Development of myopia.
There has been an ongoing debate about the causes of myopia occurrence and development, and related myopia control and treatment products are making their way under the brand name of various theories. For myopic patients, the unchanging life brought by myopia is a very painful affair. And for parents of myopic children, their children’s glasses have undoubtedly become a piece of mind for parents. Therefore, the causes of myopia and how myopia develops has become a common concern for many experts, scholars, parents and all myopia sufferers.
Overview.
Genetic factors, regulation theory, blur theory, and biochemical indicators are considered to be several causes of myopia formation. The national discussion on the formation of myopia generally considers regulation to be an important cause of myopia onset and progression. The main basis of the regulation theory is the action of intraocular muscles caused by regulation, the action of extraocular muscles caused by trigeminal action, and the change of intraocular pressure caused by vergence and regulation. So what are the main causes of myopia? Are some of the bases mentioned above wrong? In this paper, we will elaborate on these questions and present our views and opinions based on some available information.
I. Two major theories of myopia formation.
(i) Regulation theory.
The regulation theory is the oldest theory in the study of myopia etiology and is still respected by many scholars. It is believed that when working at close range, the regulation and assembly are the intraocular and extraocular muscles acting on the sclera, and that the sustained high intraocular pressure is responsible for the growth of the eye axis, leading to axial myopia.
1, the role of the intraocular muscles: when using the eyes for a long time at close range, in order to bright vision objects, the regulation is constantly strengthened, the ciliary muscle continues to contract, causing tension and spasm and induce myopia. Due to the resistance of the ciliary muscle pressure, and the choroid that is excessively stretched cannot be restored to its original state, the blood volume continues to decrease, gradually losing its elasticity and buffering capacity, followed by malnutrition and atrophy. The lack of elasticity of the sclera also begins to deform, resulting in the lengthening of the posterior pole and the formation of myopia.
2, the role of extraocular muscles: symmetrically attached to the surface of the eye four pairs of straight muscles (internal rectus, external rectus, superior rectus, inferior rectus), not only to maintain a variety of forms of eye movement, but also the mechanical traction on the eye to produce pressure, when the convergence of the eyes, the contraction of the internal rectus muscle pressure, resulting in an increase in the anterior and posterior diameter of the eye, leading to myopia.
(ii) There are several problems in the theory of accommodation.
1. We know that the lens is in the anterior 1/3 of the eye, while the suspensory ligament and ciliary muscle only cause traction on the sclera in the anterior 1/3 of the eye. In addition, the intraocular pressure is regulated by the atrial fluid, which is in front of the lens, i.e., before the anterior 1/3 of the eye, and when the intraocular pressure rises it is a pressure on the entire inner wall of the eye and does not affect only the posterior pole of the eye.
As you know, the process of myopia development is actually a process of eye development, in which the entire eye gradually grows from small to large, and the entire inner chamber of the eye also becomes larger at the same time. The choroid is sandwiched between the retina and the sclera. What will happen if the choroid atrophies while the eyeball continues to grow?
3, we know that the movement of the eye is not done with all the muscles contracting at the same time, but some muscles contract while others are in a relaxed state, when the eye is subjected to a force along a certain line of the eye, making the eye turn. For example, during the collection movement, the inner rectus muscle contracts and the outer rectus muscle relaxes, causing the wall of the eye on the nasal side of the eye to be pulled inward along the tangential direction, causing the eye to turn inward. Instead of contracting both muscles at the same time, if the eye is contracted at the same time the eye is pulled in the opposite direction and the eye cannot turn, this pull only causes a pull along the tangential direction of the eye, not a pressure on the eye. Even if pressure is caused, it will be due to this pressure that limits the growth of the eye and cannot lead to a longer eye axis. We know that the eye has its own function of controlling internal pressure, atrial fluid is produced with the ciliary process and excluded by the trabecular meshwork. When the intraocular pressure rises to a certain level, the discharge of atrial fluid will be accelerated in order to maintain the stability of intraocular pressure, otherwise it would not become glaucoma. The internal pressure control mechanism of the eye is like a car brake cylinder, if the air is only in and out, then eventually the cylinder will explode due to high air pressure, in order to solve such problems, the cylinder is installed on a pressure regulating exhaust valve, when the internal pressure of the cylinder reaches a certain level the valve will open to discharge a certain two air and then close to ensure that the internal working pressure of the cylinder normal. The same eye also has an internal pressure regulation mechanism. In fact, external pressure does not necessarily cause an increase in IOP. For example, before doing glaucoma surgery, sometimes the method of pressure on the eye is used to lower the intraocular pressure, this method is to force the atrial fluid to be removed by applying pressure on the eye.
