Method for detecting the effect of longitudinal chromatic defocus signals on the development of the refraction of the eye

Abstract

The application provides a detection method for the effect of longitudinal chromatic aberration defocus signals on eye refraction development, which comprises the following steps: obtaining a spectral sensitivity function of human eye cone cells; obtaining a first target defocus signal based on the spectral sensitivity function; performing an influence experiment of a display image longitudinal chromatic aberration defocus signal on human eyes based on the spectral sensitivity function, and obtaining a second target defocus signal; performing an animal level in-vivo detection experiment based on the spectral sensitivity function, and obtaining a third target defocus signal; and performing a molecular level analysis experiment of the effect of the image longitudinal chromatic aberration defocus signal on eye refraction development based on the in-vivo detection experiment. The method provided in the embodiments of the application can analyze the effect of DI-LCA defocus signals on refraction development through cone cells from three levels of tissues, animals and molecules, and preferably target defocus signals, thereby providing support for the research and development of display driving programs and devices for reducing the risk of myopia.

Description

Technical Field

[0001] This application relates to the field of ophthalmic technology, and in particular to a method for detecting the effect of longitudinal chromatic aberration defocus signal on ocular refractive development. Background Technology

[0002] Myopia is becoming increasingly prevalent among adolescents, with the prevalence of childhood myopia rising year by year. Indoor close-range visual activity can easily lead to rapid refractive development, causing myopia, and the prevalence increases with the amount of time children spend using their eyes indoors in close-range environments. Conversely, open outdoor activities can reduce axial elongation and the degree of myopia progression, thus reducing the prevalence and progression of myopia. However, adolescents have limited outdoor activity time, making it of practical significance to reduce the risk of myopia caused by rapid refractive development when children use their eyes indoors in close-range environments.

[0003] Photons are fundamental particles that mediate electromagnetic interactions; they are gauge bosons and are considered the mediators of electromagnetic interactions in quantum mechanics. The basic properties of a single photon include color (frequency), position, direction of propagation, spin (polarization), and wave phase. The human eye can perceive the first three properties. After passing through the eye's refractive system, photons reach cone cells, forming the initial input signal for vision. When many photons are present, visual information can be carried by photon intensity (i.e., brightness), and perception is performed by cone cells. The form and color signals generated on the retina by the visual environment are important factors regulating emmetropization. The form signals that can be perceived by the eye mainly include accommodative stimuli (visual distance), spatial frequency, contrast, and focal length variation curves. Research has found that different form stimuli (accommodative stimuli, spatial frequency, contrast) and color stimuli (red, blue) in the visual environment can regulate refractive development. Among these, the color signal mainly refers to longitudinal chromatic aberration (LCA). LCA (Long Focal Length) refers to the phenomenon where the focal length of longer wavelength light (red light) is longer than that of shorter wavelength light (blue light). When the focal point of a broadband light source (white light) is on the retina, the focal point of shorter wavelength light is in front of the retina, and the focal point of longer wavelength light is behind the retina. The human eye's LCA in the visible light range is 2-3D. The human visual system can effectively regulate emmetropization using this 2-3D LCA. The specific mechanism is as follows: When shorter wavelength light forms a stronger focusing signal on the retina than longer wavelength light, it indicates that the focal point of the eye's refractive system is behind the retina (hyperopic LCA defocus state), generating a regulatory signal that shortens the axial length, thereby promoting axial elongation. Conversely, when longer wavelength light forms a stronger focusing signal on the retina than shorter wavelength light, it indicates that the focal point of the eye's refractive system is in front of the retina (myopic LCA defocus state), generating a regulatory signal that lengthens the axial length, thereby inhibiting axial elongation. This creates a bidirectional regulatory effect on eye refractive development, ensuring emmetropization. Mammals can detect focal acicular defocus (LCA) and initiate a cascade of signals regulating local refractive development in the retina using cone cells sensitive to different wavelengths of light. For example, in dichromatic animals, one group of cone cells is sensitive to short-wavelength light (S cones), while the other group is sensitive to long-wavelength light (L cones). By comparing the intensity of the defocus signal detected by S cone cells with that detected by L cone cells, it is possible to determine whether the LCA defocus is hyperopic or myopic, and to regulate the refractive development of the eyeball through a cascade of signals in the refractive periphery (RPE), choroid, and sclera. Experiments have shown that narrow-bandwidth monochromatic illumination can cause an imbalance in the defocus signals of myopic and hyperopic LCAs, making the refractive development of the eyeball unstable.

[0004] Humans are trichromatic visual animals, possessing additional mid-wavelength sensitive cone cells (M cones) on top of S and L cone cells. However, the human eye's response to accommodative stimuli often exhibits slight errors. When viewing distant objects, accommodation often leads (myopic defocus); when viewing near objects, accommodation lags (hyperopic defocus). Mid-to-high spatial frequency images have been shown to suppress form deprivation myopia. The difference in ERG signals between hyperopic and myopic defocus lenses is more pronounced at low spatial frequencies than at mid-to-high spatial frequencies, indicating a trend where low spatial frequencies are unfavorable for myopia control, while mid-to-high spatial frequencies are favorable. In natural scenes, mid-to-high spatial frequency components are abundant, while low spatial frequency components are scarce. Compared to natural scenes, urban environments, especially indoors, are increasingly rich in low spatial frequency content, which may be a contributing factor to myopia development.

