Glaucoma Flashcards

(30 cards)

1
Q

What is Glaucoma?

A

• Glaucoma is a group of ocular disorders united by a clinically characteristic intraocular pressure-associated optic neuropathy.

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2
Q

• Two main types of Glaucoma

A

– Open-angle glaucoma (>70% of all Glaucoma cases)
» Chronic condition – may be no symptoms until vision impaired

– Angle-closure glaucoma
prognosis is worse
» Often diagnosed during acute, painful medical emergency
» Acutely raised IOP can rapidly cause nerve damage - worse prognosis than OAG

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3
Q

what results in a glaucoma

A

• Impairment in aqueous humor outflow results in elevation of the intraocular pressure (IOP)
– Increased pressure leads to damage to optic nerves, reduced peripheral vision, and eventually blindness

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4
Q

Ciliary body role

A

aq humor produced in ciliary body behind iris

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5
Q

Canal of Schlemm

A

drains liquid from eye

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6
Q

Uveoscleral outflow

A

alternative route to drain aq humor

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7
Q

Drainage Routes for Aqueous Humor

A
  • Conventional outflow pathway via the trabecular network & Schlemm’s canal
  • The uveoscleral outflow pathway (avoids trabecular meshwork)
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8
Q

• Primary closed angle (or angle-closure)

A

– Iris presses forwards, adheres to trabecular network (closes the angle)
and impedes outflow
– Leads to acute but large increase in IOP rapidly causing nerve damage
– Less common but serious – 26% of cases of glaucoma, nearly half of cases of glaucoma-related blindness

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9
Q

which condition is harder to diagnose

A

Primary open angle glaucoma

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10
Q

Open angle Glaucoma leads to

A

large angle between iris and front of the eye. access to trabecular meshwork is open

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11
Q

Glaucoma pathophysiology - Summary

A

• Glaucoma caused by optic nerve damage, normally secondary to increased ocular pressure
• Ocular pressure increased by altered balance between aqueous humor production and outflow
– Usually due to impaired outflow – Two routes of AH outflow
• Several types of glaucoma, but major distinction between open- angle & angle-closure types

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12
Q

what causes loss of eye vision

A

optic nerve damage

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13
Q

Overview of Therapeutic Strategies - OAG

A

Open Angle Glaucoma (see King et al. BMJ 2013)
• Increase outflow
– Prostaglandin F2α analogues increase outflow through uveoscleral path
• Decrease production of aqueous humor by ciliary body – β2 antagonists
– α2 agonists
– Carbonic anhydrase inhibitors
• Surgery to increase outflow through trabecular network (traeculoplasty)

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14
Q

Overview of Therapeutic Strategies - CAG

A

Closed angle glaucoma (see Wright et al. Acta Ophthalmologica 2016)
• Primary management to acutely reduce IOP – Mannitol po, acetazolomide iv
• Miotics - open angle & allow increased trabecular outflow
• IOP control using aqueous suppression & prostaglandins as for Open Angle Glaucoma
• Surgery to reduce pressure difference between anterior & posterior chambers
Slide 15
(iridotomy or iridoplasty)

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15
Q

how does manitol work

A

manitol has osomotic affects to decrease outflow of aq humor

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16
Q

how do miotics work

A

miotics cause iris to contract and pupils to shrink, this pulls iris away from the eye

17
Q

iridotomy

A

making a small hole

18
Q

iridoplasty

A

making larger gaps to allow liquid to flow

19
Q

Increasing Outflow – Prostaglandin F2α analogues

A

• Latanoprost, Bimatoprost, travoprost
– increase outflow through uveoscleral path
– Mechanism unclear
» Relax ciliary muscle ?
» Remodelling of extracellular matrix ?
• In general, better efficacy, fewer systemic effects, fewer contraindications than other medical approaches

• PK – Topical admin
• ADR – Topical:
» Eyelash growth
» Irritation
» Iris pigmentation (brown)
– Systemic
» bronchospasm, hypertension
• Cautions – Asthma
• Interactions
– Hypotensive drugs
20
Q

Decreasing aqueous humor production How is AH produced?

