Myopia and its vision threatening complications present a significant public healt problem.The review aim to provide an update overview of the multitude of know to control the prevalence and the progression of myopia. Role of ortokeratology lenses and multifocal lenses, optical interventions and application of atropine are not invesigated as beyond our aims. A systematic literature search was conducted on relationship between the myopia and its enviromental influences on eye growth.

• Children; Myopia;Visual Environmental Factors; Role of Genes; Near-Work; Outdoor activity

Sorcinelli R (2024) The Shift Of Myopia Progression: A Mini-Review. JSM Ophthalmol 11(1): 1094.

Refractive errors are the consequence of a mismatch between the axial length of the eye and its dioptric power which ultimately leads to the result of indistinct vision. Myopia is a refractive error produced by an excessive length of the eye compared to its dioptric power. This is owing recent rise in its prevalence worldwide. The growth is increasing significant in East Asia where in some areas, for example Taiwan, it has reached an incidence of 84% of the population over 18 years of age [1]. By 2050 it is projected to affect more than 50% of the world’s population [2]. The increase is so rapid as to suggest that myopia is a complex condition, influenced by numerous factors,including genetic predisposition, environmental influences and certain lifestyles. Both environmental influences and individual behavioral factors play a crucial role in the spread of myopia, modulating the expressivity of genetic factors on the growth of the eye. Expressivity is given by the extent to which a gene is expressed and can be indicated with a percentage, for example 50%, when only half of the characteristics could occur in individual phenotypic. Emmetropization is another key concept underlying the change in refraction over the course of age: this occurs during the neonatal period and is linked to the normal growth of the eye after birth. The length of the eye at birth is approximately 18 mm and at 3 years approximately 22-23 mm. Consequently the refractive error decreases during this period until at 5 years, when for most part children are functionally emmetropic. Studies on animal models ,such as the monkey, have shown that the peripheral retina can exert one’s myopogenic stimulus that lead to growth in axial length and therefore can participate in the emmetropization process. The mechanism that regulates the growth of the eye iis linked to a feedback control guided by vision. This feedback mechanism would be the basis of the growth of axial length when forms of visual deprivation occur, as happens for example in extreme cases of congenital cataracts or total eyelid ptosis or in the case of the insertion of focusing lenses [3]. We can hypothesize that also in normal emmetropization the feedback mechanism is always the same and starts from the retina which controls and decodes the errors induced by defocusing. With increasing age, i.e. towards 6-8 years, myopia might appear followed by a slow stabilization process between 15-21 years of age [4]. After a period of apparent stabilization, however, the eye remains susceptible to environmental influences. This typically occurs tipycally in university students or even later in life where there is a progression or development of myopia [5].

Variations in Myopia Dependent on Age and Ethnicity

The incidence of myopia has rapidly increased in recent decades throughout the world. In a recent meta-analysis of studies on the world population. Pan et al. [6], reported a percentage of myopes of 47% in the age group between 20-29 years, compared to 26% in the age group between 50-59 years. The RESC study (Refractive Error Study in Children), involved 8 of the most disparate locations in the world (from Nepal to India, China etc.) but using standardized samples. The results showed that in in 15-year-old children the incidence of myopia was 0.79% in the rural areas of Nepal, climbing to 4.29% in the urban areas of New Delhi, to 48.7% in the rural areas of China and to 79.9% in urban China. Therefore a wide variability linked not only to ethnicity but also to local regional differences, urban areas vs rural areas [7,8]. Therefore there is evidence of strong environmental influence over refractive development. We have already descrbed animal models where errors of refraction are experimentally induced by the suturing of the eyelids or by opaque occluders which induce an elongation of the eye in monkeys.The same situation may to repeate in children in whom there has been visual deprivation during the period of ocular development. But wich is the basis of the feedback mechanism guided by vision and modulating the growth of the eye?. The key to everything may be the sclera. The sclera is a rigid cartilaginous-like connective tissue made up of an extracellular matrix (ECM) produced by fibroblasts. Environmental exposures trigger a cascade of signals (evoked by vision), that originates in the retina, passes through the choroid and initiates a remodeling of the sclera which is activated with the production of the extracellular matrix (ECM)[9]. Many genes are involved in the growth of connective tissue and of the extracellular matrix and may undergo variations in their effects on refraction as a result of their interactions. To better define the influences of the environment on the progression of myopia in teenagers we recall the work of Zylbermann et al. [10], in this renard, always cited as emblematic, in which 870 male and female adolescents of the Jewish race were monitored.Was esamined a group of 193 males who attended Orthodox Schools whose programs included a very rigorous study of religious texts. The other group of boys attended general schools without religious studies. The first group had an average refractive error of -2, 9 D, the other group -0.9 D. The Authors emphasized that the difference was due to the intense and prolonged study of the religious texts of the first group of males. No difference of refractive error was found between girls who attended general schools and those of Orthodox Schools as the study continued and estended was not requested how in the males.

