Myopia
Myopia, commonly known as nearsightedness, is a common vision condition where distant objects appear blurry while close objects are clear. It primarily results from an abnormal increase in the eye’s axial length, the distance between the anterior and posterior poles of the eye globe. A 1 millimeter increase in axial length can lead to a myopic shift of 2.00 to 3.00 diopters, assuming no changes in the optical power of the cornea and lens. High myopia is typically defined as an ocular spherical equivalent refraction below -6.00 diopters and is associated with a significantly elongated axial length. The prevalence of myopia is notably higher in Asian populations compared to other parts of the world[1], and its development is influenced by both environmental factors, such as extensive near work and higher education, and genetic predispositions [2].
The biological basis of myopia involves a complex interplay of genetic and environmental factors. Genetic factors contribute significantly to its development, especially in cases of pathological myopia[2]. Twin studies have indicated a high heritability for refractive error and axial length, estimated to be up to 0.90, although these estimates might be influenced by shared environmental effects [2]. Whole-genome linkage analyses have identified at least 16 susceptible chromosomal loci (MYP1–16) associated with myopia[2]. Genome-Wide Association Studies (GWAS) have emerged as a powerful tool to identify causal genetic variants by screening millions of single nucleotide polymorphisms (SNPs) across the genome[3]. These studies have successfully identified numerous genetic variants linked to myopia. For instance, a genome-wide meta-analysis confirmed the replication of 11 loci associated with myopia and hyperopia[4]. Specific genetic regions implicated include chromosome 1q41, which influences ocular axial length and high myopia[1], a susceptible locus for pathological myopia at 11q24.1[2], and variants at 13q12.12 associated with high myopia in the Han Chinese population[5]. Furthermore, genetic variants in CTNND2have been associated with high myopia in Singapore Chinese[3], and research suggests that light-induced signaling pathways are key drivers for refractive error [6].
Clinically, myopia increases the risk of various visual morbidities[1]. Pathological myopia, characterized by excessive axial elongation and degenerative changes within the eye, represents a leading cause of irreversible visual impairment[2]. The significant impact of myopia on vision and ocular health underscores its clinical relevance.
From a societal perspective, myopia poses a substantial public health burden, particularly in regions with high prevalence like Asia[1]. Given the significant role of genetic factors in its development, identifying the specific genetic determinants of myopia is an urgent and important task, crucial for developing effective prevention strategies and treatments[2].
Limitations
Section titled “Limitations”Understanding the genetic architecture of myopia is a complex endeavor, and current research, while making significant strides, operates within several key limitations. These limitations pertain to study methodologies, the diverse nature of myopia itself, and the intricate interplay of genetic and environmental factors. Acknowledging these challenges is crucial for interpreting findings and guiding future research directions.
Methodological and Statistical Considerations
Section titled “Methodological and Statistical Considerations”Genetic studies of myopia, particularly early genome-wide association studies (GWAS), often face challenges related to sample size and statistical power. Although meta-analyses help to increase power and identify robust associations[4], initial findings can sometimes suffer from effect-size inflation, where the magnitude of genetic effects might be overestimated in smaller discovery cohorts[7]. This necessitates rigorous replication in independent populations to validate associations and provide more accurate estimates of genetic influence [8].
The process of identifying and confirming genetic loci for myopia is further complicated by the need for stringent statistical thresholds to account for multiple testing across the genome. This can lead to some true associations being missed or requiring very large cohorts to reach genome-wide significance, as evidenced by studies where SNPs were not significantly associated after correction for multiple testing[5]. Consequently, while significant progress has been made, the true landscape of genetic susceptibility may be broader than currently recognized, with many variants having small individual effects that are difficult to detect consistently without extensive international collaborations.
Phenotypic Heterogeneity and Population Specificity
Section titled “Phenotypic Heterogeneity and Population Specificity”The definition and measurement of myopia present a notable challenge, as the condition can be characterized by varying degrees of spherical equivalent refraction or ocular axial length, and studies may focus on different subtypes like common, high, or pathological myopia[1]. This phenotypic heterogeneity means that genetic variants associated with one form of myopia might not be equally relevant or impactful for another, complicating comparisons and meta-analyses across studies. Furthermore, the precise relationship between refractive error and axial length (e.g., a 1mm increase in axial length is equivalent to a myopic shift of -2.00 to -3.00 diopters)[1] highlights the importance of consistent and accurate ophthalmic measurements, which can vary between cohorts.
