一、 The mathematical principles, physical models and quantitative formulas of myopia prevention and control:
The global myopia rate is rising rapidly. The core reason is not to find the essence of the problem from the first principle, but to find the method from the environmental point of view. Through a large number of experiments, it is found that the existing mainstream methods do not introduce the two parameters of scleral elastic modulus and force. We analyze it from the perspective of sphere mechanics, covering environment and heredity, and study it in a purely mathematical model. The expression of hereditary genes is reflected in the elastic modulus of the sclera.
Centripetal Mechanics
We use sphere mechanics to start with the ciliary muscle
It is found that the target point of myopia is the junction of the longitudinal muscle and the sclera, and the target point of myopia is the circular scleral circle
Continuous close learning results in continuous loading of axial force and centripetal force on children’s targets
The round eyeball becomes ellipse by the centripetal force on the scleral ring (target point)
The centripetal force affects the axial length of the eyeball
How does the calculation sphere become an ellipse?
Verify the size of the force through the liquid lens model
Analyze the size of the force on the eyeball at different distances
Use behavior indicators to get close eye use time
Analyze the elastic modulus of sclera, E
We use partial calculus calculations to analyze the value of scleral curvature changes and true myopia, pseudo myopia, astigmatism, elastic modulus, plastic deformation, etc.
Scleral modulus of elasticity
Each age group, the elastic modulus of the sclera can be different
Analyze susceptibility genes and mechanisms
Children have soft sclera and low scleral elastic modulus; adults have hard sclera and high scleral elastic modulus. Myopia is related to genetic genes (HLA-DPB1), COL1A1 factor, and the content of leucan gene MRNA factor in human sclera tissue. During the formation of myopia, the vitreous body gradually splits with changes in the length of the eye axis. We assume that the role of inherited factors and hypoxia is reflected in the elastic modulus of the sclera. For people with genetic genes, the scleral collagen fibers are thin and the content is low, then The sclera is in a glued state, and the hardness is not enough. The scleral elastic modulus can be negatively correlated with genetic factors and age.
Scleral elastic modulus test method
Axial difference table for normal children (can be measured with a biometer)
Research results in constant (P)
In the process of researching the digital sclera, the formula for the difference of the ocular axis was obtained:
Myopia: (The deviation of the eye axis length (∆AL) is proportional to the time (t) and force (f) of the close learning, and inversely proportional to the scleral elastic modulus (E)), the learning time t cannot be reduced, But it can increase the scleral elastic modulus E, thereby reducing the development of myopia.
Analysis of the meaning of the eye axis difference formula:
∆AL is the difference between the eye axis length and the normal eye axis
f is force (mN)
t is the time to use eyes at close range
P is a constant
E is the scleral elastic modulus energy
L is the distance of close work
We found the core reason for the lengthening of the adolescent’s eye axis: when the scleral elastic modulus is lower than the threshold, continuous use of the eye at close distances causes the longitudinal muscles in the ciliary body to contract and spasm, and the centripetal force acting on the scleral eccentric ring suppresses the vertical diameter of the sclera. , So that the eye axis becomes longer. When the scleral elastic modulus is higher than the threshold, the continuous centripetal force has no effect on the scleral shape.
Mathematical model of sclera remodeling by optical feedback
In this study, a mathematical model to quantify the axial growth of the sclera was proposed: the centripetal force acting on the scleral circle and the adjustment amplitude formed by the action time and the elastic modulus of the sclera determine the extent of scleral remodeling. This model shows When the elastic modulus of the sclera is lower than the adjustment amplitude impulse, the axial growth of the sclera appears, and its growth rate is negatively correlated with the elastic modulus and positively correlated with the impulse. When zero pressure is established, the axial growth rate is zero. Properly increasing the elastic modulus of the sclera (thickening the collagen fibers of the sclera) is a way to control myopia. Through the study of centripetal force and scleral elastic modulus, after a lot of calculation and analysis, we have obtained a formula for controlling myopia.