A

draw

  • Aqueous humor is produced by non-pigmented epithelia of the ciliary body
  • Water is osmotically pumped into aqueous humor. Osmotic gradient is produced by Na+/K+ ATPase
  • Na+ and Cl- supplied from stroma via antiports in pigmented epithelial cells – electrochemical balance maintained by export of H+ and HCO3- produced by carbonic anhydrase
21
Q

Adrenergics & AH production

A
  1. Increasing cAMP increases AH production
  2. B-adrenergic activation increases cAMP production via Gs – B-adrenergic antagonists therefore reduce AH production
  3. a-adrenergic activation decreases cAMP production via Gi – a -adrenergic agonists directly reduce AH production
  4. a-adrenergic activation also reduces NE release from sympathetic nerves
    – a -adrenergic agonists indirectly reduce AH production by reduced B-adrenergic activation
22
Q

Glaucome therpeutics B-adrenoceptor antagonists (1)

A

OAG
• B receptors in eye are primarily B2
– regulate production of aqueous humor by ciliary body
– Decrease blood flow to eye – reducing fluid available to produce aqueous humor

• Drugs
– Timolol, levobunolol, carteolol - antagonise
- betaxolol - B1 selecttive
» Less efficacious – (B2 in eye)-but avoid effects on airway (B2 mediated)
» Useful in patients with asthma
• PK - TOPICAL ADMIN

23
Q

Glaucoma therapeutics B-adrenoceptor antagonists (2)

A
• ADR 
– Resulting from systemic exposure
– Bronchospasm
– Bradycardia
• Caution
– Systemic exposure may result so need to consider cautions associated with enteral/parenteral administration
– Asthma – see above
• Contraindications
– Systemic exposure may result so need to consider contraindications associated with enteral/parenteral administration
– Eg bradycardia, heart block, heart failure 
• Drug interactions
– Other B-adrenoceptor antagonists 
– Ca2+ channel antagonists
– Cardiac glycosides
24
Q

α2 Agonist - Brimonidine

A

• Mechanism:
– Pre-synaptic receptors inhibit NA release (sympathetic nervous system)
– Activation of α2 receptors on ciliary body directly inhibits formation of aqueous humor
• PK & ADR’s
– Topical admin therefore systematic ADR’s avoided

25
Carbonic anhydrase inhibitors
OAG • Brinzolamide, dorzolamide, acetazolomide – Inhibit bicarbonate formation and hence fluid transport • PK – Topical: Brinzolamide/dorzolamide (p.o. acetazolamide – “final resort”) – Renal elimination • ADR – Acetazolamide - paresthesia, hypokalaemia + acidosis (see diuretics lecture!) – Dorzolamide/Brinzolamide: fewer - see PK! • Caution – Avoid in renal insufficiency (inhibits elimination) • Contraindications – Acetazolamide is a sulfonamide – avoid if hypersensitive • Drug interactions – Digoxin – see slide
26
Closed Angle Glaucoma Therapeutics
Miotics • Pilocarpine – Muscarinic agonist – Induces contraction of constrictor muscle in the iris – opens drainage channel – Promotes aqueous outflow • Caution – Retinal detachment can occur – examination advised first • ADR – Myopia (blurred vision) leading to headache, brow-ache with prolonged use Mannitol • Reduces the secretion of fluid into the eye by osmotic effects • ADR – electrolyte imbalances, hypotension, fluid imbalance
27
β antagonist contraindication in heart block
Heart block – signals through AV node are slowed. A β antagonist could make this worse!
28
Closed angle Glaucoma leads to
iris pushed forward, much smaller angle. Occurs due to shortages between front and back of the eye, catarachts
29
Primary open angle glaucoma
– Most common, but few obvious structural changes – Angle is normal but outflow of aqueous humor is reduced e.g. by blockages in trabecular meshwork, Schlemm’s canal or veins draining the eye – Increase in IOP less than in closed-angle glaucoma but causes nervve damage over long time period
30
Aqueous humor production
• Aqueous humor produced by ciliary body – 3mL /day, continually by ultrafilatrion from arterial blood + active secretion – Passes from posterior to anterior chamber through the pupil – 90% drains via trabecular meshwork and canal of Schlemm into episcleral vein – 10% drains via uveoscleral outflow (under ciliary muscle into choroidal vessels) Provides two therapeutic strategies • Intraocculuar pressure – normally 10-20 mm Hg – increased in glaucoma – Determined by: » rate of production of aqueous humor » rate of drainage of aqueous humor – Increased pressure causes damage to retina/optic nerve