Another significant limitation lies in the generalizability of findings across diverse ancestral populations. Myopia prevalence is notably higher in Asian populations compared to other parts of the world[1], and many genetic studies have focused on specific groups, such as the Han Chinese [5] or Singapore Chinese populations [3]. While these studies identify important population-specific loci, the genetic architecture of myopia may differ significantly across ancestries, meaning that variants identified in one population may not fully explain the heritability or risk in others. This calls for broader, multi-ethnic investigations to ensure a comprehensive understanding of myopia genetics globally.
Complex Etiology and Unexplained Variation
Section titled “Complex Etiology and Unexplained Variation”Myopia is a complex multifactorial trait, and current genetic models often do not fully account for the substantial influence of environmental factors and gene-environment interactions. For instance, light-induced signaling has been highlighted as a driver for refractive error[6], indicating that lifestyle and environmental exposures play a crucial role alongside genetic predispositions. Disentangling these complex interactions is challenging, as the effect of genetic variants might be modulated by specific environmental contexts, leading to varying phenotypic expression and incomplete heritability estimates from purely genetic studies.
Despite the identification of numerous genetic loci, a significant portion of myopia’s heritability remains unexplained, a phenomenon often referred to as “missing heritability.” While genetic risk scores (GRS) derived from identified variants can capture some risk, such as those derived from 71 out of 140 genome-wide significant lead variants[9], they do not fully predict an individual’s susceptibility. This suggests that many more common variants with very small effects, rare variants, structural variations, or epigenetic modifications may contribute to myopia risk, necessitating further research to fully elucidate the genetic landscape and the underlying biological mechanisms. The current understanding of specific gene functions and their pathways in ocular development and refractive error progression is still evolving, representing a significant knowledge gap.
Variants
Section titled “Variants”Genetic variations play a significant role in determining an individual’s susceptibility to myopia by influencing various aspects of eye development, structure, and function. Studies have identified several genes and their specific variants (single nucleotide polymorphisms, or SNPs) that are consistently associated with myopia and related traits like ocular axial length. These genes often regulate processes crucial for the eye’s growth and its ability to focus light.
The LAMA2 gene, located on chromosome 6, encodes laminin alpha 2, a critical component of the extracellular matrix that provides structural integrity and signaling cues in various tissues, including those of the eye. A specific variant, rs12193446 , has been associated with myopia and ocular axial length, suggesting its role in the biomechanical properties of the sclera or in retinal development[4] Similarly, variants within GJD2, such as rs524952 , rs634990 , and rs589135 , are found on chromosome 15 and have shown associations with myopia and refractive error[4]GJD2 encodes connexin 36, a protein forming gap junctions vital for direct cell-to-cell communication, particularly in the retina where it facilitates signal transmission between neurons, impacting visual processing and potentially scleral remodeling. The potassium voltage-gated channel subfamily Q member 5 (KCNQ5) gene, located on chromosome 6, includes variants likers7744813 that are significantly associated with myopia[4] KCNQ5 channels regulate neuronal excitability and neurotransmitter release, and their proper function is critical for maintaining retinal photoreceptor and neuronal activity, suggesting that variations may influence ocular growth and refractive development.
The RBFOX1 gene, found on chromosome 16, contains variants such as rs10500355 , rs17648524 , and rs7184522 , with rs17648524 being specifically noted in myopia association studies[4] RBFOX1 is an RNA binding protein that regulates alternative splicing of numerous target genes, playing a key role in neuronal development and function, which could impact the neural pathways involved in eye growth regulation. Variants including rs11606250 and rs11602008 near LRRC4C, located on chromosome 11, have been identified in genome-wide association studies for myopia[4]LRRC4C encodes a leucine-rich repeat containing protein involved in cell adhesion and signaling, particularly in neuronal structures, suggesting its involvement in the complex cellular interactions that govern ocular development and refractive state. PRSS56, a gene on chromosome 2, with variants likers1550094 , is linked to myopia and ocular axial length[4]This gene encodes a serine protease that is thought to be involved in ocular development and the maintenance of scleral integrity, with its dysfunction potentially contributing to the excessive eye elongation characteristic of myopia.