二、How to build a digital sclera:
This project uses innovative scientific research system methodology to conduct innovative explorations in the field of medical scientific research. This methodology follows real-world research benchmarks, superimposes the application of digital twin technology, comprehensively applies the digital simulation capabilities of artificial intelligence in digital modeling, and transforms clinical research problems. It is a modeling and iterative evolution process that is integrated with the physical world verification.
1. Digital sclera static establishment
The second step is to use the SOLIDWORKS software to create a cross-sectional model of the 3D model based on the OCT imaging results;
In the third step, the COMSOL software is equipped with multi-physics analysis to observe the changes in scleral curvature from the upside, downside, anterior surface, equator, etc. of the sclera to obtain the entire digital sclera.
Inner shell:
On the basis of OCT software combined with B ultrasound, the parameters of each position are calculated using COMSOL software, and the software plug-in is inserted to obtain all the parameters of the inner surface of the digital sclera.
2. Digital sclera dynamic establishment process:
Using intelligent image sensors and intelligent liquid lens and image feedback software, using neural network big data computing technology, under the state of inputting multiple parameters of the eyeball, through digital processing, data fusion, all-digital transmission, and local data processing methods, the entire The cornea of the eyeball to the sclera to the lens to the vitreous to the retina, etc., combined with the fundus camera to image the fundus image on the sensor, thereby presenting the acquired high-precision picture on the display screen. The digital eyeball will automatically adjust the distance, when the center point is in focus, the image will be automatically frozen and clear. The whole dynamics is similar to the refractor and camera.
Based on the three-tuple data perspective of environmental phenotyping and biological adaptability, this project collects and simulates environmental changes, human functions, and physiological mechanisms as the main model building elements.
The simulation environment changes include the time of using the eyes at close range, the distance of using the eyes, changes in light, the amount of exercise, geographic latitude, environmental temperature, and different geographic locations may bring a variety of parameters such as temperature, light and other correlations during seasonal changes. Variety.
The simulated human body functions include: the basic perception capabilities of human binocular vision, such as the basic perception capabilities of light intensity, color recognition, pupil zoom, eye movement, and capturing of moving objects in vision;
The physiological mechanism of the simulated human body includes the size and shape of the eyeball, the curvature of the cornea, the curvature of the sclera, the curvature of the lens, the curvature of the retina, the size of the macula, the visible pathological features of the fundus, the connection with the external brain optic nerve and the ability to transmit information (visual electrophysiological examination), Special parameters such as eye axis length L, scleral hardness H, intraocular pressure P, elastic modulus E, etc.;
The establishment of the above-mentioned parameter model to the physical model, where the process from 0 to 1 is realized, we need to establish a digital twin eyeball model that can continuously iteratively evolve and integrate the original fragmentation and single perspective into digital research and development with multiple integration and global perspective. process.
三、Digital chemotherapy treatment plan for myopia prevention and control: (DTx)
We have established Digital Therapy (DTx). In the future, a large number of global medical institutions and clients will input different parameters into this software. The digital eyeball APP can continuously learn by itself. Through the artificial intelligence neural network data calculation, you can observe the eyeball from birth to old age. The entire life cycle of the app has different morphological changes. The APP is divided into customer, medical and enterprise end;
1. Client APP operation manual:
The groups are: parents, teenagers and children, who can download the Digital Eye APP by themselves, enter personal information, age, gender, close learning time, outdoor activity time, and different parameters of eyeballs, and then they can clearly observe the changes of personal digital eyeballs. Evaluate and guide the best intervention window and personalized intervention plan for myopia. The progress trend of all eye diseases such as dry eye, myopia, cataract, and glaucoma can be reflected and reflected on the digital eyeball APP. Parents clearly know the future curve of the eyeball. The client terminal will automatically record the daily sun exposure, daily learning time and various eye disease history files. The App can call the cloud service algorithm to evaluate the progress of various eye diseases and the control measures that should be taken for early warning and timely intervention. Customize individualized eye care training programs and eye care programs for individual differences.