Role of Genetics

It is commonly found that children with both myopic parents have a greater risk of becoming myopic than those with only one myopic parent. To study the genetic role in the development of myopia, various approaches have been used which we summarize:

1) Homozygotic twins are very suitable for the study of genetic aspects that can be modified in different environments because they have 100% of their DNA in common and therefore represent an effective tool for understanding how much is inherited and how much is not inherited because it is due to the environment

2) The GWAS (genome-wide-association-study). The study of the human map of the human genome has led to the discovery of 30 distinct loci for myopia and 25 genes involved in ocular refraction whose variants are the most common forms of genetic variation in human DNA linked to the alteration of the genetic code generally due to the “building block” (nucleotide). Genes can interact with each other (gene-gene interaction) or interact with exogenous environmental factors (gene-environment interaction) modulating the eye growth.

3) Epigenetics. We speak of epigenetics when the phenotype (characterised by certain characters) no longer corresponds to the genotype or the alterations in the phenotype are linked to changes in the expressional power of the gene, due to environmental factors rather than to the DNA sequence and the genetic code. This last mechanism, which has a crucial role in the growth of the eye, is the one that is receiving the most attention from researchers

Risk Factors Related to the Environment

The role of the so-called “near work” in the development and/ or progression of myopia still remains undefined, given the wide variety of situations such as reading, type of characters, reading time, interruptions, electronic devices, cell phones, smartphones, play stations etc. These varietys have created a series of discrepancies in the study method which have led to inconsistent results: certainly the use of electronic devices has been increasing in recent decades in step with increase in myopia even if it has not so far been possible to establish and quantify the direct link with the growth of the bulb. The theory of hypo-accommodation or fluctuation of accommodation or “accommodative lag” could explain how the images of a object placed at close range focused behind the retina creates the so-called “hyperopic defocus”, constituting a risk of increasing the length of the bulb and therefore a risk of myopia. High values of “accommodative lag” would be considered dangerous for the development of myopia because the hyperopic defocus (focus plane behind the retina) triggers an “increase” signal of elongation of the eye, while myopic defocus (focus plane in front of the retina) triggers a “stop” signal [11]. To date, however, three large-scale studies have been carried out in humans [12-14], without consistent evidence of a link between hypoaccommodation and progression of myopia. Therefore at the moment the role of the increase in hyperopic defocus as a risk factor is still controversial. Since hyperopic retinal defocus is found above all in limited environments and even more so in reading that takes place at close range, eliminating near work and consequently hyperopic defocus on the peripheral retina theoretically the risk of development and/or progression of myopia should be reduced.