The ZMAT4 gene, located on chromosome 8, and its associated variants such as rs7829127 , rs869422 , rs72644322 , and rs10089517 , have been consistently identified in studies on myopia and ocular axial length[4] ZMAT4 encodes a zinc finger matrin-type protein involved in nuclear matrix organization and gene expression regulation, which could influence the development and growth of ocular tissues [4] Variants within the RDH5 gene, including rs3138141 and rs3138142 , are implicated in the visual cycle, a process critical for converting light into electrical signals in the retina. RDH5 encodes retinol dehydrogenase 5, an enzyme primarily expressed in the retinal pigment epithelium, responsible for processing retinoids essential for photoreceptor function. The SHISA6 gene, with variants like rs2908972 , rs113941606 , and rs2969185 , plays a role in modulating receptor trafficking and synaptic function in the nervous system. While its direct link to myopia mechanisms is still being explored, its involvement in neuronal signaling pathways suggests a potential influence on visual processing and the neural feedback loops that control eye development.
Key Variants
Section titled “Key Variants”| RS ID | Gene | Related Traits |
|---|---|---|
| rs12193446 | LAMA2 | refractive error, self reported educational attainment axial length measurement Hypermetropia myopia eye disease |
| rs524952 rs634990 rs589135 | LINC02252 - GJD2 | refractive error, self reported educational attainment Abnormality of refraction myopia eye disease refractive error |
| rs11606250 rs11602008 | LRRC4C | myopia eye disease Abnormality of refraction Hypermetropia |
| rs10500355 rs17648524 rs7184522 | RBFOX1 | Abnormality of refraction myopia cataract |
| rs7744813 rs6929347 rs951762 | KCNQ5 | refractive error, self reported educational attainment Abnormality of refraction myopia eye disease cataract |
| rs3138141 rs3138142 | RDH5 | atrophic macular degeneration, age-related macular degeneration, wet macular degeneration myopia age-related macular degeneration, COVID-19 retinopathy degeneration of macula and posterior pole |
| rs72621438 rs10089517 rs11777176 | TOX-DT - RNA5SP267 | myopia refractive error retinal vasculature measurement age at onset, eye measurement Abnormality of refraction |
| rs1550094 | PRSS56 | myopia retinal vasculature measurement refractive error age at onset, eye measurement Abnormality of refraction |
| rs2908972 rs113941606 rs2969185 | SHISA6 | refractive error, self reported educational attainment myopia Abnormality of refraction refractive error Hypermetropia |
| rs7829127 rs869422 rs72644322 | ZMAT4 | Abnormality of refraction myopia |
Classification, Definition, and Terminology
Section titled “Classification, Definition, and Terminology”Myopia, commonly known as nearsightedness, is a widespread ocular disorder characterized by a refractive error where parallel light rays entering the eye converge and focus in front of the retina, rather than directly on it, leading to blurred distant vision[2]. This condition primarily stems from an abnormal elongation of the ocular axial length (AL), which is the physical distance between the anterior and posterior poles of the eye globe [1], [2]. While the roles of corneal curvature and lens thickness are considered minimal, an increased AL is the most significant anatomical contributor to myopic refraction [1].
The extent of myopia is quantitatively measured in diopters (D) of spherical equivalent (SE) refraction, reflecting the optical power needed for correction[1], [4]. There is a direct correlation between axial length and refractive power: an increase in axial length by approximately 1 millimeter (mm) typically corresponds to a myopic shift of 2.00 to 3.00 D, assuming no compensatory alterations in the optical power of the cornea and lens [1], [2]. This fundamental relationship highlights axial length as a critical parameter for both conceptual understanding and clinical measurement of myopia.
Classification and Severity Grading
Section titled “Classification and Severity Grading”Myopia is broadly categorized into two distinct subsets: common myopia (also termed low or moderate myopia) and pathological myopia (also known as high myopia)[2]. This classification is vital due to differences in their clinical implications and risks. Pathological myopia is specifically differentiated from common myopia by an excessive increase in the axial length of the eyeball, which is the primary determinant of the severe refractive error[2].
High myopia is clinically defined by an ocular spherical equivalent (SE) refraction of -6.00 D or less[1]. Pathological myopia is further characterized by an axial length exceeding 26.0 mm, which generally corresponds to a refractive error greater than -6 D[2]. This severe form, which affects 1% to 5% of the population, is associated with unique and sight-threatening degenerative changes at the posterior pole of the eye, such as chorioretinal atrophy and posterior staphyloma [2]. These degenerative changes can lead to irreversible visual impairment and are a leading cause of legal blindness in developed countries[2].