[0005] Furthermore, research indicates that the focal length variation curve of peripheral retinal images is another important pathway regulating ocular refractive development. The focusing ability of the human eye is inversely proportional to the object distance. In outdoor environments, objects are typically far from the eye, and the focal length variation of different parts of the surrounding environment image on the retina is minimal. In contrast, indoor environments are typically closer to the eye, and the focal length variation range of the surrounding environment image on the retina is much greater than when viewing distant objects. For example, when viewing images with object distances between 2.5 and 3 meters, the corresponding focal length variation range is 0.4D - 0.3D = 0.1D; when viewing images with object distances between 0.5 and 1 meter, the corresponding focal length variation range is 2D - 1D = 1D. A depth-sensing camera is used to capture 3D images of near-field learning environments from a perspective simulating the human eye. Using the distance from the camera to the textbook as the reference focal length, objects beyond the working distance will exhibit myopic defocus, while objects closer will exhibit hyperopic defocus. Experimental results show that the greater the fluctuation of the focal length change curve in the 30° visual field at the center of the retina and the higher the degree of hyperopic defocus in the para-central region of the retina, the faster the myopia progression. However, frame lenses based on peripheral blurring can control the axial length and myopia growth in myopic children (reducing it by 59%-74%) by lowering the contrast of the peripheral retinal image. This reduction in myopia progression may be achieved by disrupting the rapid changes in the focal length curve in the near-field working environment. While using lenses to construct form-based myopic defocus for myopia control has achieved good clinical results, this technology can affect visual acuity during application. A defocus signal for display image-longitudinal chromatic aberration (DI-LCA) is generated by altering the spectral power distribution (SPD) of the displayed image. This defocus signal only changes the proportions of red, green, and blue color signals in the image, without altering form-based characteristics such as contrast and spatial frequency distribution. The aim is to reduce the impact of optical lens defocus on visual acuity while regulating the refractive development of the eyeball.

[0006] However, the mechanisms by which changes in distance and lighting lead to myopia are still unclear, hindering in-depth research into the mechanisms by which the visual environment regulates refractive development. Summary of the Invention

[0007] To address the lack of clarity regarding the mechanisms by which the current visual environment influences refractive development, this application provides a method for detecting the effect of longitudinal chromatic aberration (DI-LCA) defocus signals on ocular refractive development. This method can analyze the role of DI-LCA defocus signals in regulating refractive development through cone cells at the tissue, animal, and molecular levels, providing support for the development of display drivers and devices that reduce the risk of myopia.

[0008] On the one hand, a method for detecting the effect of longitudinal chromatic aberration defocus signal on ocular refractive development is provided, the method comprising:

[0009] Obtain the spectral sensitivity function of human eye cone cells;

[0010] The first target defocus signal is obtained based on the spectral sensitivity function;

[0011] An experiment was conducted on the effect of the longitudinal color difference defocus signal of the displayed image on the human eye based on the spectral sensitivity function, and the second target defocus signal was obtained.

[0012] Animal-level in vivo detection experiments were conducted based on the spectral sensitivity function to obtain the defocus signal of the third target.

[0013] Based on the in vivo detection experiment, a molecular-level analysis experiment was conducted to investigate the effect of longitudinal chromatic aberration defocus signal of images on ocular refractive development.

[0014] The beneficial effects of the technical solution provided in this application include at least the following: This invention provides a method for detecting the effect of longitudinal chromatic aberration defocus signal on ocular refractive development. The method includes obtaining the spectral sensitivity function of human eye cone cells; obtaining a first target defocus signal based on the spectral sensitivity function; conducting an experiment on the effect of the longitudinal chromatic aberration defocus signal of a displayed image on the human eye based on the spectral sensitivity function to obtain a second target defocus signal; conducting an in vivo detection experiment at the animal level based on the spectral sensitivity function to obtain a third target defocus signal; and conducting a molecular-level analysis experiment on the effect of the longitudinal chromatic aberration defocus signal on ocular refractive development based on the in vivo detection experiment. The method provided by this invention can analyze the effect of DI-LCA defocus signal on refractive development through cone cells at the tissue, animal, and molecular levels, and optimize the target defocus signal, providing support for the development of display drivers and devices that reduce the risk of myopia. Attached Figure Description

[0015] To more clearly illustrate the technical solutions in the embodiments of this application, the accompanying drawings used in the description of the embodiments will be briefly introduced below. Obviously, the accompanying drawings described below are only some embodiments of this application. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0016] Figure 1 This illustration shows a schematic flowchart of an exemplary embodiment of the present application for detecting the effect of longitudinal chromatic aberration defocus signal on ocular refractive development;

[0017] Figure 2This illustration shows a schematic diagram of the recording of amplitude and latency in a full-field ERG detection method for detecting the effect of longitudinal chromatic aberration defocus signal on ocular refractive development, provided in an exemplary embodiment of this application.

[0018] Figure 3 This illustration shows a schematic diagram of the recording of amplitude and latency in an S-cone ERG examination during a method for detecting the effect of longitudinal chromatic aberration defocus signal on ocular refractive development, provided in an exemplary embodiment of this application.

[0019] Figure 4 This illustration shows a schematic diagram of the principle of a virtual telescope display in a method for detecting the effect of longitudinal chromatic aberration defocus signal on ocular refractive development, provided in an exemplary embodiment of this application.

[0020] Figure 5 This illustration shows another implementation flow diagram of a method for detecting the effect of longitudinal chromatic aberration defocus signal on ocular refractive development, provided in an exemplary embodiment of this application.

[0021] Figure 6 This illustration shows another implementation flow diagram of a method for detecting the effect of longitudinal chromatic aberration defocus signal on ocular refractive development, provided by an exemplary embodiment of this application. Detailed Implementation

[0022] To make the objectives, technical solutions, and advantages of this application clearer, the embodiments of this application will be described in further detail below with reference to the accompanying drawings.

[0023] The method provided in this invention develops the DI-LCA defocus signal into a display driver program, observes changes in the electroretinogram signal (ERG) of human eye cone cells to reveal the mediating pathway, clarifies the dose-response relationship through experiments, and further elucidates the molecular mechanism regulating refractive development and the mechanism by which the eye environment regulates refractive development.

[0024] Example 1

[0025] Figure 1 This diagram illustrates the implementation flow of a method for detecting the effect of longitudinal chromatic aberration defocus signal on ocular refractive development, as provided in an embodiment of the present invention.

