pathogenesis of glaucoma and glaucoma drugs Flashcards
(37 cards)
What is the common feature in glaucoma?
The loss of retinal ganglion cells leading to thinning of retinal nerve fibre layer and cupping of the optic disc
What are the different types of glaucoma?
open angle glaucoma
primary: primary open angle glaucoma, normal tension glaucoma, juvenile glaucoma
secondary: pigment dispersion syndrome, pseudo exfoliation, uveitic
closed angle glacuoma
primary: primary angle closure glacuoma
secondary: rubeitic, uveitic
what are the treatments for open angle glaucoma?
lowering IOP drops
trabecular laser
glaucoma surgery
what are the treatments for closed angle glaucoma?
open drainage pathway
laser periphery iridectomy
lens extraction
lowering IOP drops
glaucoma surgery
what are the risk factors of glaucoma?
raised IOP (greater than 26mmHg)
black ethnicity is a risk factor of open angle glaucoma
angle closure: East Asian, high myopia, DM, FH
what are the clinical features of open angle glaucoma?
Asymptomatic
loss of neural tissue is associated with Suttle changes in NRR (thinning or notching)
Advanced glaucoma: NRR is thin, disc is really cupped, associated with posterior bowing of lamina cribrosa and loss of overlying neural tissue
Retinal ganglion loss is associated with VF defect. Inferior loss. Asymmetric either side of the midline.
Diagnosed based on looking at stereoscopic evaluation of optic nerve head, visual field test, IOP measurement
Further investigation using OCT: can measure thickness of RNFL, monitoring glaucoma
Ocular hypertension associated feature
how can you investigate angle closure glaucoma?
Narrowing or closure of anterior chamber angle best visualised using as gonioscope: contact lens that sits on the surface of the eye. Incorporates a mirror which looks into the angle. Visualisation of TMW.
Van Herricks test.
Pupil block: pupil margin is attached to anterior surface of the lens. iris balloons forward.
Anterior segment oct: can look at anatomical anterior features
what caused increased IOP in OAG and CAG?
OAG: increased IOP due to increased resistance to outflow within TMW
CAG: raised IOP due to pupillary block (attachment between iris periphery and iris TBW narrows angle, you get irido-trabecular contact)
In what 2 ways can IOP impact the pathogenesis of glaucoma?
1.Mechanical (DIRECT): on RNFL and retinal ganglion cells
2.Vascular (INDIRECT): ischaemic mechanism due to reduction in blood flow
where is aqueous produced and drained?
what is level of IOP determined by?
Aqueous is produced by ciliary epithelium (pars plicata)
* From the site of production, the aqueous is secreted into the posterior chamber
* Passes through the pupil where it circulates within anterior chamber
Can leave the eye by 2 mechanisms:
canal of Schlemm is conventional pathway.
Uveoscleral outflow pathway is the other mechanism
- Level of IOP is determined by the balance between rate of aqueous production and rate of drainage
What is the mechanism of aqueous production?how can aqueous secretion be inhibited?
Ciliary epithelium is a double epithelium: pigmented and non-pigmented layer.
These cells work together as a functional unit.
Aqueous production occurs through metabolically driven ion transport systems.
Ions are picked up from stromal side of ciliary epithelium.
Ions are taken up by transport proteins into pigmented epithelium.
Ions Pass via gap junctions into non pigmented epithelium.
Active transport from NPE into posterior chamber
This is a ATP demanding pathway
Carbonic anhydrase is a enzyme that catsylses chemical reaction of carbon dioxide and water to give carbonic acid (important source of bicarbonate ions that play a role in transporter proteins). If you inhibit this enzyme it deprives pathway of a raw material so inhibits aqueous secretion.
what is the outflow pathway for vast majority of aqueous?
what treatments target this pathway?
how much aqueous does uveoscleral pathway drain?
what treatments target this pathway?