Diagnostic Criteria and Associated Terminology
Section titled “Diagnostic Criteria and Associated Terminology”The diagnosis and classification of myopia in both clinical and research settings rely on precise measurements of ocular parameters, predominantly spherical equivalent (SE) refraction and axial length (AL). For instance, in studies, myopic cases in children aged 10 to 12 years have been operationally defined by an SE of -6.00 D or less in at least one eye, with controls having an SE of +1.00 D or more in both eyes[1]. A commonly adopted criterion for identifying myopia cases in general populations is an SE of -6.00 D or less in either eye[1].
The accurate measurement of these critical parameters is achieved through standardized ophthalmological techniques. Axial length is typically determined using applanation A-scan ultrasonography or partial coherence interferometry, often with devices like the IOLMaster [2]. Key terms in the nomenclature of myopia include “refractive error,” “diopters (D)” to quantify refractive power, and “ocular axial length (AL)” to describe the eye’s physical dimension[1], [2]. Furthermore, specific terms such as “chorioretinal atrophy” and “posterior staphyloma” are used to describe the characteristic degenerative changes observed in pathological myopia, underscoring its distinct clinical manifestations[2].
Signs and Symptoms
Section titled “Signs and Symptoms”Myopia, commonly known as nearsightedness, is a prevalent refractive error where parallel rays of light focus in front of the retina, resulting in blurred vision for distant objects.[2] This condition is one of the most common ocular disorders globally, exhibiting significant variability in prevalence across populations; for instance, it affects approximately 40% of East Asian (Chinese and Japanese) populations, compared to about 25% in Caucasian populations. [2]Myopia presents across a spectrum of severity, broadly categorized into common (low/moderate) myopia and pathological (high) myopia, primarily distinguished by the degree of ocular axial length increase and the presence of associated ocular pathologies.[2]
Clinical Presentation and Refractive Characteristics
Section titled “Clinical Presentation and Refractive Characteristics”The primary clinical manifestation of myopia is an abnormal increase in ocular axial length (AL), which is the distance between the anterior and posterior poles of the eye globe. The contribution of corneal curvature and lens thickness to myopic refraction is considered minimal.[1] This elongation of the eyeball directly correlates with the severity of the refractive error; a 1 millimeter (mm) increase in axial length is equivalent to a myopic shift of approximately 2.00 to 3.00 diopters (D) when there are no corresponding changes in the optical power of the cornea and lens. [1] In adults, the typical axial length of the eyeball is around 24 mm. [2] The subjective symptom of blurred distant vision is the most common presenting complaint, often leading individuals to seek ophthalmic evaluation.
Diagnostic Measurement and Severity Classification
Section titled “Diagnostic Measurement and Severity Classification”The diagnosis and classification of myopia rely on objective measurement approaches, primarily assessing the spherical equivalent (SE) refractive error and ocular axial length. High myopia is often defined by an ocular spherical equivalent refraction below 26.00 D[1] or by an axial length exceeding 26.0 mm, which is stated to be equivalent to refractive errors greater than 26 D. [2]The distribution of axial lengths within the adult myopic population can be bimodal, with the subgroup demonstrating significantly elongated axial lengths corresponding to pathological myopia.[2] This subgroup, characterized by extreme axial elongation, represents 1% to 5% of the general population and necessitates careful monitoring. [2]Precise measurement of both spherical equivalent refraction and axial length serves as a critical diagnostic tool, guiding the classification of myopia and informing clinical management strategies.
Phenotypic Diversity and Prognostic Indicators
Section titled “Phenotypic Diversity and Prognostic Indicators”Myopia exhibits significant phenotypic diversity, particularly evident in the distinction between common and pathological forms. Pathological myopia is characterized by an excessive axial elongation of the eyeball, which induces mechanical strain on ocular tissues, leading to subsequent degenerative changes in the retina, choroid, and sclera.[2]Key diagnostic indicators, or “red flags,” unique to pathological myopia include degenerative changes at the posterior pole of the eye, such as chorioretinal atrophy or posterior staphyloma.[2]These specific degenerative changes are prognostically significant as they often result in uncorrectable visual impairment due to decreased central vision, making pathological myopia a leading cause of legal blindness in developed countries.[2]The development of myopia, especially its pathological form, is influenced by both environmental factors like extensive near work and higher education, and genetic factors, highlighting the complex and heterogeneous nature of its presentation.[2]
Causes
Section titled “Causes”Genetic Predisposition
Section titled “Genetic Predisposition”Myopia is strongly influenced by genetic factors, with twin studies estimating the heritability of refractive error and axial length to be as high as 90%[2]. This complex trait involves multiple inherited variants, contributing to a polygenic risk profile, although family-based linkage analyses have identified at least 16 susceptible chromosomal loci (MYP1–16) [2]. Genome-wide association studies (GWAS) have further pinpointed specific genetic regions, including 11 loci replicated in meta-analyses, and chromosome 1q41, which significantly influences ocular axial length and high myopia[4]. Other identified genetic markers include a novel susceptible locus for pathological myopia at 11q24.1 and variants inCTNND2associated with high myopia[2].