[0026] See Figure 1 The detection method for the effect of longitudinal chromatic aberration defocus signal on ocular refractive development provided in this embodiment of the invention studies the effect and mechanism of DI-LCA defocus signal on refractive development at the tissue, animal and molecular levels, and may include steps 101 to 105.

[0027] Step 101: Obtain the spectral sensitivity function (SSF) of human eye cone cells.

[0028] Specifically, before obtaining the spectral sensitivity function, this method also includes observing the effects of different types and intensities of chromatic aberration defocus signals on the ERG signal to confirm the mediating pathway of defocus signals on refractive development.

[0029] First, based on the theory of photon correlation, a mathematical model was established to quantitatively express the stimulation intensity of three types of cone cells (S (short-wavelength), M (medium-wavelength), and L (long-wavelength) in the human eye by form and color vision stimulation signals. Using VR technology, reducing the stimulation signal of S-cone cells and increasing the stimulation signals of M-cone cells and L-cone cells in the displayed image can inhibit refractive development. Based on these phenomena, a hypothesis of refractive development regulation driven by the longitudinal chromatic aberration (DI-LCA) defocus signal of the displayed image is proposed. That is, increasing the ratio of photon intensity perceived by S-cone cells to M+L-cone cells can stimulate refractive development, while decreasing this ratio can inhibit it.

[0030] In some embodiments, adjusting the SPD of the displayed image alters the photon intensity perceived by the S and M+L cone cells, generating different DI-LCA defocus signals and modulating refractive development. Increasing the photon intensity perceived by the S cone cells and decreasing the photon intensity perceived by the M+L cone cells in the displayed image are identified as hyperopic LCA defocus signals, promoting refractive development and inducing myopia; conversely, decreasing these signals are identified as myopic LCA defocus signals, inhibiting refractive development and suppressing myopia. Furthermore, the ratio of the perceived photon intensities of S to M+L (referred to as the S / (M+L) ratio) can be used to predict the modulating effect of the DI-LCA defocus signal; an increased S / (M+L) ratio promotes refractive development, while a decreased ratio inhibits it.

[0031] The process by which the spectral sensitivity function of cone cells in the human eye regulates refractive development through the input image (visual environment) mainly involves three steps: focusing by the refractive system, sensing photon intensity by cone cells, and generating a regulatory cascade signal by the PRE / choroid / sclera. Studies show that regulation can be limited to the retina rather than necessarily involving the visual cortex. The image signals that regulate refractive development, such as image contrast and color, are all subjectively perceived signals after processing by the visual cortex. Only defocused signals are subjectively indistinguishable. This invention analyzes the regulatory mechanism of localized eye development in the retina, independent of the visual cortex, based on signals processed by the visual cortex.

[0032] In some embodiments, the formula for calculating the photon intensity sensed by cone cells, i.e., the spectral sensitivity function of human eye cone cells, includes:

[0033] R=∫Φ(λ)f(λ)dλ

[0034] Where R is the photon intensity perceived by the cone cells, λ is the wavelength, Φ(λ) is the spectral power distribution (SPD) of the displayed image, and f(λ) is the absorption of light of different wavelengths by the cone cells.

[0035] In a specific example, the process of constructing an SFF function may include the following steps:

[0036] The area of ​​the light spot formed by various wavelengths of light from a specific SPD point light source after passing through the human eye's refractive system at infinity is calculated at 5nm intervals. The optical power is converted into incident photon intensity, and the perceptible photon intensity for each wavelength of light by S, M, and L cone cells is calculated by weighting the light spot area and the absorption rate of cone cells for different wavelengths. The perceptible photon intensities corresponding to all wavelengths are superimposed to obtain the perceptible photon intensity (perceptible photon point spread function) of S, M, and L cone cells for a specific SPD point light source. Based on the spatial distribution of S, M, and L cone cells on the retina, the perceptible photon point spread function is used to generate curves showing the absolute value of the photon intensity perceived by S, M, and L cone cells and the S / (M+L) ratio under different visual environments.

[0037] Step 102: Obtain the first target defocus signal based on the spectral sensitivity function.

[0038] In some embodiments, step 102 includes:

[0039] Based on the spectral sensitivity function, adjust the longitudinal color difference defocus signal of the displayed image;

[0040] The vertical color difference defocus signal of the display image that can meet the first preset condition is selected as the first target defocus signal;

[0041] The first target defocus signal is a longitudinal chromatic aberration defocus signal of a myopic display image that can cause a decrease in photon intensity perceived by short-wavelength cone cells and an increase in photon intensity perceived by mid-wavelength and long-wavelength cone cells.

[0042] Based on the SFF function provided in this embodiment of the invention, the changes in the S / (M+L) ratio before and after wearing dotted defocus lenses and diffuse lenses were simulated and calculated under different viewing distances, different refractive correction states, different illumination spectra, different illumination brightness, and different viewing distances. The results show that distance viewing, full correction, narrow bandwidth long wavelength illumination (650nm), high illumination brightness, and wearing dotted defocus lenses and diffuse lenses all reduce the S / (M+L) ratio, which is beneficial for controlling myopia. Near viewing, low illumination brightness, overcorrection of the central retina, and undercorrection all lead to an increase in the S / (M+L) ratio, which is detrimental to controlling myopia.

[0043] Furthermore, based on the human eye cone cell SSF model, by changing the SPD of the displayed image, a myopic DI-LCA defocus signal can be set that causes a decrease in photon intensity perceived by S cells and an increase in photon intensity perceived by M and L cells.

[0044] In a specific example, experiments were conducted based on the aforementioned DI-LCA defocus signal. Adults who watched videos containing myopic DI-LCA defocus signals for 2 hours showed a significant reduction in the myopic trend in refractive error, choroidal thickness, and axial length. In children, a 24-week observation period following viewing videos containing myopic DI-LCA defocus signals showed that the signal could slow the increase in refractive error and axial length; children in the 2-hour daily viewing group showed a trend of cessation in refractive error growth. These results suggest that modifying the SPD of the displayed image to create myopic DI-LCA defocus signals has the potential to control myopia.

