Pathogenesis of Glaucoma Translaminar-pressure difference 부천 성모병원 안과 홍승우

Pathogenesis of Glaucoma Conventional concepts The Mechanical Hypothesis Glaucoma is fundamentally caused by intraocular pressure deforming the optic nerve head and lamina cribrosa The Vascular Hypothesis Elevated intraocular pressure alters the blood flow within the optic-nerve head

Definition of Glaucoma The definition of Glaucoma is any ocular disease that will cause characteristic optic neuropathy or optic nerve damage which may result in progressive visual field loss and it can be associated with either normal or abnormal intraocular pressure. Abnormal intraocular pressure can be high or low

Characteristic optic neuropathy or optic nerve damage Characteristic of glaucomatous field defect Progressive field defect Never cross horizontal merdian Sectoral field defects correspond to RNFL defects * Glaucoma – Optic neuropathy or optic nerve damage occurs within the lamina cribrosa level

Pathogenesis of Glaucoma Conventional concepts The Mechanical Hypothesis It itself can not explain the characteristic glaucomatous damage Focused investigation Structural Properties of Lamina cribrosa The Vascular Hypothesis Except arteritic AION, vascular occlusive diseases which even occurs within the lamina cribrosa do not represent glaucomatous damage - Properties of Microvasculature of Lamina cribrosa

Pathogenesis of Glaucoma Translaminar pressure difference Optic nerve fiber (Retinal ganglion cell) Lies in 2 pressurized compartment Intraocular space and subarachnoid space - Endure pressure gradient Peripheral nerve Can tolerate high pressure up to 3800mmHg However, pressure gradients significantly reduce rapid orthograde axonal transport

Pathogenesis of Glaucoma Translaminar pressure difference Axonal transport Pressure gradient 4.5mmHg/100um (46mmHg/mm) Rapid axonal transport is inhibited

Pathogenesis of Glaucoma Translaminar pressure difference Axonal transport in animal glaucoma model

Pathogenesis of Glaucoma Translaminar pressure difference 11-21mmHg (Sitting position) 5 to 15mmHg (Supine Position)

Pathogenesis of Glaucoma Translaminar pressure difference Translaminar Pressure Gradient (IOP-intracranial pres.) /Depth of Lamina Cribrosa At IOP 15mmHg, ICP 0mmHg, Depth of Lamina Cribrosa 500um = 30mmHg/mm

Pathogenesis of Glaucoma Translaminar pressure difference POAG High IOP, Low CSF pressure NTG Low CSF pressure High glaucoma prevalence in Myopic Pt. Thin Lamina cribrosa OHT High CSF pressure

Translaminar pressure difference Animal Model 1979 Yablonski ME Settings Cats Negative CSF pressure (-4mmHg) One eye – Zero IOP The other eye – no intervention After 3 weeks unchanged eyes developed glaucomatous damage

Cerebrospinal Pressure * In animal model, ON subarachnoid spaces secure their space when CSF pressure drops below zero. CSF Pressure at Brain 0 to -1 mmHg CSF Pressure at Lumbar Puncture site 8 to 15mmHg CSF Pressure at Lower Spine 60 mmHg

Translaminar pressure difference Limitations Normal Tension Glaucoma Normal subarachnoid pressure of optic nerve (0 to -1mmHg) Subarachnoid pressure can be substantially low in NTG patient? NTG patients showed larger subarachnoid space in optic nerve in radiologic studies Glaucoma prevalence in Myopic Pt. Glaucoma prevalence is not so high in myopic Pt. considering lamina cribrosa thickness OHT Subarachoid pressure can be substatially High in OHT patient?

Pathogenesis of Glaucoma Translaminar pressure difference Lamina cribrosa

Pathogenesis of Glaucoma Translaminar pressure difference * Orbital space (Pressure) CSF pressure Intraocular Pressure Pia mata Structures of Subarachnoid space