Retinal Dystrophies Part 1

Question 1

What is the cause of retinal dystrophies?

Answer 1

Mutations on chromosomes - i.e. they are inherited

Question 2

True or False- Mutations that cause retinal dystrophies can have variable expressivity/penetrance

Answer 2

True- the same mutation can cause different signs and symptoms in different people

Question 3

True or False- Retinal Dystrophies can either affect the full retina or just the macula

Answer 3

True

Question 4

What are some examples of full retinal dystrophies?

Answer 4

Retinitis Pigmentosa (RP)

Leber’s Congenital Amaurosis (LCA)

Congenital Stationary Night Blindness (CSNB)

Question 5

What are some examples of Macula retinal dystrophies?

Answer 5

Bests Vitelliform

Juvenile X-linked retinoschisis

Autosomal dominant drusen

Stargardt Fundus Flavaimaculatus

Sorsby Disease

Question 6

What are the possible causes of Retinitis Pigmentosa (RP)?

Answer 6

–Autosomal Dominant RP

–Autosomal Recessive RP

–X-linked RP

-Sporadic mutation

Question 7

What is Retinitis Pigmentosa (RP)?

Answer 7

• A Heterogeneous group of retinal disorders
• It is a Rod-cone dystrophy

–Progressive dysfunction of rods, then subsequently the cone photoreceptors and RPE occurs.

It is due to the mutation of the rhodopsin gene.

Question 8

What are signs of Retinitis Pigmentosa?

Answer 8

1.Pigmentation

–Bone-spicule and pigment clumping in mid-perphery of fundus

–This can be Hypo- or hyper- pigmentation of RPE

2. Thinning/attenuation of blood vessels
3. Pale waxy disk

Question 9

Is Retintis Pigmentosa bilateral or unilateral?

Answer 9

Biateral although one eye tends to progress faster than the other

Question 10

What conditions is Retintis Pigmentosa (RP) associated with?

Answer 10

• PSC cataracts
• CMO
• Myopia and astigmatism

Question 11

What are symptoms of Retintis Pigmentosa?

Answer 11

• Nactylopia (night blindness) - this is the first symptom and is due to rod loss (as shortening of rod receptor occurs due to phagocytosis)
• Progressive loss of peripheral vision – noticed later on

–Tunnel vision

Question 12

What is sectoral Retintis Pigmentosa (RP)?

Answer 12

When signs of Retintis Pigmentosa i.e. that bone spicule pigment clumping exists in one particular quatre of the retina.

Question 13

What do we have to be careful not to confuse Retintis Pigmentosa with and why?

Answer 13

We don’t want to confuse Retintis Pigmentosa with Albipuntcatis (which is a form of congenital stationary night blindness) as the prognosis is different.

Both conditions present with nightblindness as a symptom.

Question 14

How do we diagnose Retinitis Pigmentosa (RP)?

Answer 14

Take a thorough family history to check for inheritance likelyhood.

Full field ERG- rods should behave abnormally ( as seen in the picture highlighted by the yellow circle in comparison to the normal row below)

Test the px’s dark adaptation - RP px cannot dark adapt (as well) - compare the red line to the blue normal line in the graph.

Visual fields - later on RP px develop scotomas which join to form a mid periphery ring scotoma which constricts to form tunnel vision

Question 15

What is the likelyhood of passing on Autosomal dominant RP to offspring and is it more likely in males or females?

Answer 15

50% risk of passing on to offspring

Equally as common in males and females

Question 16

What is the cause of Autosomal Dominant RP?

Answer 16

• Single gene mutation.
• However ~30 causative genes have been identified. Rhodopsin gene (RHO) most common one.

[It is responsible for 15-20% of all RP cases in the UK]

Question 17

How is autosomal recessive RP passed on (i.e. under what conditions does the offspring express RP)?

Answer 17

Both parents must have the gene for it in order for it to be expressed in offspring.

Question 18

What is the cause of Autosomal recessive RP?

Answer 18

•Can be mutation in genes including RHO gene, gene encoding alpha or beta subunit of cGMP phosphodiesterase, or the alpha subunit of the cGMP gated channel.

Question 19

What is the cause of x linked RP?

Answer 19

•Most cases (70%) due to a mutation in RGPR gene on the X-chromosome

Question 20

In what gender is X linked RP more commonly expressed?

Answer 20

Males - females tend to just be carriers.

Question 21

Which form of RP is the most severe and why?

Answer 21

X linked RP as:

–Childhood onset night blindness occurs from 1st decade

–Px experiences Poor central vision

–Myopia

Question 22

Why are women less affected by X linked RP?

Answer 22

• Women have two X chromosomes and a normal copy on the one X chromosome can partially compensate for a pathological variant on the other X chromosome.
• Female carriers have variable expression.

Question 23

How can one identify a female carrier of X linke RP from their fundus?

Answer 23

They show a tapetal reflex that is specific is RP carriers

Question 24

What are systemic associations of RP like dystrophies?

