A method for evaluating the subject's focusing ability, degree of lens hardening, or progression of presbyopia.

Abstract

To provide a method for evaluating focus adjustment force of an object, a degree of curing of a crystal lens, or a degree of progress of presbyopia.SOLUTION: There is provided a method for evaluating focus adjustment force of an object, a degree of curing of a crystal lens, or a degree of progress of presbyopia with a thickness change rate of a crystal lens indicated by the undermentioned formula 1 in the object as an index. Formula 1; a thickness change rate of a crystal lens={(thickness of the crystal lens (mm) measured by applying a negative accommodation load (D) to objective refractivity (D) of the object)-(thickness of the crystal lens (mm) measured by applying a positive accommodation load (D) to objective refractivity (D) of the object)} / (thickness of the crystal lens (mm) measured by applying a positive accommodation load (D) to objective refractivity (D) of the object)×100(%).SELECTED DRAWING: None

Description

Technical Field

[0001] The present invention relates to a method for evaluating the focusing power of an object, the degree of lens sclerosis, or the degree of progression of presbyopia. The present invention also relates to a method for screening candidate substances that improve focusing power, reduce or maintain the degree of lens sclerosis, or suppress the progression of presbyopia.

Background Art

[0002] Presbyopia (so-called presbyopia) is considered to be the attenuation of focusing power associated with aging. As mechanisms for the occurrence of presbyopia, sclerosis of the lens and atrophy of the ciliary muscle are known (for example, Non-Patent Document 1).

Prior Art Documents

Non-Patent Documents

[0003]

Non-Patent Document 1

Summary of the Invention

Problems to be Solved by the Invention

[0004] Presbyopia is considered to be a stage just before nuclear cataract, and it is expected that measures against presbyopia will delay the onset of cataract and reduce the risk of blindness. As one method for dealing with presbyopia, a method of identifying a substance that improves presbyopia or slows down the progression of presbyopia and administering it is conceivable. However, there has been no known non-invasive method for evaluating the focusing power of an object (especially a human), the degree of lens sclerosis, or the degree of progression of presbyopia.

[0005] Therefore, an object of the present invention is to provide a method for evaluating the focusing power of an object, the degree of lens sclerosis, or the degree of progression of presbyopia. Another object of the present invention is to provide a method for screening candidate substances that improve focusing power, reduce or maintain the degree of lens sclerosis, or suppress the progression of presbyopia. [Means for solving the problem]

[0006] The inventors have found a correlation between the rate of change in lens thickness of the subject, as detailed below, and the subject's age. It is known that the lens hardens with age, reducing its ability to adjust thickness. Therefore, it is considered possible to evaluate focusing ability, the degree of lens hardening, and the progression of presbyopia using the rate of change in lens thickness as an indicator. Furthermore, it is considered possible to identify substances that improve focusing ability, substances that reduce or maintain the degree of lens hardening, and substances that suppress the progression of presbyopia using the rate of change in lens thickness as an indicator.

