The pathogenesis of primary open angle glaucoma Flashcards
what is the definition of glaucoma
a progressive optic neuropathy having characteristic morphological changes of the optic nerve head and retinal nerve fibre layer
in the absence of other ocular disease and their congenital abnormalities
what 2 components does glaucoma cause damage to and what does this damage result in
- the optic nerve head
- the peripapillary retinal nerve fibre layer
results in a characteristic visual field defect
how common is glaucoma as a cause of blindness in the UK
2nd/3rd most common cause
__________ registration from glaucoma continues to ________
blindess registration from glaucoma continues to increase
what are the 2 classifications of glaucoma
- primary glaucoma
- secondary glaucoma
what are the 2 types of primary glaucoma
- open angle
- closed angle
what is secondary glaucoma the result of
due to underlying medical condition or injury to the eye
how much of all glaucomas encountered does POAG account for
the majority - 85%
what is POAG due to
the resistance in the aqueous outflow pathway
what are the 2 routes which aqueous leaves the eye
- trabecular meshwork
- uveoscleral outflow
list the steps of production of aqueous to when in reaches the anterior chamber
- aqueous humour is produced by the ciliary epithelium
- it percolates out into the posterior chamber
- it passes through the pupil
- and into the anterior chamber, where it circulates
what is the role of aqueous humour
to provide nutrients to the lens and cornea (particularly the corneal endothelium) and to remove metabolic waste product from these 2 areas
what are the 2 classes of outflow pathways of aqueous humour
- conventional - trabecular meshwork
- unconventional - eveoscleral
explain how aqueous drains from the eye via the conventional pathway
aqueous leaves through the trabecular meshwork into schlemm’s canal and then into collector channels and episcleral veins
explain how aqueous drains from the eye via the unconventional pathway
aqueous passes through interstitial spaces of ciliary muscle and choroid, or suprachoroidal space transclerally
majority ____% of aqueous will leave through the ___________ ____________
majority ~90% of aqueous will leave through the trabecular meshwork
what is the trabecular meshwork composed of
primarily of collagen beams which interlace with each other
how is the trabecular meshwork constructed and why
the collagen beams leaves spaces/pores at which the aqueous passes
how many anatomical regions are there of the trabecular meshwork and describe each one
1st region: uveal meshwork - here the spaces between the trabecular beams/pores are quite large, therefore when aqueous passes through here, theres very little resistance to its flow
2nd region: corneoscleral meshwork - here the pore sizes/spaces formed by the beams are much smaller, therefore causes a slightly more resistance to flow of aqueous to this region
3rd region: juxtacanalicular meshwork - which lines schlemm’s canal, at this point this is where aqueous is at its most resistance
aqueous collects into schlemm’s canal through the formation of giant vacuoles, the aqueous then goes through the collector channels and drains into the epi scleral veins
what is the 1st region of the trabecular meshwork called and what happens with the aqueous here
uveal meshwork
here the spaces between the trabecular beams/pores are quite large, therefore when aqueous passes through here, theres very little resistance to its flow
what is the 2nd region of the trabecular meshwork called and what happens with the aqueous here
corneoscleral meshwork
here the pore sizes/spaces formed by the beams are much smaller, therefore causes a slightly more resistance to flow of aqueous to this region
what is the 3rd region of the trabecular meshwork called and what happens with the aqueous here
juxtacanalicular meshwork
which lines schlemm’s canal, at this point this is where aqueous is at its most resistance
how does the aqueous drain away once it has reached schlemm’s canal
aqueous collects into schlemm’s canal through the formation of giant vacuoles, the aqueous then goes through the collector channels and drains into the epi scleral veins
list the stages of where the aqueous drains through via the unconventional pathway
- the aqueous bypasses the trabecular meshwork
- there is no epithelial barrier between the anterior chamber and supraciliary space
- so the aqueous collects into this space
- it then goes through into the inter muscular spaces of the ciliary body which is filled with lose connective tissue
- then it goes through the suprachoroidal space which also has lose connective tissue and is considered largely as a potential space
- the aqueous they gradually diffuses through the M scleral channels of the sclera
what is the supraciliary space
its space just above the ciliary body
what is the inter muscular spaces of the ciliary body
it is space between the 3 layers of the ciliary muscle which is filled with lose connective tissue and some ground substance which makes it potential for aqueous to collect there
what is the suprachoroidal space
space just above the choroid, also another space for aqueous to collect
what happens to the aqueous in glaucoma that results in a patient having increased IOP
- aqueous is produced as normal
- there is increased resistance to drainage
what 2 factors can cause an increased resistance to drainage
- increases with age - due to hardening of the trabecular meshwork
- genetic factors - affect the composition of the collagen beams of the trabecular meshwork, may predispose px from getting glaucoma
