Vitale et al. reported a substantial increase in the prevalence of myopia in the United States from 25.0% in 1971−1972 to 41.6% in 1999−2004 [32]. Williams et al. [33] reported an overall prevalence of myopia in Europe of 30.6%, with a particularly high prevalence of 47.2% among adults aged 25−29 years. These studies analyzed differences based on ethnicity and educational levels. Holden et al. [1] predicted that the global prevalence of myopia would increase from approximately 23% (1.4 billion people) in 2000 to approximately 49.8% (5 billion people) by 2050.

The prevalence of myopia among young adults in East Asia is higher than that in Western countries and other regions [11]. In China, Li et al. [34] investigated the annual incidence of myopia progression and high myopia in schoolchildren from grades 1 to 6. They reported a substantial increase in the prevalence of myopia: the annual incidence increased from 7.8% in grades 1 and 2 to 25.3% in grades 5 and 6, while the incidence of high myopia increased from 0.1% to 1.0%. In Taiwan, a nationwide population- based study examined the prospective association between near-visual activity and incident myopia in children aged 7–12 over a 4-year follow-up period. The study showed that 26.8% of the children had myopia at baseline in 2010, while 27.7% of those without myopia at baseline developed incident myopia in 2010–2013. Consequently, more than 50% of children developed myopia during adolescence [35].

The Korean National Health and Nutrition Examination Survey (KNHANES) conducted in a nationally representative cross-sectional cohort of 3,862 children showed that 2,495 of them (64.6%) had myopia, among whom 5.4% high myopia. The prevalence rate ratios (PRRs) for pediatric myopia and high myopia among children with myopic parents were 1.34 (95% confidence interval [CI], 1.24–1.45) and 3.11 (95% CI, 1.93–5.01), respectively. The PRRs of myopia and high myopia significantly increased to 1.37 (95% CI, 1.04–1.81) and 11.41 (95% CI, 6.24–20.88), respectively with higher degrees of parental myopia [36].

The pathophysiological evidence of myopia can be broadly categorized into anatomical and biological changes. Researches demonstrated that myopia arises primarily from excessive axial elongation, which is closely associated with scleral remodeling [3,39]. The molecular mechanisms underlying this increase in axial length have been studied extensively. Ku et al. [40] identified a role for transforming growth factor-β in the signaling pathways of myopia and axial elongation of enhancing intraocular inflammation. Liu and Sun reported that insulin-like growth factor-1/signal transducer and activator of the transcription 3 pathway in the sclera may modulate metalloproteinase-2 expression, thus playing an essential role in scleral remodeling during myopia development [41,42].

Changes in choroidal thickness are a characteristic structural feature of myopia. Experimental studies revealed that the choroid actively and rapidly regulates eye growth [43,44]. Rapid variations in choroidal thickness under defocused or deprived conditions suggest its important role in this mechanism. Based on clinical observations, Flores-Moreno et al. [45] reported that axial length was significantly associated with choroidal thickness in patients with high myopia. In fact, the choroidal thickness profile differed between individuals with high myopia and those with emmetropia.

A choroidal blood flow reduction is also closely associated with myopia, particularly high myopia [46,47]. The observed changes included reduced vessel diameter and increased vessel wall rigidity. A notable finding was the impact of hypoxia resulting from reduced choroidal blood flow on myopia progression as demonstrated in animal myopia models [48] and human scleral fibroblasts [49]. The above research suggests that oxygen deficiency can induce structural scleral changes, ultimately accelerating axial length elongation and myopia progression.

Dopamine receptors play a critical role in myopia development [50]. In several animal studies, activated D1 receptors demonstrated the potential to inhibit myopia development. D2 receptors exhibited a biphasic effect in which low doses suppressed and high doses promoted myopia progression. D4 receptors are associated with an increased susceptibility to form-deprived myopia.

A meta-analysis of European populations that combined data from 9 different cohort studies involving 16,830 participants in a myopia analysis and 14,981 in a hyperopia analysis identified significant genetic variants in 2 key regions, 8q12 and 15q14, associated with myopia and hyperopia [51]. Notably, this study successfully replicated 11 previously reported genetic loci associated with myopia [52]. This research demonstrated that certain genetic factors could influence the myopic and hyperopic pathways, although in opposing directions.