[0007] This invention relates, for example, to the following inventions. [1] A method for evaluating the focusing ability, degree of hardening of the lens, or degree of presbyopia progression of a subject, using the rate of change in lens thickness represented by the following formula 1 as an indicator. Lens thickness change rate = {(Lens thickness measured by applying a negative accommodation load (D) to the objective refractive error (D) of the subject (mm)) - (Lens thickness measured by applying a positive accommodation load (D) to the objective refractive error (D) of the subject (mm))} / (Lens thickness measured by applying a positive accommodation load (D) to the objective refractive error (D) of the subject (mm)) × 100 (%) ... Equation 1 [2] The method according to [1], wherein the negative accommodation load (D) is between -1D and -15D. [3] The method according to [1] or [2], wherein the positive accommodation load (D) is between +5D and +15D. [4] A method according to any one of [1] to [3], further comprising comparing the rate of change in lens thickness with a reference value. [5] A screening method for candidate substances that improve focusing ability, reduce or maintain the degree of hardening of the lens, or suppress the progression of presbyopia, This includes comparing the rate of change in lens thickness in subjects administered the test substance with the rate of change in lens thickness in subjects not administered the test substance, and selecting the test substance that shows a larger rate of change in lens thickness in subjects administered the test substance as the candidate substance. A method wherein the rate of change in lens thickness is a value calculated by the following formula 1. Lens thickness change rate = {(Lens thickness measured by applying a negative accommodation load (D) to the objective refractive error (D) of the subject (mm)) - (Lens thickness measured by applying a positive accommodation load (D) to the objective refractive error (D) of the subject (mm))} / (Lens thickness measured by applying a positive accommodation load (D) to the objective refractive error (D) of the subject (mm)) × 100 (%) ... Equation 1 [6] The method according to [5], wherein the negative accommodation load (D) is -1D to -15D. [7] The method according to [5] or [6], wherein the positive accommodation load (D) is between +5D and +15D. [Effects of the Invention]

[0008] The present invention provides a method for evaluating the focusing ability, degree of hardening of the lens, or degree of presbyopia progression of a subject. The present invention also provides a method for screening candidate substances that improve focusing ability, reduce or maintain the degree of hardening of the lens, or suppress the progression of presbyopia. [Brief explanation of the drawing]

[0009] [Figure 1] This graph shows the correlation between the rate of change in lens thickness of a subject, measured under accommodation loads of objective refractive error (D) -6D and objective refractive error (D) +10D, and the subject's age. [Figure 2]This graph shows the correlation between the rate of change in lens thickness of a subject, measured under accommodation loads of objective refractive error (D) -3D and objective refractive error (D) +10D, and the subject's age. [Figure 3] This graph shows the correlation between the rate of change in lens thickness of a subject, measured under accommodation loads of objective refractive error (D) -10D and objective refractive error (D) +10D, and the subject's age. [Modes for carrying out the invention]

[0010] The embodiments for carrying out the present invention will be described in detail below. However, the present invention is not limited to the following embodiments.

[0011] [Method for evaluating the subject's focusing ability, degree of lens hardening, or progression of presbyopia] The method for evaluating the focusing ability, degree of hardening of the lens, or degree of presbyopia progression of a subject according to this embodiment includes evaluating the focusing ability, degree of hardening of the lens, or degree of presbyopia progression of the subject using the rate of change in lens thickness as an indicator.

[0012] In this specification, "rate of change in lens thickness" is the value defined by the following formula 1. Lens thickness change rate = {(Lens thickness measured by applying a negative accommodation load (D) to the objective refractive error (D) of the subject (mm)) - (Lens thickness measured by applying a positive accommodation load (D) to the objective refractive error (D) of the subject (mm))} / (Lens thickness measured by applying a positive accommodation load (D) to the objective refractive error (D) of the subject (mm)) × 100 (%) ... Equation 1

[0013] In this specification, a point at a distance corresponding to "applying a negative accommodation load to the objective heterophoric refractive power (D)" may be referred to as a "near point" for convenience. Similarly, in this specification, a point at a distance corresponding to "applying a positive accommodation load to the objective heterophoric refractive power (D)" may be referred to as a "far point" for convenience. The near point is closer to the subject than the far point. When rephrasing Equation 1 using these terms, it becomes as follows. Lens thickness change rate = {(lens thickness (mm) when focusing on the near point) - (lens thickness (mm) when focusing on the far point)} / (lens thickness (mm) when focusing on the far point) × 100 (%)... Equation 1'

[0014] The objective heterophoric refractive power (D) of the subject can be measured, for example, using a refractometer. The unit of heterophoric refractive power is "D" (diopter). The objective heterophoric refractive power (D) of the subject is usually within the range of approximately -11D to 1D.