Answer 24

Syndromes such as:

• Usher’s syndrome (serious hearing loss; 18% of all RP)
• Kearns-Sayre syndrome (external ophthalmoplegia, lid ptosis, heart block)
• Bardet-Biedl syndrome (polydactyl - i.e. extra fingers and toes, truncal obesity, short stature)

Question 25

What is Leber’s Congenital Amaurosis (LCA)?

Answer 25

•An Autosomal recessive condition in which there is an abnormal development of photoreceptor cells

Question 26

What is the rate of progression and prognosis like in Leber’s Congenital Amaurosis (LCA)?

Answer 26

Rate of progression is poor but the prognosis is ultimately poor

Question 27

What is the prevalence of Leber’s Congenital Amaurosis (LCA)?

Answer 27

•Prevalence ~3 in 100,000

Question 28

How many different forms of Leber's Congenital Amaurousis (LCA) is there?

Answer 28

At least 20 different forms of LCA, each caused by a defect in a different gene important for normal visual function

Question 29

What is the most common form of inherited sight loss in children?

Answer 29

Leber’s Congenital Amaurosis (LCA)

Question 30

What associations does Leber’s Congenital Amaurosis (LCA) have?

Answer 30

* Can be associated with cataract/keratonoconus * Can have systemic associations e.g. abnormal kidney function/defects

Question 31

What are symptoms of Leber’s Congenital Amaurosis (LCA) and how may it ultimately be confirmed?

Answer 31

* Parents may notice lack of visual responsiveness, nystagmus, tropia, oculodigital reflex (children press on eyes) * Nyctalopia from birth * Photophobia * Decreased VF from 1 yr * VA ~ 6/36 * May be associated with high hyperopia or myopia * Confirmed with genetic test

Question 32

What would be seen on an ERG of a px with Leber's Congenital Amaurosis (LCA)?

Answer 32

Abnormal ERG - signifcantly reduced photopic and scotopic response

Question 33

How may the fundus of a px with Leber's Congenital Amaurosis (LCA) present?

Answer 33

Fundus may appear normal May have slight Blood vessel attnetuation May have subtle RPE granularity

Question 34

Is Congenital Stationary Night Blindness (CSNB) a progressive condition?

Answer 34

No

Question 35

What are common symptoms of Congenital Stationary Night Blindness (CSNB)?

Answer 35

•High myopia at a young age, nystagmus, reduced VA and strabismus are common (especially when X-linked inheritance is the cause).

Question 36

What does the degree of night blindness in Congential Stationary Night Blindness depend on?

Answer 36

•Dysfunction depends on mutation. - thus sometimes it can be mild and in other cases it can be severe

Question 37

How do we diagnosis Congenital Stationary Night Blindness?

Answer 37

•Diagnosis is by ophthalmological appearance, family history, genetic testing and use of an electroretinogram.

Question 38

True or False- Congenital Stationary Night Blindness is a group of diseases

Answer 38

True

Question 39

How can Stationary night blindness be classifed?

Answer 39

By cause. By fundus appearance By mode of inheritance By specific of ERG By gene affected [Then subclassified By whether it is complete or incomplete]

Question 40

What is the difference between complete and incomplete CSNB?

Answer 40

Complete CSNB= complete absence of rod function Incomplete CSNB = rod ERG reduced

Question 41

How does the ERG of a normal px differ to that of a px with CSNB (both complete and incomplete)?

Answer 41

Question 42

What is Fundus Albipunctatus and what does it result in?

Answer 42

It is an Autosomal recessive condition that affects rod and cone photopigment kinetics It leads to Grossly extended dark adaptation times however eventually normal thresholds are reached. ERGs and EOGs eventually normal, but only after prolonged period of adaptation prior to testing.

Question 43

How does Fundus Albipunctatus present appearance wise?

Answer 43

Lots of dull white spots on the retina

Question 44

**_Oguchi’s Disease_** What type of disease is this? How does the fundus appear? What kind of abnormality is this? Can the retina dark adapt?

Answer 44

It is a type of congenital stationary night blindness - it is a Rare autosomal recessive disease. Fundus looks grey/yellow metallic (but appears normal after prolonged dark adaptation). Post-receptoral abnormality (i.e. its not an abnormality of the photoreceptor but processing further down the line) (Regeneration of the pigment is normal) Cone adaptation normal, rod adaptation grossly delayed (2-24 hours). Eventually normal thresholds.

Question 45

* What type of inheritance does retinitis pigmentosa follow? * A) Autosomal recessive * B) Autosomal dominant * C) X-linked recessive * D) Any of the above

Answer 45

D

Question 46

* What kind of fundus appearance might you see in someone with LCA? * A) Normal * B) Bone spicule * C) Tapetal reflex * D) RPE granularity

Answer 46

D) RPE granularity

Question 47

* Low vision, squint and myopia are most associated with which form of CSNB? * A) Autosomal recessive * B) Autosomal dominant * C) X-linked recessive D) CSNB with abnormal fundus appearance

Answer 47

C) X linked Recessive

Question 48

What is the difference between a dystrophy and a degeneration?

Answer 48

A dystrophy is purely inherited, usually as a result of a single gene mutation. Degenerations are age-related. There may be certain genetic mutations which predispose towards development (e.g. CFH mutations in AMD) but onset is usually multifactorial (not purely inherited).