A genome-wide association study conducted of a Han Chinese population of 3,222 patients and 6311 controls investigated the genetic factors associated with high myopia [53]. Significant genetic variants were identified in the 13q12.12 region, which contains the MIPEP, C1QTNF9B-AS1, and C1QTNF9B genes. Of them, MIPEP and C1QTNF9B are expressed in the retina and retinal pigment epithelium, suggesting their roles in myopia development.

Parental genetic factors play a crucial role in myopia development and progression. Research indicates that children with 2 myopic parents have a greater than 3 to 6 times the risk of developing juvenile-onset myopia than those whose parents are not myopic [54,55]. Additionally, a prospective study of primary school children in Beijing, China, confirmed that parental myopia is a key factor that increases the risk of myopia among children [56]. Despite the consideration of variables such as parental myopia status, a child's near-work time, and academic achievement, parental myopia remained an independent risk factor [57]. More importantly, parental myopia affects age at myopia onset as well as progression in children. A study of Singaporean children revealed that earlier-onset myopia and parental high myopia significantly increased a child's risk of developing high myopia in later childhood [58]. The Correction of Myopia Evaluation Trial further confirmed this genetic influence, showing that children with 2 myopic parents experienced a significantly greater progression of myopia than those with one or no myopic parents. Notably, this parental effect was less pronounced in children wearing progressive addition versus single-vision lenses, suggesting potential interactions between genetic predisposition and treatment approach [59].

Li et al. identified a positive correlation between height and axial length, both of which are important factors in the development and progression of myopia [60]. Their study of preschool children aged 3–6 years from 10 randomly selected kindergartens revealed that taller children had longer axial lengths. Machluf et al. [61] reported an elevated risk of bilateral myopia associated with body mass index alone or with both height and weight in boys.

Obesity is associated with high myopia in children and adolescents. The National Health and Nutrition Examination Survey, which included 9008 adolescents in the USA, reported associations between weight, body mass index, and the occurrence of myopia [62]. The survey indicated that height and ethnicity correlated with degree of myopia.

The KNHANES showed that obese children and adolescents were 3.77-fold more likely to develop high myopia than normal-weight individuals. Significant sex-related differences were observed; obese girls had a 5.04-fold higher risk, whereas obese boys had a 2.84-fold higher risk. Researchers identified insulin resistance, which is present in 15%–20% of children with obesity, as a significant contributing factor [63].

A study in South Korea demonstrated that the odds of developing myopia were 41% lower among individuals sleeping more than 9 hours per night than among those sleeping less than 5 hours per night [64]. Additionally, Australian university students with myopia averaged 7.18 hours of sleep versus 8.46 hours in those without myopia [65]. In addition to sleep duration, bedtime was a significant factor, with several studies finding that later bedtimes are associated with myopia [66,67]. In contrast, a study in Singapore showed no independent association between sleep quality, duration, timing, or consistency of specific sleep factors and myopia in elementary school–aged children [68]. Another study showed that sleep duration and quality at 12 months of age were not associated with refractive error at 3 years of age [69]. Thus, further research is required to clarify the relationship between sleep patterns and myopia.

Yin et al. [70] reported that a balanced diet including meat, seafood, dairy products, eggs, legumes, vegetables, fruits, grains, and potatoes may protect against myopia. Kim and Choi [71] examined the role of diet and lifestyle choices in the development of myopia in children using data from 24,345 children aged 5–12 years from the KNHANES. They reported that children with myopia had significantly lower intakes of fat, omega-3 fatty acids, and retinol but higher intake of other nutrients relative to their emmetropic and hyperopic counterparts. High dietary levels of carbohydrates, proteins, phosphorus, iron, potassium, and sodium have been associated with an increased risk of myopia. Notably, a high sodium intake was associated with a 2.05-fold higher risk of myopia.

The consumption of foods with a high glycemic index has also been associated with the development of myopia. Cordain et al. [72] reported that the excessive intake of such foods promotes insulin resistance, while the resulting elevation in blood insulin levels stimulates insulin-like growth factor 1 secretion, which can increase axial length and contribute to myopia development. Conversely, fruit consumption may protect against myopia. Zhang et al. [73] reported that the phytochemicals in fruits, particularly carotenoids, may help prevent myopia.