[0015] The nearest point is a point at a distance corresponding to a negative accommodation load applied to the object's objective refractive error (D), and the thickness of the lens increases as the object attempts to focus on the nearest point. The nearest point may be, for example, a point at a distance corresponding to a refractive error (D) obtained by subtracting 1 to 15 D from the object's objective refractive error (D) (i.e., a negative accommodation load (D) of -1 D to -15 D). The value subtracted from the object's objective refractive error (D) (1 to 15 D above) may be, for example, 3 to 10 D (i.e., a negative accommodation load (D) of -3 D to -10 D). Furthermore, it is preferable that the value subtracted from the object's objective refractive error (D) exceeds the object's accommodative power (D). This strengthens the correlation between the rate of change in lens thickness and age. The accommodative power (D) of a subject is expressed as 1 / n-1 / f, where f(m) is the distance to the far point (the point in the external world that is imaged in the fovea in an unaccommodated state) and n(m) is the distance to the near point (the point that is imaged in the fovea in an extremely accommodative state). It is known that accommodative power decreases with age; for example, it is approximately 12-14D at age 10, 8-10D at age 20, 6-7D at age 30, 4-5D at age 40, 2-4D at age 50, 0-2D at age 60, and 0-1D at age 70. Using these values ​​as a reference, a value to subtract from the subject's objective refractive error (D) can be set according to the subject's age (or the average age of the subject group). For example, if the age of the subject (or the average age of the subject group) is 38 to 42 years, it is preferable to set the value to be subtracted from the subject's objective refractive error (D) to a value greater than approximately 4 to 5D, i.e., within the range of 5 to 7D (i.e., a negative accommodation load (D) of -5D to -7D), and more preferably to 6D (i.e., a negative accommodation load (D) of -6D).

[0016] The far point is a point at a distance corresponding to applying a positive accommodation load to the objective heterophoric refractive power (D). When the subject tries to focus on the far point, the thickness of the crystalline lens does not increase. The far point may be, for example, a point at a distance corresponding to a refractive power (D) obtained by adding 5 to 15 D to the objective heterophoric refractive power (D) of the subject (that is, the positive accommodation load (D) is +5 D to +15 D). The value added to the objective heterophoric refractive power (D) of the subject (5 to 15 D above) may be, for example, 8 to 12 D (that is, the positive accommodation load (D) is +8 D to +12 D), or may be 10 D (that is, the positive accommodation load (D) is +10 D). Also, the value added to the objective heterophoric refractive power (D) of the subject is preferably a value exceeding the accommodation power (D) of the subject. Thereby, when focusing on the far point, a foggy state can be approximately created, and the correlation between the rate of change of the crystalline lens thickness and age becomes stronger. From this viewpoint, the far point may be the far point (the point in the external world that forms an image on the fovea centralis of the retina in the unaccommodated state).

[0017] The thickness (mm) of the subject's crystalline lens can be measured, for example, using an optical coherence tomography (OCT) (for example, trade name: CASIA2, manufactured by Tomei Corporation).

[0018] The method for evaluating the focusing power, the degree of sclerosis of the crystalline lens, or the degree of progression of presbyopia of the subject according to the present embodiment may further include comparing the rate of change of the subject's crystalline lens thickness with a reference value. The reference value may be appropriately set according to the purpose of implementing the method for evaluating the focusing power, the degree of sclerosis of the crystalline lens, or the degree of progression of presbyopia of the subject according to the present embodiment. For example, when the purpose is a relative evaluation in the same age group of the focusing power, the degree of sclerosis of the crystalline lens, or the degree of progression of presbyopia of the subject, the reference value may be the average value, median value, etc. of the rate of change of the crystalline lens thickness measured in a large number of subjects in the same age group as the subject. Also, for example, when the purpose is to search for a candidate substance that improves the focusing power, reduces or maintains the sclerosis of the crystalline lens, or suppresses the progression of presbyopia, the rate of change of the crystalline lens thickness in the subject before administration of the test substance may be used as the reference value, and the rate of change of the crystalline lens thickness in the subject after administration of the test substance may be compared with this reference value.

