Myopia
Myopia, commonly known as nearsightedness, is a refractive error characterized by the inability to see distant objects clearly while near vision remains intact, resulting from excessive axial length of the eyeball or excessive curvature of the cornea or lens, which causes light rays to focus in front of the retina rather than on it.[1][2][3] Affecting approximately 30-37% of the global population as of recent estimates, myopia prevalence varies significantly by region, with rates exceeding 60% in parts of East Asia among young adults compared to around 23-40% in Europe, and is projected to reach 50% worldwide by 2050 due to urbanization, increased near work, and reduced outdoor time.[4][5][6] Empirical evidence indicates that while genetic factors contribute to susceptibility, environmental influences—particularly prolonged near-focus activities like reading or screen use and insufficient exposure to natural light—drive the axial elongation underlying myopia progression, as demonstrated in longitudinal studies and animal models of visual deprivation.[7][8][9] High myopia, defined as greater than -6 diopters, elevates risks for complications such as retinal detachment, myopic macular degeneration, and glaucoma, underscoring the public health implications of its epidemic rise, though correction via spectacles, contact lenses, or refractive surgery effectively manages symptoms in most cases.[10][3]Clinical Presentation
Signs and Symptoms
Myopia, or nearsightedness, is characterized by difficulty seeing distant objects clearly while near vision remains intact.[11][12] This refractive error results in images focusing in front of the retina, leading to blurred distance vision.[7] Common symptoms include eye strain, headaches, and squinting to sharpen focus on faraway targets.[13][12] Patients may report fatigue after tasks requiring prolonged distance viewing, such as driving or watching television.[7] In children, subtle behavioral indicators often precede formal diagnosis, such as holding books or screens excessively close to the face or complaints about not seeing classroom blackboards or sports details from afar.[14][15] These signs reflect compensatory habits to overcome visual deficits.[7] High myopia, defined as greater than -6 diopters, may present with additional risks like floaters from vitreous changes or early cataracts, though the primary symptom remains uncorrected distance blur.[7][16] Nocturnal myopia can cause exacerbated blur in low-light conditions due to shifts in accommodation.[17] Without correction, chronic symptoms can impair daily activities and quality of life.[12]Classification by Type and Severity
Myopia is classified into several types based on anatomical, etiological, and clinical features. Anatomically, it is categorized by the primary optical mechanism causing the refractive error: axial myopia, resulting from excessive elongation of the eye's axial length (with each 1 mm increase typically producing a 3 diopter myopic shift); curvature myopia, due to excessive corneal or lenticular curvature; and index myopia, arising from alterations in the refractive index of the ocular media, such as in diabetes or nuclear cataracts (though rare).[7][18] Etiologically, myopia includes simple or physiologic forms, which are non-pathologic and often school-age onset without structural damage; pathologic or degenerative myopia, characterized by high refractive errors (typically > -6 diopters) accompanied by posterior staphyloma, lacquer cracks, or myopic maculopathy leading to potential vision loss; and secondary or induced types, such as those from drugs (e.g., sulfonamides), accommodative spasm, or postoperative changes.[17][18] Transient variants, including pseudomyopia from ciliary muscle spasm or nocturnal myopia in low light, are temporary and reversible upon addressing the trigger.[17] Severity is primarily graded by the spherical equivalent refractive error under cycloplegia to minimize accommodation effects. The International Myopia Institute proposes standardized thresholds: myopia as ≤ -0.50 diopters (D), low myopia as > -6.00 D to ≤ -0.50 D, and high myopia as ≤ -6.00 D, with pathologic myopia distinguished not solely by degree but by structural ocular changes conferring risks like retinal detachment.[18] Alternative clinical categorizations include mild (-0.50 D to -4.00 D), moderate (-4.00 D to -8.00 D), and severe (> -8.00 D), though thresholds vary across guidelines, with high myopia often starting at > -6.00 D and associated with elevated complication risks.[7][17]| Severity Category | Diopter Range (Spherical Equivalent) | Key Characteristics |
|---|---|---|
| Low/Mild | ≤ -0.50 D to > -6.00 D | Generally physiologic; low risk of pathology; correctable with standard optics.[18][17] |
| High/Severe | ≤ -6.00 D | Increased axial length; higher incidence of complications like choroidal neovascularization.[7][18] |
| Pathologic | Often > -8.00 D with structural changes | Degenerative retinal/choroidal alterations; requires monitoring beyond refraction.[7] |
Pathogenesis
Ocular Mechanisms