4. The traction of the intraocular muscles and the pull of the extraocular muscles on the eye should be a pair of opposing forces. The intraocular muscles cause the regulation of the crystal to cause inward traction on the sclera, while the extraocular muscles cause the rotation of the eye by causing outward pull on the outer wall of the eye. Aren’t these two forces opposed to each other? So how do these two forces act on the eyeball to make it grow? And which force plays the key role?
(iii) Fuzzy theory.
The blur theory suggests that poor retinal imaging quality is an important cause of the onset and progression of myopia. Refractive errors are the main cause of blurring. Severe blurring then causes form deprivation. When all distances are produced form deprivation will eventually result in amblyopia. Otherwise, it can promote the growth of the eye and increase the risk of myopia or lead to rapid progression of myopia. That is, form deprivation and blurring can result in two different outcomes.
There are two causes of blurring.
1. An out-of-focus optical image caused by an abnormal refractive state, resulting in blurring. At this point both central vision and visual field are in a blurred state.
2, although the adjustment makes the near-center vision clear, but the field of vision is in a blurred state, and the stronger the adjustment the more blurred the field of vision. We just look at a book of 40cm, at this time we can easily find that the words on the book is clear, but the other images on the field of vision outside the book are blurred.
It is easy to see that there are some contradictory theories of regulation-induced myopia. There are also a variety of products derived from these theories, so how effective are these products? From the myopia control tablets we can see the fact that with the use of myopia control tablets, it does not play a good myopia control effect, so why is this? The myopic control piece is based on the regulation theory. The blurring theory applies not only to out-of-focus and form deprivation, but also to the state of accommodation so how should the causes of myopia be reasonably explained? Let’s take a look at two related experiments.
II. Relevant experiments.
1, in the famous rhesus monkey experiment, in a bright environment, by blinking lid suture, so that the retina imaging blurred, and the optic nerve at the optic cross cut, after a period of feeding, the results of the rhesus monkey or the formation of miles myopia. After the optic nerve was severed, regulation, assembly, and even normal visual function were lost.
In 980, Wallman et al. made experimental comparative observations on Rhesus monkeys based on the fact that the eyes of chickens have two functions: to look far and to look near. group A covered both eyes to the side (division of far) and could only look to the front room of the tip of the mouth (division of near); group B covered the forward vision only to look far; group C covered the right eye with a translucent membrane in front of the eye. Refractive examinations and measurement of the axial length of the eye were performed from 4 to 7 weeks of feeding. The results obtained were that the refractive power of the chicks in group A was similar to that of the chicks with normal eyes, and group B showed high myopia (mean 10.00D), and accordingly the axes of the eyes in this group grew significantly compared to group A. Group C, with the transparent film covering the eyes, also showed high myopia (mean -12.00D), and the degree of myopia was greater than in group B. What problems can we see in the chick experiment?
In fact, the rhesus monkey experiment and group C of the chick experiment reduced the clarity of imaging and caused blurring of the retinal image, thus confirming that blurring is another key cause of myopia. Group B of the chick experiment, on the other hand, seems to confirm that accommodation does play an important role in the development of myopia. So doesn’t this just prove that the regulation theory is also correct? To answer this question let’s take another look at some of the biochemical indicators of alterations that affect eye development.
Third, Raviola and Wiesel have reviewed the following results.
1. If monocular eyelid sutures are placed in a dark room, the result is the same refraction in both eyes and the same length of the eye axis. If later reformulated in a normal environment, a lengthening of the sutured eye axis was seen, resulting in a 3.0D myopia while the other eye remained 2.0D hyperopic. It shows that mechanical and temperature factors do not induce excessive growth of the eye axis, but the key role is abnormal visual afferent stimulation.
2. It is believed that causing corneal clouding to abnormal afferent visual stimuli lengthened the eye axis by 1.0 to 1.22 mm after 1 year compared to the control group, corresponding to 4.0 to 6.0 D of myopia. This is different from the results of eyelids placed in a dark room despite suturing, indicating that the nervous system plays a definite role in the development of myopia.
3. To understand the possible role of regulation in the formation of eyelid suture myopia, four tree-tailed monkeys were given daily eye dots of atropine, and no increase in the eye axis was seen after 1 year, but the results were different in three rhesus monkeys.
Possible causes.
(i) Atropine does not work in rhesus monkeys.
(ii) The experimental myopia induced by the two animals has different neural mechanisms.
③There is a difference in the response of the two monkeys to atropine blockade of cholinergic M1 receptors on the retina.
(4) The experimental eyes with removal of the ciliary ganglion and disruption of the parasympathetic innervation of the ciliary muscle produced myopia larger than 10.0 D in the other eye 1 year after lid suturing, and the vitreous cavity was also enlarged by 2.0 mm. This demonstrates that regulation does not play a role in the formation of myopia and supports the theory that there may be two different mechanisms, i.e., regulation may be involved in the formation of myopia in one group of animals, which may be related to the blurring of the visual field caused by regulation resulting in biochemical This may be related to the alteration of biochemical parameters due to regulation-induced visual field blurring. In the other group of animals, regulation does not play a role, but is determined by the mechanism of the retina itself.
