L48 Aqueous Production and Drainage

Question 1

Why is the anterior chamber depth an important measurement?

Answer 1

It determines your risk of developing glaucoma.

Question 2

What is the average anterior chamber size?

Answer 2

11.3-11.4 mm in diameter

Question 3

Which patients have a larger anterior chamber depth?

Answer 3

Depth greater in myopes and shallower in hyperopes

Question 4

How does the anterior chamber depth and drainage angle vary with age?

Answer 4

Depth reduces with age and drainage angle becomes narrower.

Question 5

What does Inflammation of anterior uvea (Iris (iritis) /ciliary body) cause?

Answer 5

Causes a breakdown of the blood-aqueous barrier.

Question 6

What does Inflammation of anterior uvea (Iris /ciliary body) cause?

Answer 6

Causes a breakdown of the blood-aqueous barrier.

Question 7

Describe the similarities and differences between blood plasma and aqueous humour and why this is the case.

Answer 7

Electrolyte composition of aqueous is similar to plasma Differs in the composition of certain organic solutes (e.g. ascorbate (this is an antioxidant as eye is succeptible to eye oxidant damage) and lactate- (because cornea and lens are throwing these out)). To reduce scatter the aqueous contains very low levels of protein (<1% plasma) maintained by the blood aqueous barrier. The Similarities are due to aqueous humour being derived from blood plasma.

Question 8

Describe the similarities and differences between blood plasma and aqueous humour and why this is the case.

Answer 8

Electrolyte composition of aqueous is similar to plasma Differs in the composition of certain organic solutes (e.g. ascorbate (this is an antioxidant as eye is succeptible to eye oxidant damage) and lactate- (because cornea and lens are throwing these out)). To reduce scatter the aqueous contains very low levels of protein (<1% plasma) maintained by the blood aqueous barrier. The Similarities are due to aqueous humour being derived from blood plasma.

Question 9

What can be seen in iritus (inflammation of the iris)?

Answer 9

In the stages of inflammation you generate these inflammatory cells, (e.g. neutrophils , lymphcytes, then macrophages)- these cells aggregate then deposit themselves on the back surface of the cornea once they have done their job. This causes light to scatter and so can be seen in slit lamp- This is manifest clinically as ‘flare’.

Question 10

The stroma of the ciliary body contains 74% protein whereas the aqueous humour contains 1% proetin - what do we call the thing that stops the protein getting into the aqueous humour?

Answer 10

The blood aqueous barrier.

Question 11

What is the aqueous humour produced by and how does it move through the anterior SEGMENT?

Answer 11

It is produced by the Plars Plicata of the ciliary body into the posterior chamber. From here it passes through the pupil into the anterior chamber. It then drains at the irido-corneal angle (effectively turning to blood).

It follows conventional and uveoscleral outflow pathways.

Question 12

What are the four layers of the ciliary body?

Answer 12

Ciliary epithelium

Ciliary Stroma

Ciliary muscle

Supracillaris

Question 13

What does the ciliary epithelium consist of?

Answer 13

•Ciliary epithelium consists of a double epithelial layer (PE=pigment epithelium, NPE=non-pigmented epithelium)

Question 14

True or false - The stroma of ciliary process contains numerous fenestrated capillaries.

Answer 14

True

Question 15

What are the characteristics of the ciliary epithelium?

Answer 15

• Pigmented and non-pigmented cells joined apex to apex and that means they have a basement membrane on either side.
• Both cells show features of a secretory epithelium: numerous mitochondria, the plasma membrane of the cells isn’t flat there is a distinct marking of it being infolded (this is an adaption)- this is to increase surface area for the transport of water, ions and small molecules.
• A variety of cell junctions are present: desmosomes, gap junctions (allow electrical and metabolic (passing of molecules) coupling between cells), and tight junctions.

Question 16

What is one of the components of the blood-aqueous barrier?

Answer 16

Desmosomes between non pigmented epithelium (NPE) - they don’t allow the proteins to pass through.

Question 17

What is the BASIC mechanism of Aqueous production?

Answer 17

[Stroma in this case refers to blood vessels where the raw materials are derived].

