CLM - Mechanisms Regulating Ocular Growth and Refractive Error Development - Week 5 Flashcards
Define emmetropisation.
The disappearance of neonatal refractive errors which are considered normal
What is the approximate change in refraction from a newborn baby to 6-8 years of age?
From +2.00D to +0.25D
What is the average axial length of a neonatal and adult eyeball?
Neonatal - 16.5mm
Adult - 23.5mm
Describe the biological statistical method. List the four ocular components it proposes is involved in emmetropisation.
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
Does the biological statistics method have strong evidence? Explain.
There is strong evidence to suggest there is coordinated growth of the eye
What does the biological statistics method propose about large eyes?
That they have flatter corneas
What does the biological statistics method suggest drives its proposed mechanism? Explain.
Hereditary influences
It doesnt explain the role of the environment
Describe the three factors of the theory of emmetropisation what theyre important.
It proposes that three factors explain all major correlations between an eyes optical components:
Size factor
Stretch factor
Derailment factor
Describe the size factor of the theory of emmetropisation, and describe where the loadings are (2).
Bigger eyes have flatter corneas
Loadings in corneal curvaure and axial length
Describe the stretch factor of the theory of emmetropisation, and describe where the loadings are (3).
Loadings in the vitreous chamber depth, axial length, and lens power
Describe the derailment factor of the theory of emmetropisation, and describe where the loadings are (1).
Loadings in all four
Describe what the theory of emmetropisation proposes.
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.
Does the theory of emmetropisation propose both hereditary and environmental influences?
Yesd
Describe the use-abuse theory.
Suggests that the ‘abuse’ of eyes in schooling causes myopia
What is the evidence for the association of near work and myopia in humans (2)?
Strong evidence esxists, but does not provide proof of cause and effect
What does the use-abuse theory strongly support; hereditary or environmental factors as the major influence on ametropia?
Environmental
Describe the effect of lid fusion on ocular growth when the subject is grown in both light and dark conditions.
Neonatal lid fusion causes elongation when the animals are grown in light conditions
There is no effect if grown in dark conditions
Define form deprivation myopia. What concept does this support?
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
What refractive error can forced frontal field, forced lateral field, and form deprivation lead to?
Form deprivation - myopia
Forced lateral field - hyperopia
Forced frontal field - mostly myopia
With experimental induction of refractive error, what happens with the use of plus and minus lenses?
Plus - induces hyperopia by resulting in decreased axial length
Minus - induces myopia by resulting in increased axial length
What does the experimental induction of refractive error suggest?
That there is a mechanism by which the eye can recognise its own refractive state and regulate growth to achieve emmetropia.
Consider experimental induction of refractive error. What happens with the removal of the inducing lenses?
Growth was again altered to try and achieve emmetropia
Do regional changes in the eye occur due to regional visual deprivation? What does this suggest about eye growth?
Yes, it suggests that eye growth in myopia cannot be due to a global process, and is controlled via a local pathway
Consider form deprivation. To what extent can it cause myopia (2)? What does this suggest?
Causes myopia even after optic nerve section or blocade of retinal action potentials
Suggests there are local retino-scleral mechanisms that control ocular growth
What can atropine prevent?
Form deprivation myopia
What is the mechanism of action of atropine?
Broad band muscarinic receptor antagonist
Does atropine affect accommodation? Does it result in miosis or mydriasis?
Blocks accommodation and induces mydriasis
Is accommodation required to induce myopia?
No
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.
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
Does atropine have any effect on accommodation in avians?
No
Does atropine have any effect on axial length in avians? What does this mean?
Yes, it prevents axial elongation and therefor acts via a non-accommodative mechanism to prevent axial elongation
List three possible sites of action for a muscarinic antagonist in the eye.
Retina
Choroid
Sclera
hat other drug reduces axial elongation?
Pirenzipine
What does pirenzipine prevent (aside from increasing axial length) and in what manner?
Reduces myopia in a dose dependent manner
What muscarinic receptor does pirenzipine target and here are they localised? hat does this suggest?
A selective M1 antagonist which are localised in retinal and neural tissues Suggests it (and atropine) act via a retinal mechanism
What do high doses of pirenzipine result in what does this rule out?
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
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.
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
What are MT-3 and MT-7?
MT-3 - highly selective M4 antagonist
MT-7 - highly selective M1 receptor
Does MT-3 inhibit myopia in avians at physiologically relevant doses? What about MT-7? What does this suggest about how pirenzipine works?
MT-3 - yes
MT-7 - no
Therefore pirenzipine may be exerting its effects via the M4 receptor and not M1
What is ZENK, what happens with minus and plus lens, and which cells does this happen in? What does this indicate?
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
What effect does atropine have on ZENK?
It increases ZENK expression
What effect does ZENK expression have on elongation?
It slows elongation
Describe evidence that suggests the peripheral retina may play a role in modulating overall eye health and axial length.
Ablation of the fovea and leaving the peripheral retina intact still permits emmetropisation
Define relative peripheral hyperopia. What refractive error does this result in?
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).
Is relative peripheral hyperopia associated with myopia development in humans?
Yesd
What is the effect of relative peripheral myopia?
It slows axial elongation
Is myopia and its progression fully explainable by peripheral refractive effects?
No
What does more recent data suggest about whether changes in eye growth precedes or accompanies myopia onset?
It suggests changes in eye growth accompanies (rather than precede) myopia onset
Do peripheral aberration control spectacles and dual focus soft contact lenses slow axial elongation?
Yes
