BS - Ocular Manifestations of Embryological Defects - Week 4 Flashcards
Define congenital.
Relating to a condition that is present from birth as a result of either heredity or environmental influences.
What is the prevalence of congenital ocular disease in Australia?
<1.5% of all congenital diseases.
Name the 5 types of congenital disorders affecting the eye.
Phakomatoses Chromosomal Infectious Drug Embryopathy Other
Describe the congenital phakomatoses disorders affecting the eye, and whether it is inherited (3).
- Benign congenital tumours - birthmarks
- Overgrown tissue of ectodermal tissue
- Mostly inherited, can be sporadic
Describe the congenital chromosomal disorders affecting the eye, and whether it is inherited (3).
- Chromosomal abnormalities (extra chromosomes or missing parts) or;
- Minor gene sequence anomalies (mutations)
- Inherited by definition, but may be ‘acquired’ during meiosis
Describe the congenital infectious disorders affecting the eye, and whether it is inherited.
Infectious agents such as viruses, bacteria, and protozoa, adversely influencing foetal development.
Is acquired.
Describe the congenital drug embryopathy disorders affecting the eye, and whether it is inherited.
Maternal drug use (therapeutic or recreational) that influences foetal development.
Is aqcuired
What is Sturge-Weber syndrome, and what is it characterised by? What nerve is associated with this condition?
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.
Name 3 skin pathologies associated with Sturge-Weber syndrome.
Port-wine stain
Capilary haemangioma
Cutaneous naevi
Name 2 ocular pathologies associated with Sturge-Weber syndrome.
Choroidal haemangioma
Glaucoma
Name 5 CNS disorders associated with Sturge-Weber syndrome.
Siezures Epilepsy Hemiparesis Retardation Cerebral angioma
Consider Sturge-Weber syndrome. Which pathology affecting which part of the body would be considered the greatest risk?
If the port-wine stain affects the individual’s upper eyelid.
Consider the pathologies of Sturge-Weber syndrome. Do they all manifest at the same time?
No (except the port-wine stain, which is characteristic)
Differentiate between angioma and haemangioma.
Both are vasculature tumours. Angioma includes: -Lymphangioma (lymph vessels) -Haemangioma (vessel walls) -Telangiectasia/ectasia (tissue surrounding vessels)
Name 3 histopathologies of lid angiomatosis.
Many capillaries Plump vascular endothelial cells Fibrovascular tumour (usually benign)
Describe a pathology of Sturge-Weber syndrome that can lead to congenital glaucoma.
Anomalous vascularity in place of the Canal of Schlemm.
What two types of angiomas are present in Sturge-Weber syndrome.
Ocular and orbital.
Consider the histopathology of Sturge-Weber syndrome. What separates many endothelial vascular structures?
CT septa
What type of congenital condition is Sturge-Weber syndrome?
Phakomatoses
What type of congenital condition is Patau’s syndrome, and what is it caused by?
Chromosomal, caused by a trisomy of chromosome 13.
What is the prevalence of Patau’s and Down’s syndrome?
Patau’s - 1/10,000
Down’s - 1/700
Name 5 severe ocular findings associated with Patau’s syndrome.
Colobomq Microphthalmos Glaucoma Retinal dysplasia Corneal dysgenesis
Consider coloboma in Patau’s syndrome. What is the causative mechanism associated with this pathology (2)?
Undifferentiated mesenchyme and cartilage in place of ciliary bodies
What is the prevalence of congenital coloboma?
1/10,000
Describe optic disc coloboma (2). What forms over the fissure?
Incomplete retinal/choroidal closure and condensation of the scleral mesenchyme over the gap.
A staphyloma-like structure forms over it.
Consider optic disc coloboma. Are they typically unstable, and does it affect vision? What does it put one at risk of?
Usually stable.
However it will produce VF defects, and there is a risk of retinal detachment.
Are cases of coloboma typically isolated or syndromic? Does this affect the likely cause?
It can be either isolated or syndromic, a genetic cause is more likely if syndromic.