[0019] The subjects may be mammals such as humans, monkeys, chimpanzees, mice, rats, and rabbits. Humans are preferred as subjects.

[0020] The present invention can also be considered as a data collection method for evaluating the focusing ability, degree of hardening of the lens, or degree of presbyopia progression of an object, which includes calculating the rate of change in lens thickness represented by the following formula 1 in the object. Lens thickness change rate = {(Lens thickness measured by applying a negative accommodation load (D) to the objective refractive error (D) of the subject (mm)) - (Lens thickness measured by applying a positive accommodation load (D) to the objective refractive error (D) of the subject (mm))} / (Lens thickness measured by applying a positive accommodation load (D) to the objective refractive error (D) of the subject (mm)) × 100 (%) ... Equation 1 The above-described embodiments can be applied without any particular limitations as specific embodiments of the data collection method.

[0021] [Screening method for candidate substances that improve focusing ability, reduce or maintain the degree of hardening of the lens, or suppress the progression of presbyopia] The screening method for candidate substances that improve focusing ability, reduce or maintain the degree of hardening of the lens, or suppress the progression of presbyopia according to this embodiment includes comparing the rate of change in lens thickness in subjects administered with the test substance with the rate of change in lens thickness in subjects not administered with the test substance, and selecting the test substance for which the rate of change in lens thickness in subjects administered with the test substance is greater as a candidate substance.

[0022] Since the screening method according to this embodiment uses the rate of change in lens thickness described above as an indicator, it is possible to select candidate substances that improve focusing ability, reduce or maintain the degree of hardening of the lens, or suppress the progression of presbyopia.

[0023] In this specification, "improving focusing ability" includes slowing down the decline in focusing ability associated with aging (suppressing attenuation), maintaining the focusing ability of the subject, and improving the focusing ability of the subject. Similarly, in this specification, "reducing or maintaining the degree of hardening of the lens" includes slowing down the progression of hardening of the lens associated with aging, maintaining the degree of hardening of the lens of the subject, and reducing the degree of hardening of the lens of the subject. Furthermore, similarly, in this specification, "suppressing the progression of presbyopia" includes slowing down the progression of presbyopia associated with aging, stopping the progression of presbyopia of the subject, and improving presbyopia of the subject.

[0024] There are no particular restrictions on the candidate substances; for example, they may be single substances such as nucleic acids (DNA, RNA, etc.), peptides, low molecular weight compounds, or high molecular weight compounds, or they may be substances (compositions) containing multiple components such as plant extracts. [Examples]

[0025] The present invention will be described more specifically below based on examples. However, the present invention is not limited to the following examples.

[0026] The rate of change in lens thickness was measured in 23 subjects (average age: 38.9 years, age range: 28 to 54 years). All subjects were asked to remove their glasses or contact lenses during the measurement, and the measurements were taken with the naked eye.

[0027] (Measurement of objective refractive error (D)) The objective refractive error (D) of the subjects was measured using a refractometer (product name: Corneal Topography RT-7000, manufactured by Tomei Corporation).

[0028] (Measurement of lens thickness) The lens thickness of the subjects was measured using an optical coherence tomography (OCT) device (product name: CASIA2, manufactured by Tomei Corporation).

[0029] (Calculation of lens thickness change rate) The distant point was defined as the point corresponding to the distance corresponding to the refractive error (D) obtained by adding 10D to each subject's objective refractive error (D) (positive accommodation load of +10D). The nearby point was defined as the point corresponding to the distance corresponding to the refractive error (D) obtained by subtracting 3D, 6D, or 10D from each subject's objective refractive error (D) (negative accommodation load of -3D, -6D, or -10D). Subjects were asked to focus on the distant point and each nearby point, and the thickness of the lens was measured at that time. From the measured lens thickness, the rate of change in lens thickness was calculated according to the following formula 1'. Lens thickness change rate = {(Lens thickness when focused on a nearby point (mm)) - (Lens thickness when focused on a distant point (mm))} / (Lens thickness when focused on a distant point (mm)) × 100 (%) ... Equation 1'