Environmental and Lifestyle Influences
Section titled “Environmental and Lifestyle Influences”Beyond genetics, environmental and lifestyle factors play a crucial role in myopia development. Extensive near work and higher education levels have been identified as significant contributors to the condition[2]. These factors suggest that prolonged engagement in visually demanding tasks, often associated with academic or professional pursuits, can exacerbate the risk of myopia. Geographic location and socioeconomic status also influence prevalence, with significantly higher rates observed in certain regions, particularly in Asia, highlighting the impact of societal and behavioral patterns on ocular health[1].
Interplay of Genetics and Environment
Section titled “Interplay of Genetics and Environment”The development of myopia is often a result of intricate gene-environment interactions, where an individual’s genetic predisposition is modulated by external triggers. Studies have shown that both genetic and environmental factors contribute to the development of myopia, particularly pathological myopia[2]. This indicates that while certain individuals may carry genetic variants increasing their susceptibility, the manifestation and severity of myopia can be significantly influenced by environmental exposures. Understanding these complex gene-environment effects is critical for comprehensive risk assessment and the development of targeted preventative strategies[4].
Ocular Development and Structural Changes
Section titled “Ocular Development and Structural Changes”The primary anatomical cause of human myopia is an abnormal increase in ocular axial length (AL), which is the distance between the anterior and posterior poles of the eye globe[1]. This excessive elongation of the eye globe is the key developmental change, with a 1-millimeter increase in axial length corresponding to a significant myopic shift of 2.00 to 3.00 diopters [1]. While corneal curvature and lens thickness play only a minimal role, an abnormally long axial length is particularly characteristic of high myopia, defined as an ocular spherical equivalent refraction below -6.00 D[1]. Understanding the developmental mechanisms that regulate eye growth and lead to this axial elongation is central to comprehending myopia’s progression.
Ocular Axial Elongation and Pathological Consequences
Section titled “Ocular Axial Elongation and Pathological Consequences”Myopia is predominantly characterized by an abnormal increase in ocular axial length (AL), the distance between the anterior and posterior poles of the eye globe, with minimal contributions from corneal curvature or lens thickness[1]. A 1 millimeter increase in AL can lead to a significant myopic shift of approximately -2.00 to -3.00 diopters (D) [1]. High myopia, often defined by a spherical equivalent refraction below -6.00 D, is intrinsically linked to an abnormally elongated AL[1].
A distinct subgroup, pathological myopia, represents 1% to 5% of the population and is characterized by an axial length exceeding 26.0 mm, corresponding to refractive errors greater than -6 D[2]. This excessive ocular elongation induces mechanical strain, leading to severe degenerative changes in the retina, choroid, and sclera [2]. Clinically significant changes at the posterior pole, such as chorioretinal atrophy and posterior staphyloma, are unique to pathological myopia and can result in uncorrectable visual impairment, making it a leading cause of legal blindness[2].
Genetic Contributions and Identified Loci
Section titled “Genetic Contributions and Identified Loci”Myopia development is influenced by both environmental factors, such as near work, and significant genetic contributions, particularly for pathological myopia[2]. Twin studies have estimated the heritability of refractive error and axial length to be as high as 0.90, underscoring the strong genetic predisposition, although common environmental effects might lead to overestimation [2]. Early family-based whole genome linkage analyses have identified at least 16 susceptible chromosomal loci, termed MYP1-MYP16, associated with myopia[2].
Recent genome-wide association studies (GWAS) and meta-analyses have further elucidated the genetic landscape, replicating 11 loci associated with myopia and hyperopia[4]. Specific genetic variants on chromosome 1q41 have been found to influence ocular axial length and contribute to both common and high myopia[1]. Additionally, a novel susceptible locus for pathological myopia has been identified at 11q24.1[2], and variants at 13q12.12 are associated with high myopia in certain populations[5]. The gene CTNND2 (Catenin Delta 2) has also been implicated in high myopia[3].
