CLM - Mechanisms Regulating Ocular Growth and Refractive Error Development - Week 5

Question 1

Define emmetropisation.

Answer 1

The disappearance of neonatal refractive errors which are considered normal

Question 2

What is the approximate change in refraction from a newborn baby to 6-8 years of age?

Answer 2

From +2.00D to +0.25D

Question 3

What is the average axial length of a neonatal and adult eyeball?

Answer 3

Neonatal - 16.5mm

Adult - 23.5mm

Question 4

Describe the biological statistical method. List the four ocular components it proposes is involved in emmetropisation.

Answer 4

Attempts to show that all refractive errors re due to the way which the components of the eye combine:
Axial length
Corneal power
Lens power
Anterior chamber depth

Question 5

Does the biological statistics method have strong evidence? Explain.

Answer 5

There is strong evidence to suggest there is coordinated growth of the eye

Question 6

What does the biological statistics method propose about large eyes?

Answer 6

That they have flatter corneas

Question 7

What does the biological statistics method suggest drives its proposed mechanism? Explain.

Answer 7

Hereditary influences

It doesnt explain the role of the environment

Question 8

Describe the three factors of the theory of emmetropisation what theyre important.

Answer 8

It proposes that three factors explain all major correlations between an eyes optical components:
Size factor
Stretch factor
Derailment factor

Question 9

Describe the size factor of the theory of emmetropisation, and describe where the loadings are (2).

Answer 9

Bigger eyes have flatter corneas

Loadings in corneal curvaure and axial length

Question 10

Describe the stretch factor of the theory of emmetropisation, and describe where the loadings are (3).

Answer 10

Loadings in the vitreous chamber depth, axial length, and lens power

Question 11

Describe the derailment factor of the theory of emmetropisation, and describe where the loadings are (1).

Answer 11

Loadings in all four

Question 12

Describe what the theory of emmetropisation proposes.

Answer 12

The ciliary body and choroid form an elastic envelope that limits the stretch of the sclera by counteracting IOP.
The macula supplies information regarding focus to the brain, which feedbacks information concerning the necessary degree of stretch.

Question 13

Does the theory of emmetropisation propose both hereditary and environmental influences?

Answer 13

Yesd

Question 14

Describe the use-abuse theory.

Answer 14

Suggests that the ‘abuse’ of eyes in schooling causes myopia

Question 15

What is the evidence for the association of near work and myopia in humans (2)?

Answer 15

Strong evidence esxists, but does not provide proof of cause and effect

Question 16

What does the use-abuse theory strongly support; hereditary or environmental factors as the major influence on ametropia?

Answer 16

Environmental

Question 17

Describe the effect of lid fusion on ocular growth when the subject is grown in both light and dark conditions.

Answer 17

Neonatal lid fusion causes elongation when the animals are grown in light conditions
There is no effect if grown in dark conditions

Question 18

Define form deprivation myopia. What concept does this support?

Answer 18

The effect of a blurred image on the retina is that the eye attempts to rectify the situation by elongating to obtaina clearer focus
Supports the concept that axial elongation is the default growth mechanism

Question 19

What refractive error can forced frontal field, forced lateral field, and form deprivation lead to?

Answer 19

Form deprivation - myopia
Forced lateral field - hyperopia
Forced frontal field - mostly myopia

Question 20

With experimental induction of refractive error, what happens with the use of plus and minus lenses?

Answer 20

Plus - induces hyperopia by resulting in decreased axial length
Minus - induces myopia by resulting in increased axial length

Question 21

What does the experimental induction of refractive error suggest?

Answer 21

That there is a mechanism by which the eye can recognise its own refractive state and regulate growth to achieve emmetropia.

Question 22

Consider experimental induction of refractive error. What happens with the removal of the inducing lenses?

Answer 22

Growth was again altered to try and achieve emmetropia

Question 23

Do regional changes in the eye occur due to regional visual deprivation? What does this suggest about eye growth?

Answer 23

Yes, it suggests that eye growth in myopia cannot be due to a global process, and is controlled via a local pathway

Question 24

Consider form deprivation. To what extent can it cause myopia (2)? What does this suggest?

Answer 24

Causes myopia even after optic nerve section or blocade of retinal action potentials
Suggests there are local retino-scleral mechanisms that control ocular growth

Question 25

What can atropine prevent?