Myopia arises primarily from axial elongation of the eyeball, which shifts the retinal plane posterior to the focal point of incoming light rays, resulting in blurred distance vision. This elongation disrupts emmetropization, the developmental process that normally calibrates ocular growth to achieve refractive neutrality. In emmetropic eyes, axial length approximates 23-24 mm in adults, but myopic eyes exceed this, with each millimeter increase corresponding to roughly 3 diopters of myopia.[19][20] The sclera plays a central role in accommodating this elongation through biomechanical remodeling, transitioning from a rigid structure to one capable of expansion. During myopia progression, scleral thickness decreases, particularly posteriorly, while extracellular matrix (ECM) components like collagen fibrils exhibit reduced diameter and packing density, diminishing tensile strength. This is accompanied by upregulated matrix metalloproteinases (MMP-2 and MMP-3) and decreased tissue inhibitors of metalloproteinases (TIMPs), yielding net ECM degradation and scleral thinning.[21][22] Proteoglycan alterations, including reduced lumican and biglycan, further weaken the scleral matrix, facilitating passive distension under intraocular pressure.[21] Retinal and choroidal tissues contribute via growth-regulating signals in response to optical defocus. Hyperopic defocus—where the image plane falls behind the retina—triggers local retinal pathways that promote elongation, potentially through dopamine and glucagon signaling deficits. The choroid thins rapidly in early myopia, reflecting vascular and stromal changes that may modulate scleral perfusion and metabolite delivery. Retinal pigment epithelium (RPE) ion transport and growth factor release, such as those involving vascular endothelial growth factor (VEGF), influence adjacent choroidal and scleral remodeling.[23][24] Corneal and lenticular changes are minor contributors, with corneal power typically flattening slightly (0.2-0.5 diopters) in myopes, insufficient to explain refractive shifts. In high myopia, the globe assumes a prolate ellipsoid shape, stretching photoreceptor arrays and thinning the retina, which elevates risks for complications like macular degeneration. Axial elongation persists into adulthood in high myopes at rates of about 0.03 mm/year, decelerating with age and baseline length.[25][26]Genetic Factors
Heritability estimates for myopia, derived from twin and family studies, indicate a substantial genetic component, with narrow-sense heritability ranging from 0.60 to 0.94 for refractive error and axial length in various populations.[27] Monozygotic twins exhibit concordance rates for myopia significantly higher than dizygotic twins, supporting additive genetic influences over shared environment alone.[28] These studies consistently demonstrate that genetic factors account for 70-90% of variance in myopia susceptibility, particularly in low to moderate cases, though estimates vary by age, ethnicity, and myopia severity.[29] Genome-wide association studies (GWAS) have identified over 500 common genetic variants associated with refractive error and myopia, primarily through large-scale meta-analyses involving hundreds of thousands of participants.[30] These loci, often near genes involved in eye development, scleral remodeling, and neuronal signaling (e.g., those regulating extracellular matrix or dopamine pathways), each confer small effect sizes but collectively explain up to 15-20% of phenotypic variance.[31] High myopia shows enrichment for rare variants, with exome sequencing revealing pathogenic mutations in genes like those implicated in syndromic forms (e.g., collagen-related genes), contributing to severe axial elongation.[32] Polygenic risk scores (PRS), aggregating effects from GWAS-derived variants, predict myopia onset and progression with moderate accuracy, achieving area under the receiver operating characteristic curve (AUROC) values of 0.65-0.70 in independent cohorts.[33] Recent PRS models, refined for specific ancestries such as East Asian populations, enhance detection of high myopia risk in children, though predictive power remains limited without integration of non-genetic factors.[34] Overall, myopia's genetic architecture reflects a polygenic threshold model, where cumulative liability from common and rare variants predisposes individuals, underscoring the absence of single-gene determinism except in rare familial cases.[35]Environmental Factors
Increased time spent on near work activities, such as reading or using digital screens, is associated with higher odds of myopia development and progression, with meta-analyses reporting an odds ratio of 1.14 (95% CI: 1.08-1.20) for additional near work time.[36] This association holds across cohort and cross-sectional studies, though causation remains debated due to potential confounding by factors like education intensity.[37] Prolonged near work may induce accommodative stress or alter retinal signaling, contributing to axial elongation of the eye.[38] Greater time outdoors, particularly exposure to natural sunlight, consistently shows a protective effect against myopia onset, with multiple reviews finding reduced incidence and slower progression in children spending more than 2 hours daily outside.[39] For instance, interventions increasing outdoor time by 1-2 hours per day lowered myopia risk by up to 50% in randomized trials, independent of ethnicity or baseline refractive error.[40] The mechanism likely involves higher-intensity light stimulating retinal dopamine release, which inhibits scleral remodeling and axial growth.[41] Even short bursts of sunlight exposure (at least 15 minutes) correlate with less myopic shift, as measured by wearable devices.[42] Higher educational attainment and intensive schooling environments correlate strongly with elevated myopia prevalence, with studies showing odds ratios up to 2-3 times higher in populations with prolonged indoor academic demands.[43] This link persists after adjusting for genetics, as evidenced by birth month analyses where later school entry reduces myopia risk due to more pre-school outdoor exposure.[44] Urbanization amplifies these effects through reduced green space access and increased near work, with rural-urban prevalence gaps exceeding 20% in multiple cohorts.[45] Digital screen time, a modern near work variant, shows dose-dependent risks, though evidence is stronger for total near work duration than device type alone.[46]Gene-Environment Interactions and Debates
