BS - Ocular Manifestations of Embryological Defects - Week 4

Question 1

Define congenital.

Answer 1

Relating to a condition that is present from birth as a result of either heredity or environmental influences.

Question 2

What is the prevalence of congenital ocular disease in Australia?

Answer 2

<1.5% of all congenital diseases.

Question 3

Name the 5 types of congenital disorders affecting the eye.

Answer 3

Phakomatoses
Chromosomal
Infectious
Drug Embryopathy
Other

Question 4

Describe the congenital phakomatoses disorders affecting the eye, and whether it is inherited (3).

Answer 4

• Benign congenital tumours - birthmarks
• Overgrown tissue of ectodermal tissue
• Mostly inherited, can be sporadic

Question 5

Describe the congenital chromosomal disorders affecting the eye, and whether it is inherited (3).

Answer 5

• Chromosomal abnormalities (extra chromosomes or missing parts) or;
• Minor gene sequence anomalies (mutations)
• Inherited by definition, but may be ‘acquired’ during meiosis

Question 6

Describe the congenital infectious disorders affecting the eye, and whether it is inherited.

Answer 6

Infectious agents such as viruses, bacteria, and protozoa, adversely influencing foetal development.
Is acquired.

Question 7

Describe the congenital drug embryopathy disorders affecting the eye, and whether it is inherited.

Answer 7

Maternal drug use (therapeutic or recreational) that influences foetal development.
Is aqcuired

Question 8

What is Sturge-Weber syndrome, and what is it characterised by? What nerve is associated with this condition?

Answer 8

Sporadic congenital neurocutaneous disorder characterised by a port-wine stain affecting the skin in the distribution of the ophthalmic branch of the trigeminal nerve D1.

Question 9

Name 3 skin pathologies associated with Sturge-Weber syndrome.

Answer 9

Port-wine stain
Capilary haemangioma
Cutaneous naevi

Question 10

Name 2 ocular pathologies associated with Sturge-Weber syndrome.

Answer 10

Choroidal haemangioma

Glaucoma

Question 11

Name 5 CNS disorders associated with Sturge-Weber syndrome.

Answer 11

Siezures
Epilepsy
Hemiparesis
Retardation
Cerebral angioma

Question 12

Consider Sturge-Weber syndrome. Which pathology affecting which part of the body would be considered the greatest risk?

Answer 12

If the port-wine stain affects the individual’s upper eyelid.

Question 13

Consider the pathologies of Sturge-Weber syndrome. Do they all manifest at the same time?

Answer 13

No (except the port-wine stain, which is characteristic)

Question 14

Differentiate between angioma and haemangioma.

Answer 14

Both are vasculature tumours.
Angioma includes:
-Lymphangioma (lymph vessels)
-Haemangioma (vessel walls)
-Telangiectasia/ectasia (tissue surrounding vessels)

Question 15

Name 3 histopathologies of lid angiomatosis.

Answer 15

Many capillaries
Plump vascular endothelial cells
Fibrovascular tumour (usually benign)

Question 16

Describe a pathology of Sturge-Weber syndrome that can lead to congenital glaucoma.

Answer 16

Anomalous vascularity in place of the Canal of Schlemm.

Question 17

What two types of angiomas are present in Sturge-Weber syndrome.

Answer 17

Ocular and orbital.

Question 18

Consider the histopathology of Sturge-Weber syndrome. What separates many endothelial vascular structures?

Answer 18

CT septa

Question 19

What type of congenital condition is Sturge-Weber syndrome?

Answer 19

Phakomatoses

Question 20

What type of congenital condition is Patau’s syndrome, and what is it caused by?

Answer 20

Chromosomal, caused by a trisomy of chromosome 13.

Question 21

What is the prevalence of Patau’s and Down’s syndrome?

Answer 21

Patau’s - 1/10,000

Down’s - 1/700

Question 22

Name 5 severe ocular findings associated with Patau’s syndrome.

Answer 22

Colobomq
Microphthalmos
Glaucoma
Retinal dysplasia
Corneal dysgenesis

Question 23

Consider coloboma in Patau’s syndrome. What is the causative mechanism associated with this pathology (2)?

Answer 23

Undifferentiated mesenchyme and cartilage in place of ciliary bodies

Question 24

What is the prevalence of congenital coloboma?

Answer 24

1/10,000

Question 25

Describe optic disc coloboma (2). What forms over the fissure?

Answer 25

Incomplete retinal/choroidal closure and condensation of the scleral mesenchyme over the gap.
A staphyloma-like structure forms over it.

Question 26

Consider optic disc coloboma. Are they typically unstable, and does it affect vision? What does it put one at risk of?

Answer 26

Usually stable.

However it will produce VF defects, and there is a risk of retinal detachment.

Question 27

Are cases of coloboma typically isolated or syndromic? Does this affect the likely cause?

Answer 27

It can be either isolated or syndromic, a genetic cause is more likely if syndromic.

Question 28

Name the three inheritance patterns of coloboma.

Answer 28

Autosomal dominant
Autosomal recessive
X-linked

Question 29

Name 6 ocular co-morbidities of coloboma.

Answer 29

Glaucoma
Microphthalmia
Retinal dysplasia
Posterior staphyloma
Heterochromia
Nystagmus

Question 30

How does a congenital rubella infection occur? When is it most likely?

Answer 30

When the virus crosses the placenta to the embryo.