2. Medical APP operation manual:
The hospital establishes patient data files and enters the APP, provides core data and shares data with the enterprise platform; according to the top-level scientific research tasks and multi-omics research scientific work plan constructed by the platform cooperation expert team, each medical unit is independently responsible for recruiting the corresponding myopic patients. , According to the platform algorithm and real-time feedback of digital twin model training and diagnosis and treatment plan strategies, groups to complete their respective clinical digital therapy practices.
3. Operation manual for the enterprise side (platform service):
Through the client and medical data sharing mechanism, provide the core platform with multi-omics research big data processing capabilities and assist the top expert team to complete the digital modeling and virtual simulation process of digital eyeballs, and provide the digitization of unified feature modeling for each scientific research branch Eyeball models, combined with their respective scientific research goals and plans, assist in the algorithm development and model iteration verification of various units, gather the consistency of results and benchmark differences of various scientific research branches, and continue to use the evidence-based medicine method of real-world research to improve digital therapy. Carry out optimization and perfection.
4. Combining clinical evidence-based medicine research to develop and verify digital therapy DTx
Achieve the establishment of a global multi-regional collaborative research network for children’s myopia, and conduct multi-center clinical and clinical case studies of children’s myopia. Analyze the development of children’s emmetropism and the possible risk factors in the occurrence and development of myopia, establish a dataset of children’s emmetropism, a dataset of myopic eyes, and a dataset of ocular environments, and develop a highly myopic study based on whole-genome sequencing technology. Study on the pathogenic mechanism of susceptibility genes and genetic environment interacting with each other.
The experience of AI physicians comes from the treatment process for large-scale populations. The clinical trials themselves are the verification and optimization process of the treatment plan. They are all carried out in the real world. All the experiences and plans that are conducive to the treatment of myopia are finally concentrated on In the brain of AI physicians, through continuous clinical treatment learning, AI can evaluate and customize the treatment by itself, and customize personalized digital therapy for each person through the preliminary evaluation (observing the elastic modulus).
In summary, digital therapy is:
Digital eyeball generation;
Artificial intelligence AI doctors prescribe to patients (the enterprise will prescribe it by itself based on the artificial intelligence AI data);
Private customized intervention plan
Develop a digital healing solution (DTx) for myopia prevention and control based on digital twins and AI applications:
Based on the mathematical theories, quantitative formulas, and digital twin technology models of adolescents’ myopia, a digital therapy plan for the prevention and control of adolescents’ myopia was constructed.
There are a variety of products: frame glasses; orthokeratology lens; outdoor sports; lutein; acupuncture; flipping; feeding device; linear machine, massage device, anti-blue glasses, defocus lens, contact lens, nursing eye night , Anti-fatigue eye drops, atropine, eyeglasses, eye electrotherapy device, eye patch, progressive lens, AR vision training lens, automatic flip mirror, double light mirror, double light prism, gradual additional multifocal lens, eye exercises , Ciliary muscle training device, taurine extract, multi-functional training device, neuro-visual enhancement system Gabor vision target, distant view method, blinking method, etc.
In addition, we have added the following three new methods;
1. Eye drops that increase the elastic modulus of sclera:
Contains Hydroxyproline (HYP), which has the effect of increasing the diameter of scleral collagen fibers and increasing the diameter of scleral fibers, thereby reducing the development of myopia.
Instructions:
Use the artificial intelligence big data computing system to calculate the best intervention window for the scleral elastic modulus, calculate the required concentration of HYP, determine the amount of collagen in the scleral tissue, instill the corresponding eye drops, and calculate the use period. Has reached the effect of increasing the elastic modulus of the sclera, thereby preventing the development of myopia. This method is a multi-level study of the development and regulation mechanism of children with high myopia in molecular biology and organization. Use digital eyeballs to verify the effects of the whole life cycle.
2. Scleral elastic modulus measuring instrument: A measuring device and method for scleral force and stress, which can measure the change in scleral hardness and the optimal threshold window for scleral intervention.
Instructions:
A device and method for measuring the value of scleral force and stress is used. A 3KHZ ultrasound probe is used to transmit ultrasound on one side of the sclera and receive the transverse transfer stress wave of the transmitted wave on the other side.