• PE and NPE act as a functional unit in aqueous production
• Aqueous formation involves metabolically driven ion transport systems
• Ions (sodium, potassium, and bicarbonate ions) are transported actively from the stroma into the pigmented epithelium (an osmotic gradient is created which causes osmotic water flux) and then via gap junctions into the NPE
• Final stage is the active transport from the NPE into the stroma

Question 18

What is the important enzyme in the ciliary epithelium which generates the bicarbonate ions for the transportation into the aqueous production?

Answer 18

Carbonic Anhydrase

Question 19

What is aqueous production regulated by?

Answer 19

The autonomic nervous system specifically the sympathetic part of the autonomic nervous system

Question 20

How do carbonic anhydrase inhibitors affect intra-ocular pressure(IOP)?

Answer 20

Intra-ocular pressure is dependant on rate of production and outflow of the aqueous humour. Carbonic anhydrase inhibitors reduce the amount of bicarbonate available for transport and aqueous production and thereby reduce IOP.

Question 21

What do most of the drugs that reduce IOP interact with and why?

Answer 21

•Most of the drugs which reduce IOP interact with adrenergic receptors e.g beta blockers, alpha agonists. This is because Aqueous production is regulated by the autonomic nervous system

Question 22

How can external features of the pathway involved in aqueous drainage (i.e. the drainage angle) be visualised and why can we only use this method?

Answer 22

Using gonioscopy - we use a special lens called a gonioscope. This is basically a special contact lens that sits on an anaesthetised eye. This lens has a little angled mirror in it and what you are effectively doing is looking into this little mirror that is angled in such a way you are looking directly at the drainage angle. Thus you can see the reflection of the drainage angle. This is the gold standard.

This method must be used because by using conventional optical instruments you can’t see the angle.

Question 23

What does the majority of the aqueous drain through?

What is the alternative pathway and how much drainage does that account for?

Answer 23

• Majority of aqueous (70-90%) drains though the trabecular meshwork/ canal of Schlemm route (conventional pathway).
• An alternative uveo-scleral pathway accounts for 10-30% of aqueous outflow

Question 24

What does the conventional aqueous pathway consist of (in sequence)?

Answer 24

• Trabecular meshwork
• Canal of Schlemm
• Intra-scleral venous plexus
• Episcleral veins

Question 25

Structurally the trabecular meshwork consists of three parts - what are they?

Answer 25

–Uveal trabeculae (labelled in diagram as TM)

–Corneo-scleral trabeculae (labelled in diagram as COS)

–Juxta-canalicular layer

Question 26

What does the trabecular meshwork act as?

Answer 26

•Trabecular meshwork acts as a filter AND provides the resistance (to outflow) for the generation of an IOP

Question 27

What is a trabecular meshwork?

Answer 27

A bundle of collagen fibres with cells around them.

(have holes within them for aqueous to pass through)

Question 28

Why is the Juxta-canalicular layer (JCT) a distinct layer and key in providing the resistance to drainage outflow?

Answer 28

JCT is a very distinct layer as it consists of lots of dendritic cells and a lot of extra-cellular matrix which the aqueous humour has to pass through.

Therefore that’s where most of the resistance to the outflow of aqueous drainage resides.

[COS in diagram depicts where canal of schlem starts]

Question 29

What is the canal of Schlem?

Answer 29

• A Circular venous channel (not filled with blood)- it is filled with aqueous humour.
• Lined by a single layer of endothelial cells

Question 30

How are endothelial cells of the inner wall of the canal of Schlem linked together?

Answer 30

•Endothelial cells of the inner wall of the canal of Schlemm linked by tight junctions

Question 31

What two types of pathways/(pores) does aqueous humour pass through in the canal of Schlem if tight junctions are present (remember tight junctions don’t allow molecules to pass through)?

Answer 31

• Paracellular (pores)/pathway - between cells
• Transcellular (pores)/pathway -through cells

Question 32

Where do paracellular pores occur?

Answer 32

At cell junctions

Question 33

How does a transcellular pore pathway work?

Answer 33

Step 1 - B in the diagram - you get invagination of basal layer - a little vacuole forms.