Molecular Pathways and Cellular Processes
Section titled “Molecular Pathways and Cellular Processes”At the molecular level, abnormalities in retinal development, Wnt signaling pathways, and glucose metabolism are emerging as potential underlying mechanisms contributing to susceptibility to various ocular diseases, including myopia[10]. These pathways are critical for cell proliferation, differentiation, and tissue maintenance within the eye. Disruptions in these regulatory networks can impair the homeostatic balance required for normal ocular growth and development.
Studies in experimental mouse models of myopia, induced by minus lenses, have shown significant changes in axial length and refraction, with subsequent analyses focusing on gene expression within specific eye tissues[1]. Total RNA is isolated from the neural retina, retinal pigment epithelium (RPE), and sclera, indicating these tissues are key sites for molecular and cellular changes that drive ocular elongation [1]. The involvement of genes like CTNND2 suggests roles in cell adhesion, cytoskeletal regulation, and signaling, which are crucial for maintaining tissue integrity and regulating growth in the ocular wall [3].
Pathways and Mechanisms
Section titled “Pathways and Mechanisms”Genetic Underpinnings and Regulation of Ocular Development
Section titled “Genetic Underpinnings and Regulation of Ocular Development”Myopia is strongly influenced by genetic factors, with numerous loci identified that impact ocular axial length and disease susceptibility. Genome-wide meta-analyses have replicated 11 loci associated with myopia and hyperopia, while specific studies have pinpointed variants on chromosome 1q41, 11q24.1, 13q12.12, and within theCTNND2gene as influencing axial length and high myopia[4]. These genetic variants likely play a crucial role in regulating gene expression and the activity of transcription factors essential for proper ocular development. Dysregulation of these gene regulatory networks can lead to abnormalities in retinal development and the uncontrolled elongation of the eye, which is the hallmark of myopia[10].
Wnt signaling represents a critical pathway implicated in ocular development and disease susceptibility. Abnormalities in Wnt signaling are recognized as potential underlying mechanisms contributing to various ocular diseases, including myopia[10]. This pathway involves a complex cascade of receptor activation and intracellular signaling, ultimately modulating gene transcription that guides cellular proliferation, differentiation, and tissue patterning during eye growth. Perturbations in these tightly controlled signaling events can lead to structural changes, such as increased axial length, thereby predisposing individuals to myopia.
Environmental Signaling and Intracellular Cascades
Section titled “Environmental Signaling and Intracellular Cascades”Environmental factors, particularly light exposure, play a significant role in modulating refractive error through specific signaling pathways within the eye. Light-induced signaling has been highlighted as a key driver for refractive error, suggesting that the eye actively processes visual input to regulate its growth [6]. This process involves the activation of photoreceptors and other light-sensitive cells, which in turn initiate intricate intracellular signaling cascades. These cascades likely involve a series of molecular interactions, leading to downstream effects on cellular behavior and tissue remodeling that influence the rate of axial length elongation.
Dysregulation within these light-induced signaling pathways, or an imbalance in their feedback loops, can disrupt the fine-tuned control of ocular growth. For instance, altered patterns of light exposure or impaired cellular responses to light signals could lead to a persistent drive for axial elongation. Such disruptions in intracellular signaling cascades represent a crucial mechanistic link between environmental stimuli and the development or progression of myopia.
Metabolic Pathways and Ocular Homeostasis
Section titled “Metabolic Pathways and Ocular Homeostasis”Metabolic pathways are fundamental to maintaining ocular health and are increasingly recognized for their role in myopia pathogenesis. Abnormalities in glucose metabolism, for example, have been identified as potential underlying mechanisms contributing to susceptibility to multiple ocular diseases, including myopia[10]. The eye, particularly the retina, is metabolically highly active, requiring a constant supply of energy and precursors for biosynthesis.
Dysregulation in energy metabolism, altered biosynthesis of extracellular matrix components, or abnormal catabolism within ocular tissues can compromise the structural integrity and growth control of the eye. Imbalances in metabolic regulation and flux control could lead to cellular stress, impaired tissue repair, or altered biomechanical properties of the sclera, ultimately contributing to the abnormal increase in ocular axial length observed in myopia.