TMW-canal of schlemm-intrascleral venous plexus-sclera- episcleral veins onto surface of eye
surgical procedures, laser therapies, few drugs
10-30%. aqueous passes through ciliary body and return into vasculature along posterior segment of eye.
postaglandin analogues
what are the three layers of trabecular meshwork?
what treatments affect trabecular meshwork?
Has 3 distinct layers: uveal trabeculae, corneal scleral trabeculae, and juxta canicular tissue adjacent to canal of Schlemm
* Resistance to outflow is generated in JCT.
drugs which open the pathway or laser therapy to burns hole in meshwork to open spaces to enhance aqueous drainage and lower resistance to outflow.
what surgical mechanisms are there to improve drainage in glaucoma?
Selective laser trabeculoplasty: punching little holes in trabecular meshwork and opening the pathway.
Trabeculectomy: Creating a new aqueous outflow pathway from posterior chamber through to ocular surface
Minimally invasive glaucoma surgery (MIGS): Surgical implants put into the eye (tubes or stents) take aqueous from aqueous humour by passing the resistance.
what are the pharmacological options for regulating IOP?
Inhibit aqueous production: Beta blockers, alpha receptor agonists
Pilocarpine: muscarinic agonist. Opens up TMW.
Most used: prostaglandin agonists. latanoprost. Enhance uveoscleral outflow
how is trabecular meshwork involved in OAG?
OAG is associated with an increased resistance to outflow in the JCT
Thought to relate to changes in extracellular matrix of JCT, slow the rate of aqueous production through layers of meshwork.
Difficult to differentiate between pathological changes and age changes
Plaque like deposits have been described in JCT, specific to glaucoma
how is trabecular meshwork involved in secondary glaucoma?
can arise from intertrabecular spaces being blocked by cellular or non-cellular material. Pigment (pigment dispersion syndrome), inflammatory material (uveitis), pseudo exfoliation glaucoma (material from lens capsule deposits in TMW)
Describe the direct mechanism of optic nerve damage in glaucoma?
*High IOP induces stress at lamina cribrosa (perforated plate made of collagen and glial tissues). Has pores which axons of RGC pass.
*This is vulnerable to raised IOP.
*Lamina cribrosa becomes compressed and deformed.
*This Interrupts axoplasmic flow along axons that pass through it.
* Leads to apoptosis and degeneration of RGC.
*Associated with shrinkage and atrophy of RGC axons.
*We see this at disc as loss of NRR tissue and a posterior extravasion and bowing backwards of lamina cribrosa.
*Axoplasmic flow delivers essential trophic factors to neural cell body. Interfering with this pathway leads to RGC death
Describe the indirect mechanism of optic nerve damage in glaucoma?
*Interruption to blood supply of ONH
*Raised IOP can reduce ocular blood flow.
*This deprives axons of nutrients. Occurs at level of lamina.
*Ischaemic mechanism
*Primary mechanism in those people with normal IOP.
Ischaemia can still occur with normal IOP.
Can be failure of auto regulation.
what are the classes of topical drugs used in glaucoma?
- Prostaglandin agonists/analogues
- Beta receptor antagonists
- Alpha 2 receptor agonists
- Carbonic anhydrase inhibitors
- Cholinergic agonists
what was the first glaucoma drug?
pilocarpine- cholinergic agonist
what should you consider before prescribing any new drop in glaucoma?
*General medical history-need to identify risk of developing adverse reactions
*Drug history-may be interactions with other anti-glaucoma meds
*History of topical allergy
*Find out if px can use eyedrops (memory, dexterity, carers)
what are the mechanism of glaucoma drugs to lower IOP?
reducing aqueous production or act on ciliary epithelium and reduce production of aqueous humour
-increase aqueous outflow through trabecular meshwork
-act on uveoscleral pathway to increase aqueous outflow
when are systemic drugs used in glaucoma?
what are the names of these drugs?
Used to lower IOP in those with acute angle closure glaucoma
- Oral carbonic anhydrase inhibitors e.g., acetazolamide (Diamox)
- Osmotic agents e.g., glycerol, mannitol
