Myopia (Nature) - Week 8

Question 1

Prevalence of Myopia?

Answer 1

Most common eye disorder

- affects ~30% of western populations and up to 80% of asian populations

Question 2

How do you classify high myopia?

Answer 2

More than -ve 6.0 diopters or axial length over 26.5mm

Question 3

What is the current prevailing theory of the mechanism for Myopia?

Answer 3

1. Ocular growth triggered by a visually evoked signalling cascade (retina)
2. Signaling cascade traverses the RPE + choroid and terminates in the sclera
3. Remodeling of scleral ECM promotes eye elongation

Question 4

How has genetic research of myopia grown over time?

Answer 4

16 studies in 1996, 84 studies in 2015

124 to 240 if including retinitis pigmentosa

Question 5

Can twin study correlation be accounted for by growing up in the same environment?

Answer 5

No. Only 0.5% can be accounted for this way

Question 6

How can we investigate the genetic causes of Myopia?

Answer 6

Perform Twin studies:

- look at monozygotic vs dizygotic twins

Question 7

Which type of twin was found to have higher correlation to myopia? Monozygotes or Dizygotes?

Answer 7

Monozygotes

Question 8

What is GWAS and what does it investigate?

Answer 8

Genome Wide Association Studies 
looks at:
- microsatellites/short tandem repeats
- SNPs
- Meta-analysis
- twins, families, controls vs affected
- different ethnic origins
- low medium or high grade myopia

Question 9

Describe what we have found genetically for High grade Myopia.

Answer 9

• greater than 30 locations
• greater than 20 loci (named/recognised)
• greater than 40 implicated genes

Question 10

Describe the CREAM study.

Answer 10

Consortium for Refractive Error and Myopia

• 23 and me study
• saliva swab kits for DNA
• crowd sourced open data
• largest GWAS of refractive phenotypes

Question 11

Describe 2 gene loci implicated in high myopia.

Answer 11

• greater than 20 loci implicated
  e.g.
  MYP1: affects x-chromosome, may also involve CVD effects
  MYP2: autosomal dominant

Question 12

List some of the candidate gens implicated in high myopia:

Answer 12

MMP1 and 2

• breaks down collagen (ECM)
• involved in signalling cascades (type 1/2 collagen)

Myocilin (MYOC)
- also involved with glaucoma

Pax 6

Question 13

List the functional implications by the genetic variants in myopia: (5)

Answer 13

• neurotransmission
• ion transport
• retinoic acid metabolism
• ECM remodeling
• eye development

Question 14

How does having parents with myopia affect the risk of developing myopia?

Answer 14

One parent with myopia: 2 x risk

Both parents with myopia: 8 x risk

Question 15

How does having parents with myopia affect axial length growth?

Answer 15

One parent with myopia: 0.06mm growth

Both parents with myopia: 0.2mm growth

Question 16

In which ethnicity is the effect of both myopic parents on childhood myopic development more pronounced? East Asians or Europeans

Answer 16

East Asians

Question 17

Which has the higher correlation for myopia, siblings or parents?

Answer 17

Siblings

Question 18

List the X-linked recessive syndromic diseases associated with myopia (7)

Answer 18

• Marfan syndrome (most common)
• Stickler
• Wagner
• Albinism
• Aland Island eye disease
• Night Blindness
• Bornholm eye disease

Question 19

List the X-linked recessive non-syndromic diseases associated with myopia. What are the symptoms?

Answer 19

• anything with Xq28 gene affected

- - early age of onset (4-8yrs old) and high myopia (more than -ve 6 diopters)

Question 20

What are the features of Bornholm eye disease?

Answer 20

• very rare
• is the 1st designated high myopia locus (MYP1)
• protan and detuan defects reported
• abnormal cone responses
• High myopia, High cyl
• Optic Nerve Hypoplasia
• Also normal to slightly reduced VA