Week 8: Developmental Abnormalities Embyology

Question 1

What time to errors in embryogenesis have the most profound effects usually?

Answer 1

4-6 weeks

Question 2

What is a congenital abnormality?

Answer 2

“Congenital” definition: a disease or abnormality that is present from birth

Question 3

What are some examples of congenital abnormalities?

Answer 3

1. Congenital cataracts
2. Congenital glaucoma
3. Coloboma
4. Aniridia
5. Anophthalmos and Microphthalmia
6. Peter’s Anomaly
7. Albinism

Question 4

What is congenital cataract?

Answer 4

• lens is opaque/white due to inadequate lens fibre growth
• 3-4 per 10,000 births in UK, globally causes 10% of Vision loss in kids but treatable
• can be caused by rubella infection in mum, if infected after lens develops no cataracts
• 1/4 cases dominant gene inherited
• address within 3 months or risk Amblyopia or abnormal retinal development (optic nerve-brain connections not formed properly)
• red reflex test: performed in dark room involves shining ophthalmoscope into both eyes simultaneously from 1-2 feet (NHS screening at 24-48 hrs)
• treated with intra-ocular lens or contact lens

Question 5

What is congenital glaucoma? (Congenital meaning present at birth)

Answer 5

• Adult Glaucoma is caused by abnormally high intraocular pressure (IOP), so is congenital glaucoma
  -— Can be caused by abnormal development of the iridocorneal angle structures (e.g. trabecular meshwork=controls drainage of fluid)
  -— Or caused by rubella infection or by recessive mutant genes (copy from both parents)
  —- Presents with elevated IOP, abnormally deep anterior chamber, globe enlargement, oedema, corneal opacification, anterior scleral thinning, iris atrophy and optic atrophy
  —- Symptoms - photophobia, blepharospasm (twitching) and excessive tearing
  —- If untreated, blindness occurs (due to damage to optic nerves)
  —- If diagnosed early (within 1st year of life), 80-90% of children respond well to treatment (but may be some reduced VA/VF)

Question 6

What is coloboma?

Answer 6

• occurs when the choroid fissure in the optic cup does not completely close in 7th week
• Results in defect in the inferior part of iris, giving pupil a keyhole appearance (may affect eyelids, lens, cornea, iris, ciliary body)
• can sometimes include retina, which may compromise vision (reduced visual field)
• may be caused by environmental factors, due to autosomal dominant gene

Question 7

What is Aniridia?

Answer 7

• Bilateral (both eyes) condition where iris does not develop (may be partially missing or completely absent)
• results in reduced VA, photophobia and nystagmus
• associated with other eye problems e.g. cataracts, glucoma
• mainly hereditary (mutation/deletion of PAX6 gene)
• no treatment, but most retain useful vision with ophthalmological monitoring and management

Question 8

-what is anophthalmos ?

Answer 8

Baby’s born with the absence of eyes (sometimes due to a green absence, SOX2)
Optic vesicle growth failure , or lack of closure or neural tube

Question 9

What is microphthalmia?

Answer 9

• one or both eyes are abnormally small and have an atomic malformations
• due to alcohol abuse during gestation, infections (herpes simplex, rubella) or genetics
• May cause raised IOP, cataract, poor vision, nystagmus
• in mild versions, child is long-sighted (Hypermetropia)
• patching may strengthen weaker eye

Question 10

How do people get Peters Anomaly?

Answer 10

• rare form of anterior segment dysgensis where abnormal cleavage of the anterior chamber occurs (front of eye)
• in embryogenesis, normal corneal development depends on neural crest migration (occurs in 3 distinctive waves) to produce anterior chamber structures (around week 7)
• 1st wave involves cornel endothelium formation, as neural crest cells migrate between surface ectoderm & lens
• 2nd wave = peripheral neural crest cells migrate between corneal endothelium & surface ectoderm (forms the keratocytes which create corneal stroma)
• final eave involves iris stroma formation
• any disruption of neural crest migration or separation can lead to anterior segment dysgenesis

Question 11

What is peters anomaly?

Answer 11

-Affects iris, corneal endothelium and descemet’s membrane
-characterised by a central corneal opacity (translucency or central cornea)(Leukoma) due to defects in the posterior stroma, Descemet membrane and endothelium, shallow anterior chamber
-genetic mutations (e.g. improper neural crest signalling and abnormalities in chromosomes 11, 13 and 20)
-abnormal red reflex test
-peripheral cornea is clear
-associated with cataract
Management;
-full thickness penetrating keratoplasty (corneal transplant)
-iridoplasty (gonioplasty) = low-energy laser burns to the peripheral iris to widen anterior chamber angle and/or break peripheral anterior synechiae

Question 12

What is albinism?

Answer 12

-absent/reduced tissue melanin (including ocular melanin) Proteins responsible fo fits production
-presents with iris hypo(under)pigmentation, nystagmus (rhythmic, involuntary eye movement), photophobia, strabismus (and head tilt) and refractive errors
- Foveal hypoplasia (no foveal pit), due to lack of pigment in RPE-needed for macula development. Main cause of poor vision
Management
• Limit sun exposure due to risk of squamous cell cancer (SCC) & basal cell cancers (SCC)
• Strabismus or nystagmus may benefit from eye muscle surgery or similar management
• Possibly new treatment with L-DOPA for ocular problems (Dopamine is intermediate product in melanin synthesis)