What is the pathophysiology of posterior subcapsular cataract?

Pathophysiology of Posterior Subcapsular Cataract

Posterior subcapsular cataracts (PSCs) develop through a two-stage process involving oxidative stress, lens epithelial cell migration, and inflammation that leads to characteristic opacification at the posterior pole of the lens. 1

Types and Morphology

Two distinct types of posterior subcapsular cataracts have been identified:

1. Vacuolar-lacy type:

   • More superficial (closer to posterior capsule)
   • Characterized by cellular proliferation
   • Seen in senile, diabetic, retinitis pigmentosa, steroid-induced, and secondary cataracts
   • Contains aberrantly migrated lens epithelial cells
   • These cells secrete basement membrane, filaments, and release cytolytic lysozymes

2. Solid plaque type:

   • Located slightly deeper in the cortical region
   • Acellular in nature
   • Observed in congenital polar cataracts, myotonic dystrophy, and Turner syndrome
   • Shows breakdown of lens fibers into disorganized globules and membranous whorls 2

Two-Stage Pathophysiological Process

Stage I (Early Development)

• Triggered by risk factors promoting oxidative stress and ion-pump disruption
• Damages lens fibers
• Causes aberrant lens epithelial cells (LECs) to proliferate
• LECs migrate ectopically as Wedl cells to the posterior pole region
• May involve epithelial-to-mesenchymal transition (EMT) 1

Stage II (Progression)

• Follows a latent period
• Characterized by chronic inflammation
• Premature aging-related mechanisms advance
• Results in mature vacuolar or plaque PSC formation 1

Key Molecular and Cellular Mechanisms

• Lens epithelial cell dysfunction: LECs are normally hypoxic and highly sensitive to oxidative stress 1
• Epithelial-mesenchymal transition: LECs transform into myofibroblast-like cells 3
• Aberrant migration: LECs migrate posteriorly instead of equatorially 2
• Protein expression changes:
  • Decreased expression of ephrin type-A receptor 2 (EphA2)
  • Increased expression of α-smooth muscle actin (α-SMA)
  • Altered expression of αB-crystallin (CRYAB) and heat shock protein beta-1 (HSPB1) 4
• Extracellular matrix deposition: Collagen accumulation and basement membrane secretion 3, 2
• Cellular proliferation: Unregulated growth of lens epithelial cells 3
• Lens fiber generation: Abnormal lens fiber formation 3

Risk Factors Contributing to PSC Development

Several factors can initiate the pathophysiological cascade:

• Aging: Natural degenerative processes
• Diabetes: Metabolic disruption and oxidative stress
• Steroid use: Alters lens epithelial cell function and migration
• Ionizing radiation: Directly damages LECs and increases oxidative stress
• UV-B exposure: Associated with increased risk of PSC formation 5
• Ocular conditions: Retinitis pigmentosa, uveitis, vitrectomy
• Systemic conditions: Hypoparathyroidism, myopia, atopy
• Solar radiation: Contributes to oxidative damage 1, 5

Clinical Implications

• The vacuolar type is more readily removed during extracapsular cataract extraction
• Retention of nucleated lens epithelial cells in vacuolar opacities can lead to secondary cataracts (Hirchberg-Elschnig pearls)
• Secondary cataracts may require additional procedures to clear the visual axis 2
• Posterior capsular opacification (PCO) remains a common complication after cataract surgery, requiring Nd:YAG laser capsulotomy 3

Prevention Considerations

• Potential for reducing PSC incidence by targeting Stage I mechanisms
• Ocular antioxidants may help counteract oxidative stress
• Improvements in surgical techniques, intraocular lens materials, and designs have reduced PCO rates 1, 3