Integrated Network Dysregulation in Myopia Progression
Section titled “Integrated Network Dysregulation in Myopia Progression”The development of myopia is not typically attributed to a single pathway defect but rather to the intricate interplay and crosstalk among multiple molecular networks. Genetic predispositions, environmental light signals, and metabolic states are integrated through complex network interactions that collectively govern ocular growth. For instance, genetic variants might influence the sensitivity of light-induced signaling or the efficiency of glucose metabolism, creating a systems-level vulnerability to axial length elongation[10].
This pathway crosstalk and hierarchical regulation mean that dysregulation in one system, such as Wnt signaling or glucose metabolism, can have cascading effects across other pathways, leading to an emergent property of uncontrolled axial growth. Understanding these integrated network interactions and identifying key points of pathway dysregulation is critical for uncovering potential compensatory mechanisms and developing targeted therapeutic strategies for myopia[10].
Population Studies
Section titled “Population Studies”Population studies are fundamental to understanding the epidemiology, prevalence, and underlying risk factors for myopia across diverse groups. These large-scale investigations provide critical insights into temporal trends, geographic variations, and the complex interplay of genetic and environmental influences on this common vision condition.
Global Prevalence and Temporal Trends
Section titled “Global Prevalence and Temporal Trends”Myopia prevalence exhibits significant global variation and has demonstrated marked increases over several decades, highlighting a substantial public health challenge. Studies have documented an increased prevalence of myopia in the United States between 1971–1972 and 1999–2004[11], indicating a notable temporal shift. Similarly, longitudinal research in Taiwanese schoolchildren revealed rising prevalence rates from 1983 to 2000 [12]. These findings underscore the dynamic nature of myopia epidemiology, suggesting that changing environmental factors, alongside genetic predispositions, are contributing to its growing burden.
Epidemiological research has characterized myopia prevalence across diverse demographic groups and geographic regions. Analyses have examined the prevalence of refractive errors among adults in the United States, Western Europe, and Australia[13]. Further studies have specifically investigated urban children in southern China [14], populations in Hong Kong [15], and rural Korean populations [16], revealing varied rates and potential associations with different living environments and age groups. An adult inner-city population also showed distinct prevalence and risk factors [17], illustrating the multifaceted epidemiological landscape of myopia.
Cross-Population and Ancestry Variations
Section titled “Cross-Population and Ancestry Variations”Significant cross-population and ancestry differences in myopia prevalence are consistently observed, with Asian populations generally experiencing a notably higher prevalence compared to other parts of the world[1]. For instance, the Copenhagen City Eye Study provided detailed data on the prevalence and causes of visual impairment and blindness among 9980 Scandinavian adults[18], presenting a regional epidemiological profile distinct from those observed in Asian populations. These geographic and ethnic variations emphasize the necessity of population-specific research to fully elucidate the complex genetic and environmental determinants of myopia.
Further investigations have highlighted population-specific genetic effects and prevalence patterns, particularly concerning high myopia. Defined by an ocular spherical equivalent refraction below -6.00 D, high myopia is associated with abnormally long axial length and demonstrates particular aggregation within specific ethnic groups[1]. Genome-wide association studies (GWAS) have identified genetic loci, such as those at 13q12.12, associated with high myopia in the Han Chinese population[5], suggesting distinct genetic predispositions within different Asian ancestries. The Rotterdam Study, a large cohort study, contributed age-specific prevalence data from an older population, enriching the understanding of how myopia manifests across diverse demographic strata[19].
Large-Scale Genetic Epidemiology and Methodological Approaches
Section titled “Large-Scale Genetic Epidemiology and Methodological Approaches”Large-scale genetic epidemiology, often employing genome-wide association studies (GWAS) and meta-analyses, has been instrumental in identifying genetic loci associated with myopia and related ocular traits like axial length. Multi-cohort meta-analyses, which integrate data from participants across various geographic regions including the United States, Europe, Australia, and Asia, have provided robust evidence for the replication of numerous genetic loci influencing both myopia and hyperopia[4]. These studies typically involve thousands of individuals, providing substantial statistical power to detect genetic associations and contributing to the generalizability of findings across diverse populations, while also assessing for potential heterogeneity across the included cohorts [1].