Activities in Open Environments and Prevention of Myopia

While reading or working closely could increase the risk of myopia, other environmental factors that are no longer “indoor” but “outdoor”, such as participation in sports or even spending time outdoors have been associated with a reduced risk of myopia.Trials conducted by 3 chinese scholars [15-17], have highlighted a reduction in the incidence of myopia of 5-10% in children aged 6-14 years but no effect on the progression of myopia i.e. no effect on already myopic children. Among other things, this lower incidence would be limited to children with a strong family predisposition, i.e. children with two myopic parents compared to children with no myopic parents. In a more recent study conducted in China [18], on a total of 1903 children in an intervention group were introduced to a mandatory 40-minute outdoor lesson a day. After a three-year follow-up in the intervention group the incidence of myopia was significantly lower than in the control group (30.4% vs. 39%) and the change in refractive error was slightly lower (-1.42 diopters vs. -1.59 diopters). The underlying reasons why the increased time spent at apert is linked to lower incidence have not been clarified, but it was hypothesized on evidence from animals that intense light produced a greater release of dopamine from the retina which in turn slowed down the axial elongation of the eye. In the wake of this work others have been done, for example in Taiwan they have introduced an educational policy with a minimum of 80 minutes a day in the open air with a reduction in the incidence of myopia from 17% to 8%. In Shanghai they have reached a maximum daily time of 120-150 minutes studying the cumulative external light intensity. The benefits persisted at 2 and 3 years. The results are a decrease of 0.5mm in axial length, a myopic shift of 1.2 diopters and an 11.7% incidence [19]. It is expected that as the incidence of myopia decreases, the incidence of high myopia will also decrease. The biological mechanism of this inverse relationship between outdoor activities and the development of myopia has not been clarified. Studies carried out on primates have established that high levels of light can delay the development of myopia: the protective effects of outdoor activities would be due to higher levels of light in outdoor environments than indoors. However, differences in study methods regarding the brightness and composition of the light used make it difficult to specify its role and remain unanswered questions. As regards the possibility that sport can affect the trend of myopia, it has been established that participation in indoor sports is not linked to a reduced probability of developing myopia [19], so studies carried out on outdoor sporting activity seem more linked to the duration of time spent outdoors than to participation in athletic activities. Other strategies to prevent myopia are currently being studied and concern the use of red light (650nm wavelength). Animal studies have explored the influence of lighting wavelenght on eye growth:the responses in diurnal red (long wavelength) to monochromatic rearing conditions in chicks, guinea pigs and monkeys are not univocal. Nevertheless variations of direction of axial lenght of the eye in the responses to monochromatic rearing conditions across species suggest that the retina may use chromatic aberration to decode defocused images [20]. In children red lighting (long wavelenght) induces hyperopia .Using red light (with a wavelenght of 650 nm) trough a desktop light therapy device at home has recently demonstrated that during a followup at 12 months,the group of 246 children receiving red light treatment exhibited a remarkable decline in myopia progression [21].The difference in axial elongation were 0,26 mm and -0,59 D in spherical equivalent refraction (SER) between RLRL (repeated low-level red light), and control group. The autors concluded that repeated low level red-light is promising alternative tratment for myopia control in children with non documented functional or structural damage. However further investigatios are necessary to comprend the mechanisme of protective effect of lighting wavelenght in children. Outdoor light and perpheral defocus could act against the onset of myopia with Dopamine secretion. Intensified illumination could increase dopamine secretion from retina and slow down the axial elongation process. Several reviews reported that retinal dopamine is typically higher during the day and may play a role in eye lenght in entraining the intrinsic retinal rhythm to the light-dark cycle, where dopamine levels are typically higher during the day. Retinal ganglion cells may provide inputs to this dopaminergic pathway. Further study are necessary to evaluate dopamine turnover in vivo and state the role of retinal dopamine in the protective effect of outdoors against myopia in humans [22]. Inconsistence is the role of dietary factor  as risk factor for myopia: children with myopia must prevent excessive body weight. It seems that children with myopia have a lower intake of fat, omega3 fatty acids and retinol, while diets rich in carbohydrates and proteins, sodium, potassium are associated with an increase myopia risk: but this does not mean that nutritional deprivation is a remedy against myopia without presupposing a necessary causal link. In summary the problem of progression of myopia is complex and varied [23-25]: the rapid increase in myopia in the world requires explanations that go beyond genetics, with influences of the visual environment taking on an increasingly important role. The advent of electronic laptop technology, currently poorly standardizable, can provide key elements to clarify the epidemiology of myopia. The benefits of outdoor activity have offered a protective strategy on the incidence of myopia even if the mechanism remains unresolved. Further research on behavior, inside and outside, in closed and outdoor environments, will have to establish how much behavior and lifestyle must be modified to reduce the incidence and progression of myopia

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