In order to demonstrate the role of the sympathetic nervous system, i.e., the sensory nerve, in lid suture-induced myopia, the superior junctional ganglion and the trigeminal nerve were removed and neither was found to have a role in preventing the lengthening of the eye axis.
6. In some animals (rhesus monkeys), because of the retinal mechanism of action, afferent nerve stimulation is only localized (by cutting the optic nerve at the optic nerve crossing) and can also induce myopia (4.0-9.0 D).
IV. Biochemical alterations and eye development.
In recent years, biochemical studies related to myopia have shown that the occurrence of myopia is related to changes in the biochemical substances of the retina, of which the more studied are retinal neuromediators and retinal growth factors. The former includes retinaldehyde, dopamine, and acetylcholine, while the latter includes transforming growth and basic fibroblast growth factor beta.
Retinoic acid (RA), the active metabolite of vitamin A, binds to nuclear receptors of transcription factors and regulates cell differentiation for growth. Experiments have shown that altered metabolic processes of RA have an important role in the development and progression of experimental myopia. In an animal model of optical defocus, -15D spherical lenses caused an increase in retinal retinoid content and a decrease in choroidal retinoid content; conversely, +15D spherical lenses caused an increase in choroidal retinoid content and a decrease in retinal retinoid content; exogenous retinoids caused a 100-fold increase in endogenous retinoid content in the retina, and eye length was considerably greater than that of control group. Thus, it was hypothesized that retinal retinoids reduced the synthesis and release of choroidal retinoids, causing an increase in scleral proteoglycan synthesis, which ultimately led to changes in eye axis length.
Dopamine (DA) is an advance in the synthesis of epinephrine and norepinephrine in vivo and is one of the major neuroactive substances in the vertebrate retina. The determination of DA content in the serum of secondary school students showed that the serum dopamine content was significantly lower than that of normal controls in both mild and moderate myopia (P < 0.01), while there was no significant correlation between DA content and gender and degree of myopia in the myopic group (P > 0.05). Animal experiments demonstrated that the DA agonist apomorphine significantly inhibited the excessive prolongation of the eye axis in form-deprived eyes in a dose-dependent manner. In contrast, the DA receptor antagonist fluorocarbophil counteracted the secondary effect. Thus, it is hypothesized that DA is involved in the complex regulation of the visual nerve on the axial growth of the eye. This idea was further confirmed by the experiments of Shaoshan Guo, who sutured one eyelid of a chicken with a highly myopic eye with a prolonged eye axis for 2 to 4 weeks. Examination revealed that the dopamine content in the retina was 40% lower than in the unsutured eye, confirming the role of dopamine in myopic eye formation (and that this process is reversible), and that the growth of the eye was inhibited after subconjunctival administration of apomorphine to the chickens.
Acetylcholine is also a neurotransmitter involved in myopia formation. The composition and distribution of the cholinergic transmitter system is very complex, and its receptors can be divided into M receptors and N receptors. In experiments, vitreous cavity injections of the nonspecific cholinergic blocker atropine and the specific cholinergic M1 receptor blocker Pirenzepine attenuated the growth of the ocular axis in an animal model of formant deprivation, whereas injections of the specific cholinergic M2 receptor blocker Methoctramine and M3 receptor blocker 4DAMP had no effect on the growth of the ocular axis. The same results were obtained with ocular surface use of Pirenzepine. It is therefore hypothesized that the regulation of the ocular axis by cholinergic substances is achieved through M1 receptors. Since M1 receptors are not present in the iris and ciliary muscle of the human eye, the modulatory effect of atropine on the growth of the ocular axis is not related to regulation, but occurs by blocking cholinergic M1 receptors in the retina. However, for ocular growth in high myopia, M cholinergic neurons are not necessary. Instead, it is most likely related to N cholinergic mechanisms. Experimentally, it was demonstrated that both the relatively non-specific N receptor antagonists, sondalonium chloride and mecamylamine hydrochloride, inhibited the formation of high myopia in a complex dose-related manner.
Transforming growth factor (TGF-β) is a factor that can inhibit or stimulate the growth of different cells under different conditions. urokinase fibrinogen activator (uPA) or tissue fibrinogen activator (tPA) can participate in the activation of TGF-β by increasing the concentration of fibrinolytic enzymes, and fibrinogen activator (PAI- I) may be involved in the mechanism of retinal regulation of scleral growth.
Basic fibroblast growth factor β (bFGF) may be one of the important factors in the retinal regulation of the ocular growth pathway, and its expression level is regulated by information. bFGF effectively antagonizes the formation of high myopia. It has been observed that blurred images can alter the indicators of bFGF, and intraocular injection of bFGF can effectively prevent high myopia formation and eye axis lengthening. The reason may be that blurring reduces the synthesis or release of bFGF by the retina, or the number or sensitivity of nFGF high-affinity receptors.