Methodologically, these population studies rely on extensive sample sizes and rigorous study designs to investigate complex genetic and environmental interactions. Foundational cohort studies, such as the Copenhagen City Eye Study which included 9980 Scandinavian adults [18], and the Rotterdam Study providing age-specific prevalence data in an older population [19], exemplify the scale and depth of research in this field. Meta-analyses, which synthesize data from multiple individual studies, further enhance the reliability and representativeness of findings by pooling statistical power and accounting for variations across different research settings. Such large-scale epidemiological efforts are critical for advancing the understanding of genetic associations and the broader population-level dynamics of myopia.
Frequently Asked Questions About Myopia
Section titled “Frequently Asked Questions About Myopia”These questions address the most important and specific aspects of myopia based on current genetic research.
1. My parents are nearsighted; will I be too?
Section titled “1. My parents are nearsighted; will I be too?”Yes, there’s a strong chance. Myopia has a high heritability, meaning it often runs in families, with genetic factors contributing significantly to its development. Twin studies show that refractive error and axial length can be up to 90% heritable. So, your family history is a significant indicator of your own risk.
2. Why do I need glasses but my friends don’t?
Section titled “2. Why do I need glasses but my friends don’t?”Your eyesight is likely influenced by a unique combination of your genes and daily habits. While environmental factors like extensive near work play a role, genetic predispositions are significant. Researchers have identified many specific genetic regions and variants linked to myopia, meaning some people are simply more genetically prone to developing it than others.
3. Does reading books all day make my eyes worse?
Section titled “3. Does reading books all day make my eyes worse?”Yes, it can contribute. Extensive near work, like reading for long periods, is identified as an environmental factor that influences the development of myopia. While genetics play a big role, your daily habits can definitely impact how your eyesight develops and progresses.
4. Is it true Asian people get more nearsighted?
Section titled “4. Is it true Asian people get more nearsighted?”Yes, that’s true. The prevalence of myopia is indeed notably higher in Asian populations compared to other global regions. This observation has led to many genetic studies focusing on these specific groups, identifying variants that may be more common or impactful in certain ancestries.
5. Can I prevent my kids from getting really bad eyes?
Section titled “5. Can I prevent my kids from getting really bad eyes?”Understanding the genetic factors is key for future prevention. While myopia has strong genetic links, researchers are actively working to identify the specific genetic determinants. This knowledge is crucial for developing more effective prevention strategies and treatments in the future to help mitigate the risk of severe myopia in children.
6. My eyes are really bad; am I at higher risk for problems?
Section titled “6. My eyes are really bad; am I at higher risk for problems?”Yes, having high myopia significantly increases your risk for other eye problems. If your spherical equivalent refraction is below -6.00 diopters, you’re considered to have high myopia, which is linked to a very elongated eye. This condition can lead to various visual morbidities and, in its pathological form, is a leading cause of irreversible visual impairment.
7. Does studying a lot in college make my eyesight worse?
Section titled “7. Does studying a lot in college make my eyesight worse?”It can be a contributing factor. Higher education, often associated with extensive near work and prolonged focus on close objects, is recognized as an environmental factor influencing myopia development. So, while studying is important, it can place demands on your eyes that contribute to changes in vision.
8. Why do some people never need glasses, even if they read?
Section titled “8. Why do some people never need glasses, even if they read?”It comes down to their genetic makeup. While extensive reading is an environmental factor, some individuals have genetic predispositions that protect them from myopia. Their genetic variants might make them less susceptible to the eye changes, like axial elongation, that cause nearsightedness, even with similar environmental exposures.
9. Is my “bad” eyesight just bad luck, or more complex?
Section titled “9. Is my “bad” eyesight just bad luck, or more complex?”Your eyesight is a result of a complex interplay, not just bad luck. Myopia development is influenced by both your genetic predispositions and environmental factors, such as how much near work you do. It’s a combination of these elements that determines your individual risk and the severity of your myopia.
10. Can I overcome my family’s weak eyesight with good habits?
Section titled “10. Can I overcome my family’s weak eyesight with good habits?”While good habits are beneficial, genetics play a very strong role, especially for severe forms. Myopia is significantly influenced by genetic predispositions, with high heritability. Environmental factors like near work also contribute, so good habits can help, but they might not fully counteract a strong genetic tendency, particularly for high or pathological myopia.
This FAQ was automatically generated based on current genetic research and may be updated as new information becomes available.
Disclaimer: This information is for educational purposes only and should not be used as a substitute for professional medical advice. Always consult with a healthcare provider for personalized medical guidance.
References
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