What is the pathophysiology of myopia?

Pathophysiology of Myopia

Myopia primarily develops due to excessive axial elongation of the eyeball, resulting from complex gene-environment interactions that disrupt normal eye growth regulation. 1, 2

Anatomical Changes

• Axial elongation: The fundamental anatomical change in myopia is an increase in the axial length of the eyeball, causing light to focus in front of the retina rather than directly on it 3
• This elongation affects primarily the vitreous chamber depth
• Structural changes also occur in the sclera, choroid, and retina as the eye elongates

Etiology: Gene-Environment Interaction

Genetic Factors

• More than 450 common genetic loci have been associated with myopia development 1
• Higher prevalence in individuals with myopic parents, strongly suggesting genetic predisposition 3
• Genetic factors influence:
  • Scleral composition and biomechanics
  • Eye growth regulation pathways
  • Susceptibility to environmental triggers

Environmental Factors

• Near work activities: Extended reading, screen time, and close-up tasks 1
• Reduced outdoor time: Decreased exposure to natural light 4
• Educational intensity: Higher levels of education correlate with increased myopia prevalence 1
• Urban living environments with limited distance viewing opportunities

Pathophysiological Mechanisms

1. Defocus-Driven Eye Growth

   • Hyperopic defocus (image focused behind the retina) triggers compensatory eye elongation
   • Peripheral retinal defocus may stimulate axial elongation even when central vision is clear

2. Biochemical Pathways

   • Retinal signals triggered by visual experience affect:
     • Dopamine release (reduced in myopic eyes)
     • Growth factor expression (including VEGF)
     • Inflammatory mediators
   • These signals influence scleral remodeling and eye growth

3. Scleral Remodeling

   • Reduced collagen synthesis
   • Increased matrix metalloproteinase activity
   • Thinning and biomechanical weakening of the sclera
   • These changes facilitate posterior eye elongation

Progression and Complications

• Early onset myopia typically progresses more rapidly 4
• High myopia (≥-6 diopters) affects approximately 20% of myopic individuals 4
• Pathological changes in high myopia include:
  • Retinal detachment
  • Choroidal neovascularization
  • Macular atrophy
  • Early cataract development
  • Increased glaucoma risk 3, 4

Clinical Predictors

• Early hyperopia of ≤0.5 diopters is a predictor of future myopia development 4
• Rapid progression during childhood is associated with higher final myopia
• Family history remains a strong risk factor

Prevention and Control Implications

Understanding this pathophysiology has led to several intervention strategies:

• Increased outdoor activity to increase light exposure and reduce near work time 4
• Optical interventions that manage peripheral defocus (multifocal lenses, orthokeratology) 3, 5
• Pharmacological approaches like low-dose atropine that may influence biochemical pathways involved in eye growth 5

Important Clinical Considerations

• Myopia is not merely a refractive error but should be viewed as a potentially sight-threatening disease requiring early intervention 4
• In children with high myopia, evaluation for syndromic causes is essential 5
• The rapid global increase in prevalence (reaching 80-90% in young East Asian adults) indicates environmental factors are significantly influencing genetic predisposition 4