A link between salt intake and myopia was recently established. Dietary sodium chloride increases the ionic permeability of the retinal membranes, leading to fluid accumulation in the vitreous. This process stretches the ocular tissue, ultimately resulting in axial myopia [74].

Spectacles are conventional optical devices that are used to correct refractive errors. In animal experiments using chicks, monocular deprivation of form vision caused myopia and increased axial length [75], suggesting that spectacles that appropriately correct refractive errors can primarily help inhibit the progression of myopia. Human clinical studies demonstrated that the accurate prescription of spectacles and regular follow-up of refractive error monitoring are important for myopia management, including cases of myopia-induced amblyopia [76]. Spectacles are not associated with vision-threatening complications or systemic side effects, making them a safe primary approach. However, spectacles alone cannot effectively prevent the progression of myopia. Several recent studies demonstrated that defocus-incorporated multisegment spectacle (DIMS) lenses can effectively control myopia [77-81]. DIMS lenses consist of a central distance optical zone (diameter, 9 mm) surrounded by an annular midperipheral zone containing 396 small round segments (diameter, approximately 1.03 mm), each with a +3.50 D add power. These lenses allow clear central vision while introducing myopic defocus into the peripheral retina [77,82]. As described above in the Possible Mechanism of Myopia Progression section, myopic and hyperopic defocus are complementary theories that explain how the position of the focal point of the retina regulates eye growth (Fig. 2). Hyperopic defocus (focusing in front of the retina) promotes eye growth and exacerbates myopia, whereas myopic defocus (focusing behind the retina) inhibits eye growth and slows the progression of myopia, demonstrating the bidirectional actions of the same visual feedback system.

Orthokeratology is a nonsurgical procedure that uses specially designed contact lenses to temporarily reshape the cornea during sleep and improve an individual's vision. The design of the orthokeratology lens creates controls pressure on the central cornea, thereby flattening this area. This geometric modification produces the refractive power change required for myopia correction. The pressure exerted by the lens causes the corneal epithelial cells to migrate from the central to peripheral cornea, leading to thinning of the central corneal region while simultaneously thickening the peripheral areas and effectively reshaping the corneal surface. During this process, the tear layer between the lens and the cornea generates hydrodynamic forces that facilitate corneal molding [83-85]. The correction of myopia up to -6.0 D is achieved through central corneal epithelial thinning and midperipheral epithelial and stromal thickening. Recent studies reported that orthokeratology effectively slows the progression of myopia by preventing axial length elongation [14,86-89].

However, orthokeratology can occasionally cause acanthamoeba keratitis [90,91] or bacterial keratitis [92,93] when lens management is inadequate; these conditions are more common in children and adolescents [94]. Despite early intervention and treatment, most infections result in the formation of corneal scars; almost 10% of affected eyes require surgical treatment [94]. Therefore, daily lens cleaning and disinfection protocols, including rubbing and rinsing lenses with prescribed solutions prior to storage, are strictly recommended [95].

Rebounding, which presents another challenge in orthokeratology, is defined as the accelerated progression of myopia that occurs after the discontinuation of any myopia control treatment [96-100]. Cho and Cheung [96] found that stopping orthokeratology at or before 14 years of age led to a more rapid increase in axial length compared to those wearing spectacles and those in continuous orthokeratology groups. However, axial elongation slowed again with the resumption of orthokeratology after 6 months. Therefore, if orthokeratology treatment begins before 14 years of age, it is crucial to select children who can maintain treatment consistency [100]. However, the optimal treatment duration and progressive reduction strategies to prevent the progression of myopia require further investigation.

Conversely, myopia undercorrection, blue light–blocking glass use, and rigid gas-permeable contact lens wear have no or minimal effects on myopia progression [101-105].

Atropine nonselectively blocks muscarinic receptors located in the human ciliary muscle, retina, and sclera [106]. Although the precise mechanism of atropine in myopia control remains unknown, it is thought to act directly or indirectly on the retina or sclera, inhibiting scleral thinning or stretching and thereby preventing eye growth [107-113].