Step 2 - C in diagram - that vacuole becomes bigger called a giant vacuole.

Step 3- It breaks through to the surface allowing aqueous to pass through

Question 34

Where do Transcellular pores occur?

Answer 34

They occur preferentially at sites of giant vacuole formation

Question 35

What are the two ways the aqueous humour passes into the blood after the canal of Schlem (part of the conventional route) ?

Answer 35

Typically way:

• Collector channels drain from the canal of Schlemm into the intrascleral venous plexus. blood mixes with aqueous here.
• The intrascleral venous plexus drains into episcleral veins

The non-typical way it happens:

Aqueous veins (which aren’t filled with blood) allow direct communication from the canal of Schlemm to the ocular surface. A pressure gradient exists from the anterior chamber to the ocular surface.

Question 36

Why isn’t the canal of Schlem filled with blood if the Intrascleral venous plexus (which contains blood) is linked to the canal of Schlemm via connector channels?

Answer 36

The reason is that there is a pressure gradient and things are therefore, flowing towards the ocular surface (remember that the intrascleral venous plexus leads to occular surface) thus there is no scope for backflow because pressure driving forwards is so much higher than any pressure that would bring it back.

Question 37

What is the Uveo-scleral pathway and what happens in it?

Answer 37

• It is an alternative pathway for aqueous outflow that is pressure independent.
• Aqueous enters the ciliary body and passes between ciliary muscle fibres into supra-ciliary and suprachoroidal spaces.
• Pressure lowering action of prostaglandin analogues e.g. Latanaprost are thought to be due to enhanced uveo-scleral outflow

Question 38

By what contraction can aqueous drainage be regulated and how does this work?

Answer 38

• Aqueous outflow can be regulated by active contraction of the ciliary muscle (thus can be linked to accommodation) and also trabecular cells through modulation of their actomyosin system (basically a fancy way of saying actin and myosin working together to allow for contraction)
• Contraction of the ciliary muscle expands the trabecular meshwork and increases outflow and decrease IOP
• Contraction of trabecular cells decreases outflow and increases IOP

Question 39

Why were intraocular pressure lowering drugs, prostaglandin analogues (e.g. Latanaprost) found to later be so effective?

Answer 39

They are thought to be due to enhanced uveo-scleral outflow.

(As in that they enhance the uveo-scleral pathway)

Question 40

What is glaucoma associated with?

Answer 40

•Glaucoma is associated with an increased resistance to outflow

Question 41

What is primary open-angle glaucoma caused by?

Answer 41

A higher than normal outflow resistance (to aqueous drainage) of the JCT/ inner wall region.

This is thought to changes to the cells of the JCT or extracellular matrix.

Question 42

Why is it difficult to decipher the cause (and what are these suspected causes) of Primary open angle glaucoma (POAG)?

Answer 42

It is thought to be due to a change in the chemical structure of matrix or ‘plaque-like’ deposits in the JCT.

However, it is difficult to pinpoint as changes in outflow pathway in POAG are very similar to those caused simply by aging.

Question 43

How can secondary glaucomas arise?

Answer 43

•Secondary glaucomas can arise from intertrabecular spaces being blocked by cellular or non-cellular material

Question 44

How can drainage in patients with glaucoma be improved?

Answer 44

Using eyedrops- need eye drops for the rest of their lives.

Selective laser trabeculoplasty - using a laser to burn holes in the trabecular meshwork (basically opening the system and reduce resistance).

Trabeculectomy- a complicated procedure where you basically create a new channel pathway.

Minimally invasive glaucoma surgery (MIGS)

Question 45

What is a disadvantage of using eyedrops to treat glaucoma in patients?

Answer 45

The patient needs to take eye drops for the rest of their life.

Question 46

What are the advantages of Selective laser trabeculoplasty?

Answer 46

It is actually relatively non-invasive - doesn’t require any anesthetic.

Patients don’t need eye drops for three years.

Question 47

What are being used to open channels in the trabecular meshwork (Minimally invasive glaucoma surgeries) in order to reduce resistance to drainage?

Answer 47

Stents (like the type used in the heart to widen narrow arteries but obviously much much smaller versions).