Most likely to occur during the first trimester.

Question 31

When are developing lens in a foetus most susceptible to a congenital rubella infection and why (2)? What does the virus do to the lens, and what does this cause?

Answer 31

Lens is most vulnerable before the capsule is formed during weeks 4-7, where it is the growth of primary lens fibres.
The virus destroys and liquefies embryonic cells, and causes congenital cataracts.

Question 32

How long can a live rubella virus remain in the lens for, and what implications does this have for lens surgery (2)?

Answer 32

Up to three years.

Surgery may release the virus, and later cause endophthalmitis or cataracts.

Question 33

What three retinal pathologies are associated with congenital rubella infection, and when do these occur?

Answer 33

Patchy atrophy
Compensatory RPE hypertrophy
Occurs during retinal development.
The outer retina becomes necrotic.

Question 34

Consider an eye affected by congenital rubella infection. What characteristic appearance can be seen on a fundus exam?

Answer 34

Salt and pepper appearance.

Question 35

What is the prevalence of foetal alcohol syndrome in Australia?

Answer 35

1.7-4.7/1,000

Question 36

Name 6 ocular pathologies associated foetal alcohol syndrome.

Answer 36

Narrow palpebral fissure
Ptosis
Strabismus
Microcornea
Cloudy cornea
Optic nerve hypoplasia

Question 37

How does total optic nerve hypoplasia appear on examination?

Answer 37

Double ring appearance

Question 38

Describe two causative mechanisms for a cloudy cornea in foetal alcohol syndrome.

Answer 38

• Disrupted corneal collagen fibre bundles

- Lack of corneal collagen layers, indicating abnormal collagen production

Question 39

What is the prevalence of congenital cataracts in Victoria? What percentage is hereditary?

Answer 39

2.2/10,000

25% is hereditary

Question 40

Name the four manifestations of congenital cataracts.

Do they all affect vision?

Answer 40

Anterior
Posterior polar
Sutural
Nuclear
Some significantly affect vision, some little to none.

Question 41

Which type of congenital cataracts is most likely to be associated with early embryological development of the lens fibres?

Answer 41

Nuclear

Question 42

By mutations to what protein genes can nuclear cataracts be inherited?

Answer 42

The γ-crystallin gene, which is expressed highly in the developing nucleus, but less so in the mature lens.

Question 43

Describe three causative mechanisms of congenital polar cataracts.

Answer 43

• Anomaly in the neighbouring tissue and the vitrous

- Incomplete atrophy of the vasculosum lentis, leaving a hyaloid remnant

Question 44

Consider the vasculosum lentis. Explain how incomplete atrophy can result in polar cataracts.

Answer 44

It leaves behind a hyaloid remnant that affects posterior cortical metabolism, resulting in lens fibre necrosis, and the degeneration of the posterior subcapsular cortex.

Question 45

Describe a Mittendorf dot, where it can be found, what it is caused by, and whether it affects vision.

Answer 45

It is a posterior pole opacity associated with a remnant hyaloid artery.
Due to the underdevelopment of fibres, resulting in a small cleft at the position of the remnant insertion into the lens capsule.
Visually very insignificant.

Question 46

What type of congenital disorders are congenital optic head atrophy typically?

Answer 46

Often genetic, but may also be infective

Question 47

How would an optic atrophy appear on examination and why?

Answer 47

Pale disc due to atrophied nerve cells allowing more light to reach the lamina cribrosa which reflects the light.

Question 48

How do the meninges appear in an eye with optic atrophy and why? Name one other condition in which this is seen.

Answer 48

Optic nerve shrinks from the meninges, leaving an abnormally large sub-arachnoidal space.
Also seen in glaucoma.

Question 49

Name two mechanisms of aqcuired optic atrophy, and give an example of each.

Answer 49

Ascending (to the CNS) - glaucoma
Descending (from the CNS) - hydrocephalus
Depends on the position of the lesion

Question 50

Namea likely mechanism of inherited optic atrophy.

Answer 50

Various causes but often affects mitochondrial metabolism in retinal ganglion cell axons.

Question 51

Name the best understood optic atrophy condition, what it is caused by, how it is passed on, and which cells it manifests in.

Answer 51

Leber’s hereditary optic neuropathy, caused by mitochondrial DNA mutation.
Only inherited from the mother.
Only manifests in cells where mitochondria are working excessively.
Other factors are involved.

Question 52

During foetal development, when does myelination of the nerve fibres begin?

Answer 52

Once they reach the LGN at week 23

Question 53

When do nerve fibres reach the lamina cribrosa?

Answer 53

1-3 months post-natal

Question 54

What is myelin growth mediated by, where does it stop, and in what percentage does it continue to grow? What are these nerves called, and what condition is it associated with?

Answer 54

Mediated by oligodencrocytes, usually stopping at the lamina cribrosa.
In 1% of people, in continues to grow, the nerves are called myelinated or medullated nerve fibres.
Associated with trisomy 21.

Question 55

What three retinal pathologiess are associated with myelinated nerve fibres? Are they all clinically significant?

Answer 55

Retinal nerve fibre layer is thickened.
Stationary VF defects present.
Myopia.
Only the myopia and VF defects are significant.

Question 56

Why do myelinated nerve fibres occur?

Answer 56

Not well understood.

Studies suggest anomalous migration of oligodendrocyte lineage cells through the lamina cribrosa or optic nerve head.