Twin and family studies consistently demonstrate high heritability for myopia, with estimates ranging from 0.60 to 0.90, indicating that genetic factors account for a substantial portion of refractive error variation within populations.[47] However, the explosive rise in myopia prevalence—such as from approximately 10-20% in European cohorts born in the 1950s to over 50% in those born after 1990—occurs too rapidly to be attributable to shifts in gene frequencies, underscoring the necessity of environmental modifiers acting on genetic predispositions.[45] Polygenic risk scores derived from genome-wide association studies (GWAS), encompassing over 450 loci associated with myopia, interact with environmental exposures; for instance, individuals with elevated genetic risk show amplified refractive progression when exposed to high levels of near work or education, as evidenced by longitudinal cohort data.[48][49] These interactions likely operate through pathways where genetic variants influence scleral remodeling or retinal signaling, modulated by environmental cues like reduced natural light exposure, which may suppress dopamine release and alter emmetropization. Mendelian randomization analyses, leveraging genetic variants as instrumental variables, provide causal evidence that prolonged education—a proxy for intensive near work—elevates myopia risk independently of confounding socioeconomic factors.[35] Conversely, outdoor time exerts a protective effect, with randomized trials showing 2-3 hours daily reducing incidence by up to 50% in high-risk groups, suggesting gene-dependent responsiveness to light-mediated mechanisms.[35] Debates center on the relative primacy of genetic versus environmental drivers: proponents of a predominantly genetic etiology argue that heritability metrics and stable familial patterns indicate environment primarily accelerates progression in genetically susceptible individuals, rather than initiating de novo cases.[50] Critics counter that population-level epidemics, particularly in urbanizing East Asia where prevalence exceeds 80% among young adults, reflect causal environmental dominance, as genetic evolution cannot account for decadal surges; this view is bolstered by animal models demonstrating environmentally induced axial elongation absent in controls.[51][52] Resolution remains elusive, with calls for larger-scale interaction studies using polygenic scores and environmental tracking to disentangle effects, though methodological challenges like unmeasured confounders persist.[35] Emerging evidence from multi-ancestry GWAS hints at ancestry-specific interactions, where East Asian genomes may confer heightened vulnerability to modern visual demands.[49]Epidemiology
Global Prevalence and Projections
The global prevalence of myopia across all age groups was estimated at 22.9% (1.4 billion people) in 2000, rising to approximately 30% (around 2.6 billion people) by the early 2020s, reflecting a sustained upward trend driven primarily by increases among younger populations.[53][6] Among children and adolescents specifically, meta-analyses of studies spanning 1990 to 2023 report a pooled prevalence escalating from 24.3% to 35.8%, with current estimates around 30.5% globally.[4][54] These figures derive from systematic reviews aggregating cycloplegic refraction data across diverse populations, though variations exist due to differences in diagnostic criteria and underreporting in low-resource regions.[4] Projections to 2050, modeled on age-, gender-, and ethnicity-stratified trends from 1990 onward, forecast that myopia will affect nearly 50% of the world's population (approximately 4.8 to 5 billion individuals), representing a roughly twofold increase from early 21st-century levels.[53][55] High myopia (typically defined as ≤ -6 diopters) is anticipated to reach 10% prevalence globally, heightening risks of associated complications like retinal detachment.[53] For children and adolescents, prevalence could exceed 39-40% by mid-century, potentially impacting over 740 million individuals in that demographic alone, assuming continuation of current urbanization and lifestyle patterns without widespread interventions.[56][57] These estimates, from meta-regression analyses, carry uncertainties related to demographic shifts and potential mitigation efforts, such as increased outdoor activity, but underscore the trajectory toward a public health challenge of unprecedented scale.[53][4]Regional and Demographic Variations
Myopia prevalence varies markedly by region, with East and Southeast Asia exhibiting the highest rates globally. In urban East Asian populations, myopia affects over 80% of young adults, driven by high incidence in school-aged children.[58] In contrast, rates in Europe are substantially lower, with a meta-analysis reporting childhood and adolescent prevalence ranging from 11.9% in Finland to 49.7% in Sweden, influenced by age and national differences.[59] In the United States and Europe, adult myopia prevalence hovers around 30-33%, far below East Asian figures.[60] Regions like sub-Saharan Africa and the Eastern Mediterranean show even lower childhood rates, with pooled prevalence of 5.23% in the latter from 2000-2022 studies.[61] Demographic factors further delineate variations. Ethnically, East Asians consistently demonstrate the highest myopia rates, exceeding those of white Europeans by more than twofold in comparable age groups; South Asian children face a ninefold risk relative to white Europeans, while black African Caribbeans experience a threefold increase.[62][63] Gender disparities appear in several contexts, with females showing higher prevalence than males, such as 4.90% versus 3.94% in Eastern Mediterranean schoolchildren.[61] Age-related patterns reveal escalating prevalence through childhood and adolescence, from under 3% in ages 0-4 to over 67% in late teens in aggregated global data, stabilizing in adulthood.[64]| Ethnicity (Children) | Myopia Risk Relative to White Europeans | Source |
|---|---|---|
| East Asian | >2-fold | [63] |
| South Asian | 9-fold | [62] |
| Black African Caribbean | 3-fold | [62] |