Pathogenesis of Glaucoma via Lamina Cribrosa Damage

The lamina cribrosa is a sieve-like structure in the posterior sclera where retinal ganglion cell (RGC) axons and central retinal vessels exit the eye. It is supported by connective tissue beams and has pores through which axons and blood vessels supplying the optic nerve head pass. This preserves a pressure gradient between the intraocular and extraocular space.

Raised intraocular pressure (IOP)

• Elevated IOP → mechanical stress on the optic nerve head.
• The lamina cribrosa is particularly vulnerable because it is the transition point between intraocular pressure and the lower-pressure retrobulbar space.
• Chronic high IOP causes posterior bowing and distortion of the lamina cribrosa.

Mechanical injury to axons

• Bowing narrows the pores in the lamina cribrosa → compression and distortion of the RGC axons.
• This disrupts:
  • Axoplasmic transport (movement of nutrients and signalling molecules along the axon).
  • Mitochondrial transport, leading to local energy deficits.
• Transport blockage occurs both anterogradely (toward the brain) and retrogradely (from the brain toward the RGC soma).

Vascular compromise

• Compression of laminar capillaries reduces blood flow to the optic nerve head.
• Local ischemia leads to hypoxia and increased oxidative stress in axons and glial cells.

Biochemical cascade

• Axonal injury → accumulation of neurotoxic proteins and impaired neurotrophic factor delivery (e.g., BDNF) to RGC bodies.
• Microglia and astrocytes in the optic nerve head become activated, releasing:
  • Inflammatory cytokines (TNF-α, IL-1β)
  • Reactive oxygen species
  • Glutamate (excitotoxicity).

Retinal ganglion cell death

• Deprived of neurotrophic support and under oxidative/metabolic stress, RGCs undergo apoptosis.
• The death is progressive and irreversible, explaining the chronic, insidious nature of glaucoma.
• Loss of RGC axons → optic nerve cupping due to tissue loss at the optic disc.
• Corresponding visual field defects begin in the periphery and advance toward central vision.

Corneal thickness as a biomechanical clue

• Central corneal thickness (CCT) is often used as a surrogate for the overall stiffness and connective tissue properties of the eye.
• Both the cornea and the lamina cribrosa are largely made of collagen-rich extracellular matrix.
• If your cornea is thin, it may indicate that the lamina cribrosa is also more compliant (less rigid) and therefore more prone to deformation under the same intraocular pressure (IOP).

• Thin cornea → lamina cribrosa likely to be structurally weaker.
• Under raised or even “normal” IOP:
  • Lamina cribrosa bows posteriorly more easily.
  • This increases axonal compression and pore distortion, accelerating the pathogenic sequence we discussed earlier.
• This helps explain why thin CCT is a strong risk factor for glaucoma progression (especially in normal-tension glaucoma).

• In tonometry:
  • Thin corneas tend to give underestimated IOP readings.
  • This means a patient might appear to have “normal” pressure, but the lamina cribrosa is still being stressed.
• This can delay diagnosis unless corneal thickness is measured and interpreted alongside optic nerve head assessment.

Thin cornea = softer lamina cribrosa = more optic nerve head deformation under IOP = higher glaucoma risk.