may reside as discrete components in a user terminal. As used herein, computer program products comprising computer-readable media include all forms of computer-readable media except, to the extent that such media is considered to be non-established transient propagation signals. The scope of the present invention is defined in the appended claims.

Claims

1. Method to determine the dynamics of the tear film, the method comprises capturing, for a camera, every certain period of time, an image of a light reflected in the tear film of an eye, obtaining a series of images, the method being characterized in that it also comprises performing a processing that includes an analysis of one or more of said images captured by a computer system, said analysis comprising identifying the existence of structures in the images and relating the identified structures to a film break time. tear, said structures being due to holes in the tear film that cause diffraction, interference and phase change due to the hole itself and / or speckle due to exposure of the corneal epithelium.

2. A method according to claim 1, wherein said series of captured images are stored in a database or in a memory.

3. Method according to claim 1, wherein said analysis is carried out by means of the implementation by said computer system of a first computing algorithm that extracts different identifying parameters of the texture of the tear film in the images according to the number of structures identified , wherein said different parameters include at least entropy and contrast.

4. Method according to claim 1, wherein said analysis is performed by the implementation by said computer system of a second computing algorithm that quantifies said identified structures.

5. Method according to claim 4, wherein said quantification comprises:

- binarize the images;

- detect the structures in the images; Y

- verify that the structures detected do not exceed a first threshold value, where if a result of said verification indicates that the number of structures detected is greater than a second threshold value, the method determines that the tear film has been broken.

6. Method according to claim 5, wherein said first threshold value is between a range of 7-8 arc minutes.

7. Method according to claim 5, wherein the first threshold value is 7.5 arc minutes.

8. Method according to claim 1, wherein said analysis is performed by means of the implementation by said computer system of a third computing algorithm that identifies the structures by means of a Fourier Transform analysis of the captured images.

9. Method according to claim 1, wherein said analysis is carried out by means of the implementation by said computing system of a fourth computing algorithm that identifies the structures by means of a cross-correlation analysis between a reference image corresponding to a moment after a blink, without the presence of structures, and at least one image of the captured images.

10. A method according to claim 1, wherein said camera comprises a lens, said capture being made from the series of images with said lens being focused.

1 Method according to claim 1, wherein said camera comprises a lens, said capture of the series of images being performed, said lens being out of focus with a predetermined degree of blur.

12. Method according to claim 10, wherein said degree of blurring is 2 diopters.

13. Method according to claim 1, wherein prior to said capture the eye is irradiated, by a light source, with a light beam, wherein the light source comprises a laser light source consistent with a determined wavelength .

14. Method according to claim 13, wherein the wavelength is 780 nanometers.

15. Computer program product that includes code instructions that when executed in a processor of a computer system implement said processing of claim 1.

16. Computer program product of claim 12, wherein the code instructions further implement the steps of the method of claims 3, 4, 8 or 9.