The transmission control module is used to control the ultrasound probe to emit ultrasound to the sclera and receive the echo of the ultrasound to obtain the first echo data; after the first echo data is obtained, the ultrasound probe is controlled to generate a Lamb wave in the sclera; the ultrasound probe is controlled again Transmit ultrasound to the sclera to detect the lamb wave passing through the sclera, and receive the echo of the ultrasound to obtain the second echo data; the data processing module, the display module is used to calculate the scleral shear stress value, and the lamb The high reduction coefficient of each displacement of the wave, and the scleral elastic modulus value is calculated accordingly.
The elastic modulus measuring instrument is used to detect the different elastic modulus parameters of the sclera, such as the anterior surface, the equatorial part, and the posterior part.
3. Octopus robot: Change the curvature of the sclera, treat myopia, and control the myopia rate above 90%.
This technology can subvert medicine in the field of myopia prevention and control.
Instructions:
The transformation of pseudomyopia into true myopia is the time window for our intervention. The target of intervention is the curvature of the sclera. Once the curvature of the sclera changes, the eye axis will continue to grow irreversibly.
The octopus robot uses the micro-negative pressure system to interfere with the scleral curvature to change the ratio of the Y-axis and X-axis of the eyeball, so as to control the growth of the eye axis and reduce the refractive power. Just like orthodontics for children.
Through the above products, the goal of preventing, controlling and curing myopia can be achieved, and the global rate of myopia can be controlled and cured to more than 90%.
A large number of digital therapy programs combined with a large number of products are as high as 100 to the 100th power, which cannot be calculated by manpower. AI doctors have the ability to screen and verify massive large-scale data, and finally find the best combination of personalized solutions.
四、Real-world research and clinical verification (RWS) of the digital therapy for myopia healing DTx:
Multi-center digital therapy clinical verification reference evaluation indicators:
Based on a large population cohort, carry out clinical efficacy verification: establish an open data set, DigitalEyes_DataMart (Global Open Digital Eyeball Data Mart), develop a process from 1 to 100 based on the digital twin eyeball model, high-quality data range and sample distribution, and The evolution of the algorithmic probability model determines the evolution and development of AI physicians’ group learning intelligence in this project. Through group confrontation, reinforcement learning, neural network, parameter system model automation (adjusting parameters), data feeding (data identification), physical model (digital human body/eyeball) and other technical applications, we will comprehensively transform to the development of digital clinical diagnosis and treatment programs.
1、Establish an open data mart:
In order to promote the generation and evolution of the twin model of digital eyeballs, the collection and aggregation analysis of multi-omics and multi-modal data of large-scale population cohorts are required, and the target task research and data iteration verification in the field of large-scale crowd cohorts and multi-omics can be carried out. In the original digital eyeball twin model, a series of artificial intelligence data processing basic technologies, such as data cleaning, data labeling, data training, and data feeding, are used to construct a large-scale independent and identically distributed fusion data training set as the digital processing base model of the digital eyeball ( Digital Fundamental Base). We initiated the establishment of the global open digital eyeball data mart OpenDigitalEyes_DataMart (ODEDM, the global digital eyeball open data mart);
Invite world-renowned hospitals and top ophthalmologist teams to join the collaborative team to realize the establishment of a global multi-regional collaborative research network for children’s myopia; carry out multi-center clinical myopia etiology and pathology and digital therapy (DTx, Digital Therapeutics) research in children’s myopia;
Analyze the development of emmetropism in children’s eyes, and the risk factors that may exist in the occurrence and development of myopia;
Establish children’s emmetropization process data set, myopia eye data set and eye environment data set;
Carry out research on the pathogenic mechanism of the interaction between high myopia susceptibility genes and genetic environment based on whole-genome sequencing technology.
2. Establish a global opener community
Based on the above-mentioned Internet clinical medicine multi-center and global research and developer collaboration network, we initiated the establishment of an open source community OpenDigitalEyes_DevCommnity (ODEDC, Global Digital Eyeball Developer Community),
Further through cooperation with large-scale ophthalmology institutions around the world, the goal is to predict that 100,000 people will be enrolled in the group to track the evolution of eyeball development over a period of 10 years.