[0045] The human eye cone cell spectral sensitivity function provided in this embodiment of the invention can be used to describe the photon intensity signal formed locally on the retina by the incoming image and the visual environment and perceived by the cone cells, so as to conduct a more direct analysis of the mechanism by which the incoming image and the visual environment regulate refractive development.

[0046] Based on the above model, the photons perceived by cone cells are the physical essence of the modulating signal, and the photons are used as the basic unit to mathematically describe the form and color vision stimuli. Specifically, the above model and indicators can predict the trends of refractive development under different form (viewing distance, refractive correction state, dot defocus lenses, and diffuse lenses) and color (light source spectrum, illumination brightness) stimuli. Furthermore, a myopic longitudinal chromatic aberration defocus signal that causes a decrease in the ratio of photon intensity perceived by S / (M+L) cone cells can be constructed. Preliminary clinical results show that this signal can inhibit the occurrence of myopia without changing image sharpness.

[0047] In some embodiments, the effects of applying different stimuli to different cone cells were analyzed based on the red-green dual-color balance experiment. The red-green dual-color balance experiment is a method for precisely adjusting the spherical lens based on the LCA principle. When adjusting the spherical lens using 0.25D interval lenses, the red-green balance rate was less than 20%, while adjusting the interval to 0.05D increased the red-green balance rate to over 80%45,46. The rate of myopia progression in adolescents and children wearing 0.05D interval, fully corrected red-green balanced lenses was significantly slower than that in the group wearing 0.25D interval, undercorrected red-green balanced lenses. Furthermore, in the experiment, the myopia of children wearing 0.05D interval, fully corrected red-green balanced lenses increased by -0.09±0.08D after 6 months, while the myopia of children wearing 0.25D interval, undercorrected red-green balanced lenses increased by -0.18±0.06D after 6 months. Studies have shown that when red-green light is in balance, the 570nm wavelength light falls precisely on the retina, while the absorption peak wavelength of the L-cones in the human eye is around 565nm. This allows the image to maximize the signal generated by the L-cones. In red-green undercorrection, the 620nm wavelength red light focuses on the retina, but this wavelength is far from the absorption peak wavelength of the L-cones, thus preventing the image from stimulating them to produce the maximum signal. Therefore, it can be inferred that the reason full correction is beneficial for myopia control is that the enhanced signal stimulation of the L-cones during full correction reduces the signal intensity ratio between the S-cones and L-cones.

[0048] Step 103: Based on the spectral sensitivity function, conduct an experiment on the effect of the longitudinal color difference defocus signal of the displayed image on the human eye to obtain the second target defocus signal.

[0049] Specifically, at the tissue level, we observed changes in ERG signals related to cone cells on the retina when the human eye viewed different types and intensities of DI-LCA defocused signals to confirm the mediating pathway.

[0050] In some embodiments, step 103 includes:

[0051] Select the first number of volunteers;

[0052] After stimulation by the longitudinal chromatic aberration defocus signal of the displayed image, the volunteers underwent electroretinography (ERG) signal examination and ocular biological examination, respectively. The ERG signal examination included full-field ERG signal examination, short-wavelength ERG signal examination, and multifocal ERG signal examination.

[0053] The defocus signal of the second target is obtained based on the inspection results.

[0054] In a specific example, based on the previously established human eye cone cell SSF model, different types and intensities of DI-LCA defocus signals were designed for both hyperopic and myopic individuals. The time-domain and frequency-domain ERG signals, as well as ocular biological parameters, were recorded when the human eye viewed these different types and intensities of DI-LCA defocus signals. Optionally, ocular biological parameters may include, but are not limited to, changes in axial length and choroidal thickness.

[0055] Based on the response of cone cells to different types and intensities of DI-LCA defocus signals, this study clarifies the recognition of defocus signals by cone cells, confirms that the sensory pathway for defocus signals is the cone cell, and optimizes the DI-LCA defocus signal by comparing the intensity of ERG signals and the magnitude of changes in biological parameters.

[0056] Through multiple sets of experiments, myopic DI-LCA defocus signals that inhibit S cone cells and stimulate M and L cone cells, and hyperopic DI-LCA defocus signals that stimulate S cone cells and inhibit M and L cone cells were selected.

[0057] Furthermore, while ensuring the effect of inhibiting the refractive development of the eyeball, the DI-LCA defocus signal intensity with the least impact on image quality is selected.

[0058] In a specific example, the functional detection process is as follows.

[0059] First, the study participants were determined. Optional recruitment was conducted, with 20 volunteers aged 8-17, 18-25, and 26-45. Inclusion criteria were as follows: best correction of 1.0 or better, astigmatism less than or equal to 1.00D, normal color vision, and healthy eyes. Exclusion criteria included any ocular pathology, any known systemic disease, or a history of epilepsy.

[0060] Perform a full-field ERG examination on the ocular subject. Optionally, use the full-field clinical ERG examination procedure published by the International Society for Clinical Electrophysiology of Vision (ISCEV) in 2022, the results of which mainly reflect the response of M and L cone cells to DI-LCA defocus signals.

[0061] Figure 2 This diagram illustrates the recording of amplitude and latency in full-field ERG detection provided by an embodiment of the present invention.

[0062] Specifically, the background brightness is set to 30 cd / m², and the applicable time is 10 minutes; the stimulation flash wavelengths are set to the original stimulation flash (LED composite white light), the center wavelength of the myopic DI-LCA defocus signal, and the center wavelength of the hyperopic DI-LCA defocus signal; the stimulation flash intensity is 3 cd / m²; the flash duration is 5 ms; the flash frequency of the LA 3ERG signal is 2 Hz, and the flash frequency of the LA30Hz ERG signal is 30 Hz. Both the LA 30Hz ERG and LA 3ERG signals originate from bipolar cells; the former mainly reflects the function of M and L cone cells, while the latter reflects the function of S, M, and L cone cells.