Name the three inheritance patterns of coloboma.
Autosomal dominant
Autosomal recessive
X-linked
Name 6 ocular co-morbidities of coloboma.
Glaucoma Microphthalmia Retinal dysplasia Posterior staphyloma Heterochromia Nystagmus
How does a congenital rubella infection occur? When is it most likely?
When the virus crosses the placenta to the embryo.
Most likely to occur during the first trimester.
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?
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.
How long can a live rubella virus remain in the lens for, and what implications does this have for lens surgery (2)?
Up to three years.
Surgery may release the virus, and later cause endophthalmitis or cataracts.
What three retinal pathologies are associated with congenital rubella infection, and when do these occur?
Patchy atrophy
Compensatory RPE hypertrophy
Occurs during retinal development.
The outer retina becomes necrotic.
Consider an eye affected by congenital rubella infection. What characteristic appearance can be seen on a fundus exam?
Salt and pepper appearance.
What is the prevalence of foetal alcohol syndrome in Australia?
1.7-4.7/1,000
Name 6 ocular pathologies associated foetal alcohol syndrome.
Narrow palpebral fissure Ptosis Strabismus Microcornea Cloudy cornea Optic nerve hypoplasia
How does total optic nerve hypoplasia appear on examination?
Double ring appearance
Describe two causative mechanisms for a cloudy cornea in foetal alcohol syndrome.
- Disrupted corneal collagen fibre bundles
- Lack of corneal collagen layers, indicating abnormal collagen production
What is the prevalence of congenital cataracts in Victoria? What percentage is hereditary?
2.2/10,000
25% is hereditary
Name the four manifestations of congenital cataracts.
Do they all affect vision?
Anterior Posterior polar Sutural Nuclear Some significantly affect vision, some little to none.
Which type of congenital cataracts is most likely to be associated with early embryological development of the lens fibres?
Nuclear
By mutations to what protein genes can nuclear cataracts be inherited?
The γ-crystallin gene, which is expressed highly in the developing nucleus, but less so in the mature lens.
Describe three causative mechanisms of congenital polar cataracts.
- Anomaly in the neighbouring tissue and the vitrous
- Incomplete atrophy of the vasculosum lentis, leaving a hyaloid remnant
Consider the vasculosum lentis. Explain how incomplete atrophy can result in polar cataracts.
It leaves behind a hyaloid remnant that affects posterior cortical metabolism, resulting in lens fibre necrosis, and the degeneration of the posterior subcapsular cortex.
Describe a Mittendorf dot, where it can be found, what it is caused by, and whether it affects vision.
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.
What type of congenital disorders are congenital optic head atrophy typically?
Often genetic, but may also be infective
How would an optic atrophy appear on examination and why?
Pale disc due to atrophied nerve cells allowing more light to reach the lamina cribrosa which reflects the light.
How do the meninges appear in an eye with optic atrophy and why? Name one other condition in which this is seen.
Optic nerve shrinks from the meninges, leaving an abnormally large sub-arachnoidal space.
Also seen in glaucoma.
Name two mechanisms of aqcuired optic atrophy, and give an example of each.
Ascending (to the CNS) - glaucoma
Descending (from the CNS) - hydrocephalus
Depends on the position of the lesion
Namea likely mechanism of inherited optic atrophy.
Various causes but often affects mitochondrial metabolism in retinal ganglion cell axons.
Name the best understood optic atrophy condition, what it is caused by, how it is passed on, and which cells it manifests in.
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.
During foetal development, when does myelination of the nerve fibres begin?
Once they reach the LGN at week 23
When do nerve fibres reach the lamina cribrosa?
1-3 months post-natal
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?
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.
What three retinal pathologiess are associated with myelinated nerve fibres? Are they all clinically significant?
Retinal nerve fibre layer is thickened.
Stationary VF defects present.
Myopia.
Only the myopia and VF defects are significant.
Why do myelinated nerve fibres occur?
Not well understood.
Studies suggest anomalous migration of oligodendrocyte lineage cells through the lamina cribrosa or optic nerve head.