[0030] Figure 1 is a graph showing the correlation between the measured rate of change in lens thickness of the subjects, measured under accommodation loads of objective refractive error (D) -6D and objective refractive error (D) +10D, and the subjects' age. As shown in Figure 1 and Table 1, a high correlation was found between the rate of change in lens thickness and age in both the right and left eyes (correlation coefficients of -0.81 and -0.72), indicating a correlation between the two.

[0031] Figure 2 is a graph showing the correlation between the measured rate of change in lens thickness of the subjects, measured under accommodation loads of objective refractive error (D) -3D and objective refractive error (D) +10D, and the subjects' age. As shown in Figure 2 and Table 1, a correlation (correlation coefficients of -0.65 and -0.64) was observed between the rate of change in lens thickness and age in both the right and left eyes, indicating a correlation.

[0032] Figure 3 is a graph showing the correlation between the measured rate of change in lens thickness of the subjects, measured under accommodation loads of objective refractive error (D) -10D and objective refractive error (D) +10D, and the subjects' age. As shown in Figure 3 and Table 1, a correlation (correlation coefficients of -0.69 and -0.59) was observed between the rate of change in lens thickness and age in both the right and left eyes, indicating a correlation.

[0033] Table 1 shows the numerical data of the calculated rate of change in lens thickness for each subject. [Table 1]

Claims

1. A method for determining the rate of change in lens thickness in a subject, expressed by the following formula 1, as an index for evaluating the focusing ability, degree of hardening of the lens, or degree of progression of presbyopia in the subject. Lens thickness change rate = {(Lens thickness (mm) measured by applying a negative accommodation load (D) to the objective refractive error (D) of the subject) - (Lens thickness (mm) measured by applying a positive accommodation load (D) to the objective refractive error (D) of the subject)} / (Lens thickness (mm) measured by applying a positive accommodation load (D) to the objective refractive error (D) of the subject) × 100 (%) ... Equation 1

2. A data collection method for evaluating the focusing ability, degree of hardening of the lens, or degree of presbyopia progression of a subject, comprising calculating the rate of change of lens thickness represented by the following formula 1 for the subject. Lens thickness change rate = {(Lens thickness (mm) measured by applying a negative accommodation load (D) to the objective refractive error (D) of the subject) - (Lens thickness (mm) measured by applying a positive accommodation load (D) to the objective refractive error (D) of the subject)} / (Lens thickness (mm) measured by applying a positive accommodation load (D) to the objective refractive error (D) of the subject) × 100 (%) ... Equation 1

3. The method according to claim 1 or 2, wherein the negative accommodation load (D) is -1D to -15D.

4. The method according to claim 1 or 2, wherein the positive accommodation load (D) is between +5D and +15D.

5. The method according to claim 3, wherein the positive accommodation load (D) is between +5D and +15D.

6. A screening method for candidate substances that improve focusing ability, reduce or maintain the degree of hardening of the lens, or suppress the progression of presbyopia, This includes comparing the rate of change in lens thickness in subjects administered the test substance with the rate of change in lens thickness in subjects not administered the test substance, and selecting the test substance that shows a larger rate of change in lens thickness in subjects administered the test substance as the candidate substance. A method wherein the rate of change in lens thickness is a value calculated by the following formula 1. Lens thickness change rate = {(Lens thickness (mm) measured by applying a negative accommodation load (D) to the objective refractive error (D) of the subject) - (Lens thickness (mm) measured by applying a positive accommodation load (D) to the objective refractive error (D) of the subject)} / (Lens thickness (mm) measured by applying a positive accommodation load (D) to the objective refractive error (D) of the subject) × 100 (%) ... Equation 1

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