[0063] Perform an S-cone ERG examination on the eyeball. Optionally, use the S-cone ERG examination procedure published by ISCEV 2020, the results of which primarily reflect the response of S cone cells to DI-LCA defocus signals.

[0064] Figure 3 This diagram illustrates the recording of amplitude and latency in an S-cone ERG test provided by an embodiment of the present invention.

[0065] Specifically, after recording the ERG patterns of the M and L cones, the patient was first acclimatized for 10 minutes under white light at an intensity of 30 cd / m², following the ISCEV procedure, and then an S-cone ERG examination was performed. The background light center wavelength was controlled at 570-620 nm, and the background brightness was set to 300 cd / m². The stimulation flash wavelengths were set as follows: original stimulation flash (center wavelength between 450 and 470 nm), center wavelength of the myopic DI-LCA defocus signal, and center wavelength of the hyperopic DI-LCA defocus signal; stimulation flash intensities were: 0.005, 0.009, 0.014, 0.017, 0.022, 0.027, 0.037, 0.045, 0.057, 0.072, 0.091, and 0.118 cd / m²; the flash duration was 5 ms, and the flash frequency was 2 Hz. The signal from the S-cone ERG examination mainly originated from the S cone cells.

[0066] Perform mf-ERG examination on the eyeball. Optionally, use the mf-ER examination procedure released by ISCEV 2021, the results of which mainly reflect the response of cone cells in different locations to DI-LCA defocus signals.

[0067] Specifically, the LCA defocus mf-ERG test stimulus target array consisted of 103 unscaled hexagons displayed on a 22-inch color LCD monitor. The intensity of the blue, green, and red color signals on the monitor could be adjusted separately. Researchers generated six different DI-LCA defocus signals for myopia and hyperopia by adjusting the intensity of the three color signals. During the mf-ERG test, the screen distance from the eye was 67 cm, and the stimulus target array was 29° horizontally and 24° vertically. The mf-ERG device used was VERIS Science 6.0 (Electro-Diagnostic Imaging Inc., SanMateo, CA, USA). The stimulus sequence consisted of a multifocal flash frame, a dark frame, a full-screen global flash, and a dark frame in each cycle. Each hexagonal stimulus target transitioned between bright and dark according to a pseudo-random binary sequence at a rate of 75 Hz. One eye of the subject was randomly selected to record the mf-ERG pattern. Before the measurement began, tropicamide was instilled twice every 5 minutes to dilate the pupil to 7mm, and the contralateral eye was covered with an eye patch. The room brightness during the examination was approximately 240 Lux. MF-ERG images were recorded in random sequence under six different DI-LCA defocus signals, with each signal taking approximately 10 minutes to process. The macula was divided into six concentric circles with radii of 1.3°, 3.9°, 6.5°, 9.1°, 11.7°, and 14.3°. The amplitude and latency of the direct and induced ERG signals in each region were calculated.

[0068] Frequency domain analysis was performed on the inspection results of the above ERG signals.

[0069] Specifically, the changes caused by different DI-LCA defocusing signals are identified by examining the frequency components of the ERG amplitude signal. The ERG signal is converted into a series of sine waves of different frequencies using the Fast Fourier Transform (FFT) program in MATLAB. The frequency domain of the ERG signal is specifically described as follows:

[0070]

[0071] X(f) is the signal in the frequency domain, and x(t) is the signal in the time domain.

[0072] Furthermore, the method provided in this embodiment of the invention also includes ocular biological measurements.

[0073] Specifically, the eye is measured separately using an ocular biological measurement instrument and an OCT according to the standard operating procedures of the equipment. Parameters such as axial length, corneal curvature, anterior chamber depth, corneal diameter, and choroidal thickness are recorded, and the model of the examination instrument is registered.

[0074] Step 104: Conduct an in vivo detection experiment at the animal level based on the spectral sensitivity function to obtain the defocus signal of the third target.

[0075] Specifically, in vivo validation at the animal level will be conducted. The effects of different types and intensities of chromatic aberration defocus signals on the refractive power and axial length development of experimental animals will be verified to reveal the dose-response relationship.

[0076] In some embodiments, step 104 includes:

[0077] A second number of tree shrews were selected and divided into a third number of tree shrew rearing groups; the second number was greater than the third number.

[0078] The tree shrew rearing group was fed based on different visual spaces, different types of defocused signals, and different intensities of defocused signals.

[0079] The defocus signal of the third target was obtained based on the detection experiment of the tree shrew after feeding.

[0080] The tree shrew rearing group includes a virtual telescope enclosure;

[0081] The rearing conditions of the virtual telescope enclosure include setting up a virtual telescope display, which is used to project a virtual image at a first distance and a second imaging distance, wherein the first distance is smaller than the second imaging distance.

[0082] Optionally, the first imaging distance is 30cm, and the second imaging distance is 3m.

[0083] In some embodiments, step 104 includes raising tree shrews in an indoor near-field visual environment and setting up a virtual telescopic display module. The effects of different types and intensities of DI-LCA defocus signals on the refractive power and axial growth of the tree shrew's eyes are observed at different visual distances (far-field, near-field, and virtual far-field) to determine the dose-response relationship.

[0084] In a specific example, the experimental procedure for the effect of LCA defocused rearing environment on the refractive development of tree shrews is as follows.

[0085] Tree shrews were chosen as the research subject. Tree shrews are small, diurnal mammals whose refractive system development direction and speed under different wavelengths of light are more similar to those of monkeys, showing significant differences compared to animals like guinea pigs and chicks. Tree shrews are born with their eyes closed. Around three weeks old, their eyes open within a few days. The first day their eyes are open is defined as the Day of Experience (DVE). The applicant plans to conduct experiments on tree shrews at 24 DVE and 36 DVE. Tree shrews at 24 DVE are in their developmental stage, with a slightly farsighted refractive state, making them highly sensitive to visual stimuli, similar to the eyes of pre-pubescent humans. Tree shrews at 36 DVE have a relatively stable refractive state after development, similar to the eyes of post-pubescent humans.

