7. Glaucoma

Question 1

What is glaucoma?

Answer 1

Glaucoma is a blanket term for a variety of conditions that have different features and different mechanims.
The common factor between them is acquired progressive neuropathy. So the optic nerve becomes damaged causing visual field loss and eventual blindness.

Question 2

What are the risk factors of glaucoma?

Answer 2

*Normally asymptomatic.
*High IOP (Over 21mmHg)
*Family history of glaucoma
*Race (Afro Caribbean descent at higher risk)
*Systemic hypertension
*Cardiovascular disease
*Previous ocular disease and use of steroids can increase risk.

Question 3

What are the causes of OAG?

Answer 3

Open angle glaucoma is the only type of glaucoma that is managed using medication.

Primary causes of OAG:
1. High IOP
2. Changes in vasculature - progressive damage to nerve head

Secondary causes of OAG:
1. Pigment dispersion syndrome
2. Lens-induced
3. Post surgery
4. Trauma-induced
5. Intraocular haemorrhage
6. Retinal detachment
7. Uveitis
8. Intraocular tumour
9. Amyloidosis
10. Increased episcleral venous pressure

Question 4

What happens to aqueous humour drainage in glaucoma?

Answer 4

In glaucoma, the balance between production and outflow of aqueous humour is disrupted, and no longer kept at homeostasis. This results in a buildup and increase of intraocular pressure. This pressure buildup is commonly due to dysfunction of the trabecular meshwork, which becomes less efficient at allowing aqueous humour to drain into Schlemm’s canal.

Question 5

What is the IOP circadian rhythm?

Answer 5

Ocular pressure constantly changes over 24 hours. The lowest IOP is at night with the peak IOP being in the morning.
Drainage can also be influenced by postural changes so ocular pressure will be higher after lying down due to increased episcleral venous pressure.

Question 6

What are the drug groups and targets for glaucoma?

Answer 6

It is important to have drugs that are compatible with each other so that they can be used in combination to maximise the effect of the treatment.

1. Prostaglandin and prostamid analogues- increases uveoscleral and trabecular outflow
2. Parasympathomimetics - increases trabecular outflow
3. Beta blockers - Decreases aqueous production
4. Alpha 2 agonists - decreases aqueous production
5. Carbonic anhydrase inhibitors - decreases aqueous production
6. Hyperosmotic agents - increases osmolarity of blood
7. ROCK inhibitors - increases trabecular outflow

Question 7

Describe the mechanism of prostaglandin analogues
and side effects.

Answer 7

PGAs are synthetic analogues of prostaglandin F₂α (PGF₂α).
They bind to FP receptors in the ciliary muscle and uveoscleral tissues.
This leads to:
*Remodelling of the extracellular matrix
*Relaxation of the ciliary muscle
*Widening of spaces in the uveoscleral pathway

These are prodrugs so need to converted (ester to acid) so can bind and activate the FP receptor.
Prodrugs are much more stable so have a longer duration of action, whicih reduces frequency of dosing.

Side effects:
*red eye
*increase pigmentation in iris, eyelashes, and periocular skin
*eyelash growth
*Sensitivity to light
*Precipitate or worsen cystoid macular oedema in aphakic eyes
*Contraindicated in pregnancy

Question 8

Describe the mechanism of action of prostamide analogues and side effects.

Answer 8

Prostamide is produced from a parallel pathway to prostaglandins, from a molecule that is related to arachidonic acid.
Prostamides are analogues of prostaglandins, specifically prostamide F₂α, which is naturally present in the eye. Increase aqueous humour outflow via two pathways:
* Uveoscleral outflow (like prostaglandin analogues)
* Trabecular meshwork outflow
Their dual action helps in more effective IOP reduction.

Same side effects as prostaglandin analogues.

Question 9

Describe the availability of prostaglandin and prostamide analogues.

Answer 9

1. Latanoprost - Multi
2. Travoprost - Multi
3. Tafluprost - Single
4. Bimatoprost - Multi

Question 10

Describe the mechanism of action of beta blockers and side effects.

Answer 10

Beta-blockers are non-selective or selective antagonists of beta-adrenergic receptors in the eye found on blood vessels and ciliary epithelium. They lower intraocular pressure by decreasing aqueous humour production through antagonism of beta-adrenergic receptors in the ciliary epithelium.
Beta 2 receptors are G protein coupled and on activation stimulates cAMP production. Increase cAMP production leads to chloride ion efflux in pigmented epithelial cells. Stimulation of ion transport increases aqueous humour production by osmosis. Beta blockers prevent this, thus decreasing aqueous humour production. Beta 2 receptors on blood vessels can also cause vasodilation so beta blockers prevent this resulting in reducing blood pressure and reducing IOP.

Side effects:
*Cardiovascular - hypotension, bradycardia, peripheral vasoconstriction
*Bronchial - constricts bronchioles, contraindicated in asthma and chronic obstructive airways disease
*Can mask hypoglycemia

Question 11

Describe the availability of Beta blockers

Answer 11

Beta blockers should only be used in the morning when ocular pressure is highest. If used at night can cause cardiac and respiratory problems.

1. Timolol
2. Levobunolol
3. Betoxalol
4. Carteolol