V. Speculations about myopia formation.
Is the key to eye development the result of external forces or is it due to blurring? Or is it controlled by biochemical indicators? What factors are associated with the alteration of biochemical indicators?
Simply put, the development of the human body must be related to a variety of biochemical indicators, and the eye is no exception. Then, changes in biochemical indicators related to eye development must be related to individual differences, genetics and different physiological ages, in addition to certain other factors that can also affect these biochemical indicators. In addition, certain other factors may also influence these biochemical parameters, such as body composition, diet, eye habits, etc. We will mainly consider here the relationship between eye use and myopia. Why does myopia occur at a higher rate due to the increased burden of study? How is this related to close eye use? Is the basis of the traditional regulation theory correct? To understand this question, we need to analyze the two previous experiments.
The rhesus monkey experiment illustrates that there is no direct relationship between accommodation, pooling, and the development of myopia, and the conclusions of Raviola and Wiesel confirm that mechanical external forces caused by accommodation are not a factor in the overdevelopment of the eye. In contrast, the experiments demonstrated that reduced image quality nevertheless leads to the onset and development of myopia. This conclusion is supported by the results of chick experiment C. But what does the chick experiment group B tell us? Many people think it just proves that accommodation plays an important role in the onset and development of myopia. However, isn’t it as simple as that? The chick in group B was restricted from looking far away and only allowed to look close. First of all, I need to think about how much time the chick spends looking at the near, and whether he keeps looking at the near as soon as he opens his eyes. Obviously such an answer is not logical. If not, then is the distant form of perception limited when it is not looking close? Even if the chick is constantly looking close, we know from the previous blur theory that the visual field is always blurred when near-use conditioning is generated, and the stronger the conditioning the more blurred the visual field. Therefore, the results of this group do not effectively show that there is a direct relationship between regulation and myopia, but rather better evidence that the blurred visual field caused by regulation is an important cause of myopia.
Based on the above, we can speculate that. First, the development of the eye is regulated by a variety of biochemical indicators. These indicators are influenced by various internal and external factors, such as individual differences, genetics, and different biological ages, as well as external factors such as body composition, dietary structure, and eye habits. Further research is needed on how internal factors affect biochemical indicators to regulate the growth and development of the eye, but current research has shown that the growth and development of the eye can be controlled by altering biochemical indicators, laying the foundation for future research on drug therapy for myopia. How do external factors affect myopia?
We can conclude from the appeal experiment and various bases that the blurring causes the biochemical index changes to cause the overdevelopment of the eye, not the action of the intraocular and extraocular muscles in the regulation theory. However, it is undeniable that the changes in visual field imaging clarity caused by accommodation are indeed involved in the alteration of biochemical indicators. This explains why the percentage of myopia increases as students spend more time with their eyes, and why the means to control the onset and progression of myopia by reducing accommodation, based on the accommodation theory (action of intraocular and extraocular muscles), are ineffective. This is because regulation affects the growth and development of the eye through changes in biochemical indicators caused by blurring of the visual field. Or in general, blurring is an important cause of myopia.
VI. How to properly control the development of myopia.
Trying to effectively control the development of myopia is still a very difficult problem at the moment. In order to control the development of myopia well, it is necessary to address the internal and external factors that cause changes in the biochemical indicators of eye development, and only in this way can the occurrence and development of myopia be effectively controlled. However, it is still quite difficult to solve the internal factors, so it is still impossible to eradicate myopia completely. But are we able to exert some control through external causes? Since we know that blurring is an important cause of the occurrence and development of myopia, then as long as we address the problem of blurring, the quality of imaging problems can get good results. The solution is myopia foot correction, which goes against the traditional principles of myopia giving light, but it is indeed the best and most effective means of myopia control. However, there is no good solution for the blurred vision caused by accommodation. The reason is that either the use of accommodation or the use of optical methods to reduce accommodation can cause blurred vision. Therefore, in developing adolescents and children, controlling the amount of time spent in close proximity is the best method of myopia control. In addition, physical and dietary structure can also have an impact on the onset and progression of myopia. A proper diet and good physical condition are also effective tools to combat the onset and progression of myopia. However, when some people hear about nutrition, they think that the more nutrition the better, but in fact, balanced nutrition is the only way to ensure the normal development of the body and the eye.
The conclusion is that the causes of myopia formation and development are not the result of a single factor, but the result of a combination of factors. Only when the causes of myopia are accurately understood, we can take effective measures to control the formation and development of myopia. In the current situation, it is impossible to eradicate myopia, but through the regulation of external factors, it may have some effect on the control of myopia. The actual effectiveness of current myopia control products is a debatable issue.