[0086] Tree shrews were raised in different visual spaces (far distance, near distance, virtual far distance), with different DI-LCA defocus signal types (myopic, hyperopic), and with different DI-LCA defocus signal intensities.

[0087] Table 1 shows the grouping of the rearing environments for tree shrews.

[0088] Table 1

[0089]

[0090]

[0091] Specifically, in the normal open group, tree shrews live in enclosures with open mesh openings at the front and top, allowing them to see a wide view of the external environment from these two positions. During the day, the lighting in the enclosure is maintained at 200-300 lux.

[0092] In the near-field vision group, tree shrews were housed in opaque enclosures with sides of 30cm, theoretically simulating a near-field learning environment with a visual range of 30-42cm. Ventilation holes were provided in the top lid for placing water bottles and food, but the tree shrews could not see the outside environment through these holes. A 26cm wide and 15cm high opening was made in the front wall of the enclosure, where a 10-inch LCD screen was fixed, displaying a white background with a black Maltese cross. The intensity of the blue, green, and red signals on the screen could be adjusted individually. Researchers generated six different DI-LCA defocus signals of varying intensities for myopia and hyperopia by adjusting the intensity of these three color signals. A diffused lighting system was installed at the top of the enclosure to ensure that the daytime brightness inside the enclosure was the same as that of the normal open group.

[0093] Figure 4 A schematic diagram illustrating the principle of the virtual telescope display provided in an embodiment of the present invention is shown.

[0094] The virtual telescope enclosure replaced the 10-inch LCD monitor with a virtual telescope monitor previously built by the applicant. This monitor, based on a coaxial catadioptric freeform surface optics scheme, can project a virtual image with an imaging distance of over 3 meters from a distance of 30cm, thus allowing the viewer's eye accommodation to relax and avoiding environmental factors that could induce myopia. Other environmental parameters within the enclosure remained consistent with those of the near-vision group.

[0095] Furthermore, the tree shrews were fed and tested.

[0096] Specifically, starting from day 24 of the first day of gestation (DVE), the tree shrews were housed in separate enclosures in groups for 12 days. Except for the normally open group, the other groups were kept away from the external environment as much as possible during the rearing process. On days 0, 2, 4, 6, 8, 10, and 12, the refractive error and axial length of the tree shrews were measured using a computerized refractometer and a biometer. Measurements were taken between 10 and 11 AM, with the ambient light level below 10 lux.

[0097] In some embodiments, the method provided by the present invention further includes:

[0098] The optimal target defocus signal is calculated based on the first target defocus signal, the second target defocus signal, and the third target defocus signal.

[0099] The embodiments of the present invention can optimize the longitudinal chromatic aberration defocus signal of the displayed image based on the above experimental process, so as to effectively intervene in the refractive development process.

[0100] Step 105: Based on the in vivo detection experiment, conduct a molecular-level analysis experiment on the effect of the longitudinal chromatic aberration defocus signal of the image on the refractive development of the eyeball.

[0101] Specifically, we will conduct molecular-level analysis of the influencing mechanisms. We will analyze the effects of different chromatic aberration defocus signals on the gene sequences related to the retinal-RPE / choroid-scleral cascade signal to explore the regulatory mechanisms.

[0102] In some embodiments, step 105 includes:

[0103] For each of the tree shrew rearing groups, the effects of different display images on the longitudinal chromatic aberration defocus signal on the mRNA levels of candidate genes in the retina, retinal pigment epidermis, and sclera were detected.

[0104] For each of the tree shrew feeding groups, changes in retinal dopamine, 3,4-dihydroxyphenylacetic acid (DPA) levels, and the DPA / 3,4-dihydroxyphenylacetic acid ratio were measured.

[0105] The changes in the mRNA levels of candidate genes in the retina, retinal pigment epidermis (RPE), and sclera of tree shrews under different visual growth environments were detected using quantitative PCR. Further analysis was conducted to determine whether the DI-LCA defocus signal regulates ocular refractive development through a cascade of signals similar to or the same as those used in optical lens defocusing and form deprivation.

[0106] Specifically, the protein products corresponding to candidate genes mainly fall into four categories: cell surface interactions (DRD1 / 2, CTG, BMP2, GJA1, LRP2, etc.), intracellular signal transduction (DBH, NOS, TYR, etc.), transcriptional regulation (EGR1, FOS, EGR1, etc.), and protein secretion (CTGF, FGF10, IL18, SST, IGF2, VIP, etc.).

[0107] By measuring changes in retinal dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) levels and the retinal DOPAC / DA ratio, as well as the expression of candidate genes, the effects of DI-LCA defocus signal on the ocular emmetropization regulatory cascade signals in three stages and locations: retina, RPE / choroid, and sclera were determined.

[0108] In a specific instance, further verification is performed based on tree shrews.

[0109] Specifically, after the intervention, the tree shrew was euthanized and both eyes were removed. The vitreous body, retina, retinopathy of prematurity (RPE), and sclera were removed under a surgical microscope. The vitreous body was immediately frozen in liquid nitrogen. The retina and RPE mixture was rinsed in ice-cold sterile PBS to remove residual RNA, then transferred to fresh PBS and placed on ice for approximately 20 minutes, occasionally gently agitated to separate the RPE from the retina. The retina and sclera were frozen in liquid nitrogen. The suspended RPE fragments were centrifuged, the supernatant was removed, and the mixture was immediately processed to separate RNA. Retinal and vitreous samples for high-performance liquid chromatography (HPLC) were homogenized in phosphate-buffered saline containing 0.1 mM EDTA, and the homogenate was centrifuged at 6000 rpm for 10 minutes at 4°C. The supernatant was combined with an equal volume of perchloric acid and centrifuged at 20000 rpm for 10 minutes at 4°C. The supernatant was then collected and analyzed.