in open angle glaucoma, the build up of ______ __________ in the anterior chamber has the effect of building up the _________ ____________ in the eye that causes damage to the _______ ________ and ____________________ and this damage in the _____ will manifest as a ________ _________ _________
in open angle glaucoma, the build up of fluid pressure in the anterior chamber has the effect of building up the overall pressure in the eye that causes damage to the optic nerve and retinal nerve fibre layer and this damage in the NFL will manifest as a visual field defect
damage to the _________ ONH and RNFL manifests as a __________ ___________ visual field defect
damage to the inferior ONH and RNFL manifests as a superior paracentral visual field defect
where is the primary sight of insult from raised IOP
optic nerve head
what structure does the damage of the ONH subsequently damage
retinal ganglion axons - irreversible permanent damage
what is the environment of the retina important for
helping the RGCs stay viable and healthy with its support cells
what support cells does the retina have in order to keep RGCs healthy and how do they support provide this support
- muller cells
- amacrine cells
- astrocytes
they all provide nutrition and help to maintain glutamate homeostasis in the retina
why is glutamate needed in the retina
to ensure that nerve cells will fire
glutamate homeostasis has recently been shown to play a role in RGC viability
what are the 2 features that contribute to the glaucomatous optic neuropathy
- microcirculation - which provides nutrition and removes waste products of the ONH and retrobulbar ON
- the lamina cribrosa/ONH itself - how the axons pass through here
these two features can potentially contribute to causing damage to the RGC axons and causing glaucoma
what are the 2 theories of glaucoma
- mechanical theory
- vascular theory
what is the lamina cribrosa and what exits the eye via this structure
- a series of perforated collagenous sheets, like a sieve
- retinal ganglion cell axonal bundles which leave the eye from the ONH, have to go through the lamina cribrosa before they get to the bulbar optic nerve
how is the lamina cribrosa structures in humans
the pore sizes are varied by region, with the inferior and superior poles have pores which are much larger, so larger bundles go through these pores, compared to those passing through the nasal and temporal poles
how are the path of the RGC axons when they go through the sieve of the lamina cribrosa
the path of the axons are not straight as each axon bundle has to go a convoluted way through the lamina cribrosa before it reached the retro bulbar space
how does raised IOP have a direct effect on the lamina cribrosa
which forms the basis of the mechanical theory of glaucoma damage
it causes compression of the lamina cribrosa plates and a shearing/stretching of the pores, so as the bundles pass through the pores, they get damaged (i.e. stretched, sheared and compressed)
this forms the basis of the mechanical theory of glaucoma damage
what happens to the RNFL as the axon bundles get damaged
the axon bundles start to die off and in the RNFL they start to coalesce to form larger wedge defects if they pressure remains uncontrolled and the lamina remains damaged
this regional pore size helps to explain why in glaucoma, you have damage to the inferior and superior RNFL first, because the pores in these areas are larger so theres more axon bundles going through these areas hence causing more stretching, shearing and damage
what is the appearance of the ONH like as a result of glaucoma and the associated structures
- the lamina cribrosa which is in the optic cup have slightly striated and distorted pores
- there can be a notch = a complete loss of the inferior NRR
- the calibre of the blood vessel is going to go into the exasperated cup and coming out again in the inferior retinal surface
what does the vascular theory of glaucoma describe
how the microcirculation changes and how this will contribute to RGC damage and RGC axon damage
if the blood vessels supplying the RGC axons are poorly perfused/theres not enough blood passing through these blood vessels, then that axon bundle will not get nutrition or removal of waste therefore the axon bundle gradually gets damaged and will die
what is the appearance of a healthy ONH and retro bulbar ON
they are well perfused = have millions of micro capillaries that will supply nutrients to the optic nerve and RGC axons as they leave the retina and pass through the ONH
there is no direct contact between the _________ _________ and __________ __________ as each axon bundle is protected by a layer of __________, but each bundle has its own ________ _________
there is no direct contact between the blood vessels and axonal bundles as each axon bundle is protected by a layer of astrocytes, but each bundle has its own vascular supply
list 3 causes of potential mechanisms of poor ocular blood flow/perfusion
- local resistance to ocular blood flow
- reduced ocular perfusion pressure
- blood hyper viscosity
what 2 things can cause local resistance to ocular blood flow
- atherosclerosis - at the level of the ONH or bulbar ON which can be caused by systemic diseases
- defective auto regulation - instead of bv’s dilating, they constrict
what 3 things causes reduced ocular perfusion pressure
- increase in IOP or decrease in BP or both
- microvascular disease, peripheral vasospasm (Raynaud’s, migraine), systemic hypotension
has a direct affect on the calibre of the blood vessels = almost like a compression of those capillaries therefore not enough nutrition is getting to the optic nerve. so raised IOP has a direct affect on ocular blood flow