Establish a full-featured digital twin model of eyeballs for 100,000 people, and dynamically fit the change curve of eyeball development and growth characteristics according to the development and changes of their eyeballs in the past 10 years.
Therefore, based on the unified consensus base and the distribution of different characteristics, technologies such as group confrontation, reinforcement learning, neural networks, and parameter system model automation (parameter tuning) are used to empower the realization of specialized individual digital twin eyeball models (digital individual eyeballs) .
From generic simulation to feature fitting, this project fully follows the guiding principles of real-world evidence-based medicine research, and realizes the twin modeling process of digital individual characteristics based on clinical collaboration, thus perfecting the evolution and development process of digital eyeball prototypes from 1 to 100.
Consensus based on commonality builds basic functions and rules for digital eyeballs. Data sets and rule sets based on retaining individualized and specialized differences reflect the characteristic distribution of individual individuals, and the homomorphic multi-distribution probability model of large-scale population data The data range and sample distribution have formed and discovered the biological adaptability and diversity development law of the digital eyeball evolution,
Through experiments, the AI intelligent evaluation and diagnosis and treatment decision-making model constructed by the digital eyeball as the frame of reference is also completed, and the personalized digital healing plan DTx is further developed.
Reference evaluation index for clinical verification of multi-center digital therapy:
Scleral elastic modulus measuring instrument: a measuring device and method for scleral shear stress value (medical technology evaluation standard), the evaluation index is: individual elastic modulus E under age, region, genetic factors, living habits, environmental conditions The change trend and distribution characteristics of myopia, and compare with the standard measurement of myopia and calibrate the measurement deviation;
Eye drops that can increase the elastic modulus of sclera: Calculate the concentration of HYP needed to determine the amount of collagen in the scleral tissue (chemical intervention digital therapy), the evaluation index is: by measuring the scleral hardness (elastic modulus E) and targeting the test The patient was given a dose-climbing experiment with different HYP concentration ratios within a safe range to evaluate the diagnosis and treatment effects and adverse reactions of the treatment method under age, region, genetic factors, living habits, and environmental conditions, and compare it with other treatment strategies. A comparative analysis of the curative effect of the treatment plan and the length of treatment used.
Octopus robot: change the curvature of the sclera (physical intervention digital therapy), the evaluation index is: by changing the curvature of the sclera (indirectly affects the elastic modulus E), and give the subjects different scleral curvature changes within a safe range Evaluate the diagnosis and treatment effect and adverse reactions of the diagnosis and treatment method under the differences of age, region, genetic factors, living habits, and environmental conditions, and compare and analyze the curative effect of the group treatment plan and the treatment time used with other treatment strategies.
Summarize:
As human beings continue to evolve, life expectancy is getting longer and longer, from 0-50 years old to 0-100 years old now. The ability to adapt to society has also changed from physical labor to mental labor, and the eye environment has also changed (learning Factors such as behavior and electronic products), from the original behavior of looking far away to the current behavior of using eyes at close range for a long time. But the eyeball has not evolved. Through the digital twin eyeball software, we found that the original eyeball could not adapt to the current social environment, leading to more and more eye diseases such as myopia, cataracts, glaucoma, and so on. At the same time, the scleral elastic modulus energy content of the eyeball is insufficient, and the myopia rate continues to rise, so we need to change the elastic modulus of the sclera to adapt the eyeball to the current social environment.
Through digital therapy DTx, find relevant markers and target points, so that everyone can see their eyeballs at a glance, clear and intuitive; integrate multi-center myopia-related factors big data, through multi-modal and multi-dimensional deep learning prevention and comprehensive analysis, Extract the environmental and genetic risk factors that may lead to the development of myopia and high myopia, and construct a predictive model that takes into account the prediction and clinical interpretability of adolescent myopia assessment and refractive changes; the biggest advantage is convenience and safety, allowing patients to reduce psychological pressure and healing It is painful, and greatly reduces clinical costs, realizes global multi-center collaboration, speeds up the acquisition of the best solution for myopia control, greatly improves efficiency, and achieves a reduction in the global myopia rate.
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