[0110] Furthermore, quantitative PCR primers for candidate genes were designed using Beacon Designer v7.7 (Premier Biosoft International, Palo Alto, CA) following the method of Norton et al. (2018). The qPCR cycling parameters were as follows: initial denaturation at 95°C for 10 minutes, followed by 40 cycles at 95°C for 15 seconds and 62°C for 60 seconds. Relative gene expression levels were calculated using the method of Livak et al. (2001). First, the expression levels of target genes were normalized to the expression levels of internal reference genes, and then the relative expression levels of target genes in each intervention group and control group were compared.

[0111] On the other hand, the concentrations of dopamine and DOPAC were determined by comparing the peak areas of the samples with those of the standards using Chromeleon 7 chromatographic data system software (Thermo Fisher Scientific). Each compound in the standard solutions showed high correlation and good reproducibility. The detection resolution was <1 pg.

[0112] The above experimental process shows that cone signals can sense defocus signals, and different types and intensities of defocus signals can have different effects on the latency and amplitude of EGR signals. Further analysis will be conducted to determine whether myopic and hyperopic DO-LCA defocus signals can respectively inhibit or stimulate the refractive development of the eye, and to clarify whether there is a dose-response relationship between signal strength and eye refractive development.

[0113] The method provided in this invention can establish a correlation between myopic and hyperopic DI-LCA defocus signals and known cascade signal systems regulating ocular refractive development. By utilizing changes in molecular marker expression and DA-related parameters, it can identify possible mechanisms by which DI-LCA defocus signals regulate ocular refractive development.

[0114] This invention provides a human eye cone cell SSF model, establishing a hypothesis that DI-LCA defocus signal regulates refractive development. It uses photons from quantum physics as the basic unit to mathematically describe the DI-LCA defocus signal, further using it to predict biological phenomena regulating eye refractive development. Based on simply changing the SPD information of an image, eye refractive development can be regulated without altering form perception or affecting image clarity. This invention proposes that the ratio of photon intensities perceived by S and M+L cone cells is a key signal for DI-LCA defocus signal regulation of refractive development, and also serves as a bridge for signal transmission between image color perception information and refractive development. Furthermore, this invention incorporates Fourier transform into the analysis of the impact of DI-LCA defocus signal on ERG signal, thereby expanding the amplitude of ERG changes under different DI-LCA defocus signals. Further, combined with biofeedback technology, the DI-LCA defocus signal is optimized and improved based on changes in the ERG signal, enhancing its effectiveness.

[0115] The detection method for the effect of longitudinal color difference defocus signal on ocular refractive development provided by the embodiments of the present invention can, on the one hand, provide a quantitative analysis tool for basic research on the regulation of refractive development by the eye use environment, and on the other hand, provide theoretical support for the development of display drivers and devices that reduce the risk of myopia, and provide new ideas for solving the clinical problem of myopia induced by close-range use of eyes in adolescents and children indoors.

[0116] Example 2

[0117] DI-LCA defocus signals can alter the rate of refractive development of the eye, producing results similar to lens defocus. From a physics perspective, both optical lens defocus and DI-LCA defocus lead to changes in the photon intensity sensed by cone cells. When different methods of regulating refractive development are incorporated into the SSF model of human cone cells, the model's predictions are consistent with clinical observations, indicating that photons are the physical essence of signals regulating eye development, such as optical lens defocus and DI-LCA defocus.

[0118] Furthermore, embodiments of the present invention can further verify whether photons need to reach frequency thresholds, intensity thresholds, and proportion thresholds before they can induce changes in retinal electrical signals, and establish a mathematical model between DI-LCA defocus signals and cone cell EGG signals by referring to the photoelectric effect formula of metals.

[0119] Figure 5 This illustration shows another implementation flowchart of the method for detecting the effect of longitudinal chromatic aberration defocus signal on ocular refractive development provided in an embodiment of the present invention.

[0120] See Figure 5In a specific example, the construction process of the human eye cone cell spectral sensitivity function model in the method provided by this embodiment of the invention includes theoretical verification of factors that accelerate and inhibit refractive development. Factors that accelerate refractive development include, but are not limited to, near vision, low illumination brightness, and undercorrection or overcorrection of the central retina lens; factors that inhibit refractive development include, but are not limited to, distant vision, full correction of the important retina, narrow bandwidth long wavelength illumination, point defocus lenses, and scattering lenses. Factors that accelerate refractive development are associated with an increase in the S / (M+L) ratio, while factors that inhibit refractive development are associated with a decrease in the S / (M+L) ratio.

[0121] Furthermore, preliminary clinical validation was conducted to establish the unidirectional modulation effect of myopic DI-LCA defocus signal based on factors influencing refractive development. The validation showed that when glasses were prescribed at 5-degree intervals for full correction, the rate of myopia progression was slower than when prescriptions were prescribed at 25-degree intervals; reducing S-cell stimulation signals and increasing M and L-cell stimulation signals were more beneficial for increasing choroidal thickness; and long-term exposure to M and L-cell stimulation signals was more beneficial for controlling axial elongation in children.

[0122] Figure 6 This illustration shows another implementation flowchart of the method for detecting the effect of longitudinal chromatic aberration defocus signal on ocular refractive development provided in an embodiment of the present invention.

[0123] See Figure 6 In a specific example, the method provided by this invention can be used to explore the bidirectional modulation effect of DI-LCA defocus signals in myopia and hyperopia.

[0124] The method for detecting the effect of longitudinal chromatic aberration defocus signal on ocular refractive development provided in this embodiment of the invention may include the following steps.

[0125] Functional observations at the tissue level and in vivo verification at the animal level were conducted separately.

[0126] Tissue-level functional observation includes designing LCA defocus signals of different types and intensities, acquiring corresponding EGR signals and ocular biological parameters, and comparing the similarities and differences of EGR signals and ocular biological parameters in each group.

[0127] Animal-level in vivo verification included setting up a tree shrew rearing environment, raising tree shrews in different visual spaces and under LCA defocus signals, and comparing the similarities and differences in axial length and refractive power development among different groups of tree shrews.