Research on diluted atropine eye drops in Taiwan led to significantly improved myopia control. The Atropine for the Treatment of Myopia clinical trials in particular influenced this field. Chia et al. [114] demonstrated that different concentrations of atropine exhibited varying degrees of efficacy at controlling myopia progression.

The Low-Concentration Atropine for Myopia Progression study provided critical evidence of the efficacy of low-concentration atropine. The 0.05%, 0.025%, and 0.01% atropine eye drops effectively controlled myopia progression in a concentration-dependent manner [115]. Additionally, 0.05% atropine offers an optimal balance between efficacy and side effects, with minimal rebound effects after its discontinuation [116,117].

Through large-scale studies demonstrating effective results, low-concentration atropine eye drops have become the preferred treatment for controlling myopia progression.

However, atropine eye drops exhibit several adverse effects. Pupil dilation can cause photophobia, leading to discomfort upon exposure to bright light [115] and near-vision reduction, although these effects are often minimal at low doses [118,119]. If atropine passes through the puncta into the nasolacrimal duct and is subsequently absorbed through the nasal mucosa, it can carry systemic side effects such as dry mouth, flushing, drowsiness, and tachycardia [107,120,121]. Therefore, even at low concentrations, it is necessary to take precautions to prevent systemic side effects by compressing the puncta with the fingers for some time after eyedrop instillation.

Atropine eye drops can also lead to rebound [97]. When high-concentration atropine eye drops (0.5% and 0.1%) were used, a rapid progression of myopia was observed after discontinuation [98]. However, no significant rebound was observed when low-concentration atropine eye drops (0.025% and 0.01%) were used for 2 years and then discontinued. With 0.05% atropine eye drops, faster axial growth (0.04 mm) was observed during the first year postdiscontinuation, which was considered clinically insignificant. Moreover, children aged 6–8 years showed similar rates of eye growth postdiscontinuation all concentrations (0.05%, 0.025%, 0.01%) [99]. Based on the research conducted to date, the recommendation involves using either use low-concentration atropine eye drops (0.025%, 0.01%) from the beginning, or for those using higher concentrations, gradually tapering down to low-concentration atropine eye drops and maintaining this regimen for at least 2 years to help prevent rebound.

Numerous studies have established an association between near work and myopia progression. Recent systematic reviews and meta-analyses have suggested that the increased use of digital devices such as smartphones and tablets is linked to a higher risk of myopia. Specifically, increased digital device use was associated with a 1.26-fold (95% CI, 1.00–1.60) higher risk of myopia; total digital screen time, including computer use, was associated with a 1.77-fold (95% CI, 1.28–2.45) higher risk [122]. Near-work activities performed at distances shorter than 20 cm significantly increase the risk of myopia development [123,124]. These findings suggest that near-work activities, including digital device use, are significant environmental risk factors for the progression of myopia in children and adolescents.

Outdoor activities are an important strategy in the management of myopia progression. Rose et al. [125] reported that at least 2 hours of daylight exposure can help prevent the onset of myopia in children of myopic parents who do not yet have myopia. The Family Incentive Trial in Singapore confirmed that weekend outdoor intervention programs significantly increased children's outdoor time. These findings suggest that structured outdoor activities can prevent myopia prevention in children [126]. In addition, a Taiwanese study of 571 children aged 7–11 years showed that the Recess Outside the Classroom Program significantly reduced the incidence of myopia in the intervention versus control group. Among the nonmyopic participants, the progression of myopia was significantly lower in the intervention group [127].

Research regarding this relationship was conducted during the coronavirus disease 2019 pandemic, when outdoor activities were restricted. Two studies revealed a significant myopic shift and increased prevalence of myopia during this period, particularly among children [10,128]. Another study demonstrated that daily digital device use increased from 0.67 to 5.24 hours per day; faster progression was observed in children using phones and tablets versus those using televisions or projectors [129].

Additionally, regarding nonophthalmological conditions, as mentioned in the relationship between nonophthalmological conditions and myopia in children and adolescents section, adequate sleep duration and regular sleep patterns, along with a healthy body weight and an appropriate diet (including reduced sodium intake and increased fruit consumption), are thought to help prevent myopia.