Answer 25

Form deprivation myopia

Question 26

What is the mechanism of action of atropine?

Answer 26

Broad band muscarinic receptor antagonist

Question 27

Does atropine affect accommodation? Does it result in miosis or mydriasis?

Answer 27

Blocks accommodation and induces mydriasis

Question 28

Is accommodation required to induce myopia?

Answer 28

No

Question 29

Compare the ciliary muscles of avian and mammalian ciliary bodies, and describe how this information can be used to determine whether atropine’s effect on myopia is via an accommodative or non-accommodative mechanism.

Answer 29

Avian - has nicotinic receptors
Mammalian - has muscarinic receptors
If atropine acts via an accommodative mechanism to prevent myopia, it should have no effect on axial length in avians

Question 30

Does atropine have any effect on accommodation in avians?

Answer 30

No

Question 31

Does atropine have any effect on axial length in avians? What does this mean?

Answer 31

Yes, it prevents axial elongation and therefor acts via a non-accommodative mechanism to prevent axial elongation

Question 32

List three possible sites of action for a muscarinic antagonist in the eye.

Answer 32

Retina
Choroid
Sclera

Question 33

hat other drug reduces axial elongation?

Answer 33

Pirenzipine

Question 34

What does pirenzipine prevent (aside from increasing axial length) and in what manner?

Answer 34

Reduces myopia in a dose dependent manner

Question 35

What muscarinic receptor does pirenzipine target and here are they localised? hat does this suggest?

Answer 35

A selective M1 antagonist which are localised in retinal and neural tissues
Suggests it (and atropine) act via a retinal mechanism

Question 36

What do high doses of pirenzipine result in what does this rule out?

Answer 36

High doses are needed to experimentally induce myopia prevention - this doesnt rule out a role for other M receptor subtypes because M1 selectivity is lost at high doses

Question 37

Describe the density of M1 vs M4 receptors in the retina and what this can suggest about how pirenzipine and atropine exert their effects. Mention the affinity both drugs have for these subtypes.

Answer 37

Pirenzipine only has a 4-fold lower affinity for M4 than for M1
M1 receptors are scarce in the retina, and higher number M4 receptors could indicate that these drugs exert their effect via an M4 receptor

Question 38

What are MT-3 and MT-7?

Answer 38

MT-3 - highly selective M4 antagonist

MT-7 - highly selective M1 receptor

Question 39

Does MT-3 inhibit myopia in avians at physiologically relevant doses? What about MT-7? What does this suggest about how pirenzipine works?

Answer 39

MT-3 - yes
MT-7 - no
Therefore pirenzipine may be exerting its effects via the M4 receptor and not M1

Question 40

What is ZENK, what happens with minus and plus lens, and which cells does this happen in? What does this indicate?

Answer 40

A transcription factor which is donregulated in the presence of minus lenses within 30 mins of lens application
Upregulated with positive lenses
It is a proto-oncogene in retinal amacrine cells
Indicates an active, rapid change in gene expression in the retina, which responds to the sign of defocus

Question 41

What effect does atropine have on ZENK?

Answer 41

It increases ZENK expression

Question 42

What effect does ZENK expression have on elongation?

Answer 42

It slows elongation

Question 43

Describe evidence that suggests the peripheral retina may play a role in modulating overall eye health and axial length.

Answer 43

Ablation of the fovea and leaving the peripheral retina intact still permits emmetropisation

Question 44

Define relative peripheral hyperopia. What refractive error does this result in?

Answer 44

Hyperopia in the periphery only, leaving focus on the fovea intact.
Resulted in the induction of myopia (whether it is the cause of refractive error is still unkown).

Question 45

Is relative peripheral hyperopia associated with myopia development in humans?

Answer 45

Yesd

Question 46

What is the effect of relative peripheral myopia?

Answer 46

It slows axial elongation

Question 47

Is myopia and its progression fully explainable by peripheral refractive effects?

Answer 47

No

Question 48

What does more recent data suggest about whether changes in eye growth precedes or accompanies myopia onset?

Answer 48

It suggests changes in eye growth accompanies (rather than precede) myopia onset

Question 49

Do peripheral aberration control spectacles and dual focus soft contact lenses slow axial elongation?

Answer 49

Yes