[0128] Furthermore, in vivo validation at the animal level was used to analyze the molecular mechanisms, including isolating retinal, RPE, and scleral tissues from tree shrews raised under different morphological spaces and LCA defocus signals. Quantitative PCR was performed on the isolated tissues to compare the differences in candidate gene mRNA levels among the groups; high-performance liquid chromatography (HPLC) was also used to compare changes in retinal dopamine (DA)-related parameters among the groups.

[0129] Based on the above experimental steps, this study elucidates the role and possible mechanism of longitudinal chromatic aberration defocus signal in regulating ocular refractive development under indoor near-field vision conditions.

[0130] In summary, the detection method for the effect of longitudinal chromatic aberration defocus signal on ocular refractive development provided in this embodiment of the invention starts from the clinical phenomenon that small-amplitude optical lens defocus changes cause significant changes in the speed of refractive development. Through optical modeling, a possible refractive development regulation signal - LCA - is discovered. Further analysis using the human eye cone cell SSF model reveals that after the same image is illuminated on the retina by a small-amplitude overcorrected and undercorrected optical system, the ratio of photon intensities perceived by S cones, M cones, and L cones will change significantly, and the magnitude is much greater than the impact of overcorrection and undercorrection on image clarity.

[0131] This invention employs a human eye cone cell SSF model to design myopic and hyperopic DI-LCA defocus signals. By substituting methods that promote and inhibit refractive development into the model, it was determined that methods promoting refractive development all produce hyperopic LCA defocus signals, while methods inhibiting refractive development all produce myopic LCA defocus signals. The detection method for the longitudinal chromatic aberration defocus signal's effect on ocular refractive development provided by this invention can analyze the role of DI-LCA defocus signal in regulating refractive development through cone cells at the tissue, animal, and molecular levels. It explores the molecular mechanism of DI-LCA defocus signal regulating refractive development at the local level, elucidating the function and upstream and downstream signal regulation mechanism of the DI-LCA defocus-cone cell-dopamine signal axis in ocular refractive development.

[0132] The above-described embodiments are only used to illustrate the technical solutions of the present invention, and are not intended to limit it. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some of the technical features. Such modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of the present invention, and should all be included within the protection scope of the present invention.

Claims

1. A method for detecting the effect of longitudinal chromatic aberration defocus signal on ocular refractive development, characterized in that, The method includes: Obtain the spectral sensitivity function of human eye cone cells; The first target defocus signal is obtained based on the spectral sensitivity function; An experiment was conducted on the effect of the longitudinal color difference defocus signal of the displayed image on the human eye based on the spectral sensitivity function, and the second target defocus signal was obtained. Animal-level in vivo detection experiments were conducted based on the spectral sensitivity function to obtain the defocus signal of the third target. Based on the in vivo detection experiment, a molecular-level analysis experiment was conducted on the effect of image longitudinal chromatic aberration defocus signal on ocular refractive development. The spectral sensitivity function of the human eye's cone cells includes: Where R is the photon intensity perceived by the cone cells. For wavelength, To display the spectral power distribution of the image, This represents the absorption of light of different wavelengths by cone cells; The step of obtaining the first target defocus signal based on the spectral sensitivity function includes: Based on the spectral sensitivity function, adjust the longitudinal chromatic aberration defocus signal of the displayed image; The vertical color difference defocus signal of the display image that can meet the first preset condition is selected as the first target defocus signal; The first target defocus signal is a longitudinal chromatic aberration defocus signal of a myopic display image that can cause a decrease in photon intensity perceived by short-wavelength cone cells and an increase in photon intensity perceived by mid-wavelength and long-wavelength cone cells. The optimal target defocus signal is calculated based on the first target defocus signal, the second target defocus signal, and the third target defocus signal.

2. The method according to claim 1, characterized in that, The experiment on the effect of the longitudinal color difference defocus signal of the displayed image on the human eye based on the spectral sensitivity function, and the acquisition of the second target defocus signal, includes: Select the first number of volunteers; After stimulation by the longitudinal chromatic aberration defocus signal of the displayed image, the volunteers underwent electroretinography (ERG) signal examination and ocular biological examination, respectively. The ERG signal examination included full-field ERG signal examination, short-wavelength ERG signal examination, and multifocal ERG signal examination. The defocus signal of the second target is obtained based on the inspection results.

3. The method according to claim 2, characterized in that, The step of obtaining the second target out-of-focus signal based on the inspection result includes: The electroretinogram (ERG) signal examination results are analyzed in the frequency domain to obtain the defocus signal of the second target.

4. The method according to claim 1, characterized in that, The in vivo detection experiment at the animal level based on the spectral sensitivity function, to obtain the defocus signal of the third target, includes: A second number of tree shrews were selected and divided into a third number of tree shrew rearing groups; the second number was greater than the third number. The tree shrew rearing groups were fed based on different visual spaces, different types of defocused signals, and different intensities of defocused signals. The defocus signal of the third target was obtained based on the detection experiment of the tree shrew after feeding.

5. The method according to claim 4, characterized in that, The tree shrew rearing group includes a virtual telescope enclosure; The rearing conditions of the virtual telescope enclosure include setting up a virtual telescope display, which is used to project a virtual image at a first distance and a second imaging distance, wherein the first distance is smaller than the second imaging distance.

6. The method according to claim 4, characterized in that, The molecular-level analysis experiment on the effect of longitudinal chromatic aberration defocus signal of images on ocular refractive development based on the in vivo detection experiment includes: For each of the tree shrew rearing groups, the effects of different display images' longitudinal chromatic aberration defocus signals on the mRNA levels of candidate genes in the retina, retinal pigment epidermis, and sclera were detected. For each of the tree shrew feeding groups, changes in retinal dopamine, 3,4-dihydroxyphenylacetic acid (DPA) levels, and the DPA / 3,4-dihydroxyphenylacetic acid ratio were measured.

7. The method according to claim 6, characterized in that, The protein products corresponding to the candidate genes include cell surface interactions, intracellular signal transduction, transcriptional regulation, and protein secretion.

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