DIS - Inherited Retinal Disease - Week 2

Question 1

What are most genetic diseases and how is AMD different to them?

Answer 1

Many inherited retinal diseases are monogenic

AMD involves multiple genes, environmental factors, dietary factors, and lifestyle habits

Question 2

Can the exact same mutations in one gene cause different disease presentations or do they always have the same outcome?

Answer 2

Can cause different presentations

-epistasis

Question 3

Define epistasis.

Answer 3

A form of gene-gene interaction in which genes not directly involved in causing the disease have an effect on the phenotypic expression of the disease trait (caused by the mutation in another gene)

Question 4

What are rod-cone dystrophies?

Answer 4

A family of progressive diseases in which rod dysfunction is more severe than cone dysfunction

Question 5

Can rod-cone dystrophies cause night blindness?

Answer 5

Yes

Question 6

What kind of vision loss do rod-cone dystrophies cause?

Answer 6

Peripheral loss

Question 7

Describe the severity and progression of rod-cone dystrophies at birth or if developed in childhood.

Answer 7

Severe at birth, with little progression
Can be developed in childhood with rapid progression
-usually results in severe vision loss and nystagmus

Question 8

Describe how delayed onset rod-cone dystrophies differ from early onset. Do they result in complete vision loss or nystagmus?

Answer 8

Symptoms develop late and progress more slowly

Rarely results in near complete vision loss or nystagmus

Question 9

What kind of disease is lebers congenital amaurosis and what kind of mode of inheritance does it have? Is it common or rare?

Answer 9

Common form of early onset rod-cone dystropy

Autosomal recessive

Question 10

What kind of vision is present since birth for those with lebers congenital amourosis? What else is present?

Answer 10

Very poor vision with roving nystagmus

Question 11

What is the fundus like in lebers congenital amourosis?

Answer 11

May appear normal or may show abnormalities

Question 12

Is ERG normal or abnormal with lebers congenital amourosis?

Answer 12

Abnormal

Question 13

Is x-linked retinitis pigmentosa a common or uncommon form of retinitis pigmentosa? What about rod-cone dystrophy?

Answer 13

Common form of early onset rod-cone dystrophy, but not a common form of RP overall

Question 14

Which gender is usually fully affected with x-linked retinitis pigmentosa? Explain.

Answer 14

Males usually fully affected

Females often have milder form (can be fully affected)

Question 15

What is vision like in childhood with x-linked retinitis pigmentosa? What eventually happens?

Answer 15

Fairly good vision in childhood, but lose both peripheral and central vision rapidly

Question 16

How many genes have been implicated in x-linked retinitis pigmentosa?

Answer 16

At least 6

Question 17

What is the most common form of retinitis pigmentosa?

Answer 17

Autosomal recessive

Question 18

List three classical features of retinitis pigmentosa.

Answer 18

Night blindness
Loss of peripheral vision
Intraretinal pigmentation
-bone spicule-like

Question 19

Are the dominant or recessive forms of retinitis pigmentosa often more severe?

Answer 19

Recessive forms often more severe

Question 20

How many genes are implicated in autosomal recessive retinitis pigmentosa?

Answer 20

At least 25

Question 21

What is the second-most common form of retinitis pigmentosa?

Answer 21

Autosomal dominant

Question 22

Does autosomal dominant retinitis pigmentosa have the classical features of retinitis pigmentosa?

Answer 22

Yes

Question 23

Describe the severity, age of onset, and penetrance of autosomal dominant retinitis pigmentosa (2).

Answer 23

It varies widely depending on abnormal function gained and haploinsufficiency

Question 24

Is it easy or difficult to predict causal gene from the observed phenotype in autosomal dominant retinitis pigmentosa?

Answer 24

Difficult

Question 25

How many genes are implicated in autosomal dominant retinitis pigmentosa?

Answer 25

At least 18

Question 26

Describe cone-rod dystrophies.

Answer 26

Family of progressive diseases in which cone dysfunction is more severe than rod dysfunction

Question 27

What kind of vision loss is expected in cone-rod dystrophies?

Answer 27

Loss of central vision - central scotoma

Question 28

What is seen on ERG with cone-rod dystrophies?

Answer 28

Cone-driven ERG responses affected

Question 29

Is retinal damage typically seen with cone-rod dystrophies?

Answer 29

Yes | -atrophy and/or pigmentary changes

Question 30

True or false Cone dystrophies are allelic to cone-rod dystrophies Explain what this means.

Answer 30

True Cone and cone-rod dystrophies represent phenotypic variations of the same disease

Question 31

True or false | Cone and cone-rod dystrophies do not cause light aversion.

Answer 31

False | They do

Question 32

How many genes are implicated for the following cone and cone-rod dystrophies? X-linked Autosomal recessive Autosomal dominant

Answer 32

X-linked - at least 1 Autosomal recessive - at least 13 Autosomal dominant - at least 13

Question 33

What are vitreoretinal dystrophies?

Answer 33

Retinal disorders associated with vitreal degeneration

Question 34

What is one of the most common causes of macular disease in male children? Especially what ethnicity?

Answer 34

X-linked retinoschisis | -finnish

Question 35

What would yuo expect to see on an ERG with retinoschisis (2)?

Answer 35

Selective reduction in b-wave of DA-white ERG | -reduced b/a-wave ratio

Question 36

What does enhanced S-cone syndrome cause and what mode of inheritence? Does it cause vision loss? What about night vision and at what age? What happens to the other cones?

Answer 36

Gain in function of s-cones Causes visual loss with night blindness from early age Varying degree of L and G cone vision and retinal degeneration

Question 37

What happens to the retina with enhanced S-cone syndrome and what area?

Answer 37

Abnormally thick retina in annulus surrounding the fovea

Question 38

What is the severe form of enhanced S-cone syndrome called and what is it similar to?

Answer 38

Goldmann-favre vitreoretinal dystrophy | -similar to clumped pigmentary retinal degeneration

Question 39

What can enhanced S-cone syndrome mimic?

Answer 39

X-linked retinoschisis

Question 40

What would you expect to see on ERG with enhanced S-cone syndrome (2)?

Answer 40

Both DA white and LA white ERG responses are usually electronegative

Question 41

How many genes are implicated in enhanced S-cone syndrome?

Answer 41

1

Question 42

What mode of inheritence do the following have: Sticker syndrome Wagner syndrome

Answer 42

Both autosomal dominant

Question 43

What are exudative vitreoretinopathies (3)?

Answer 43

Predisposition to retinal exudates Leaky angiography Predisposition to seous retinal detachments

Question 44

Is it common or rare to lose all vision in retinitis pigmentosa?

Answer 44

Rare

Question 45

Describe retinitis pigmentosa and dark adaptation and night blindness.

Answer 45

Those with RP have difficulty with dark adaptation and night blindness during adolescence

Question 46

Describe the progression of vision loss over time with retinitis pigmentosa (3).

Answer 46

Lose mid-peripheral vision, then far peripheral vision in adulthood Eventually tunnel vision -reductions in central vision occur later

Question 47

Are the signs and symptoms of retinitis pigmentosa consistent or highly variable?

Answer 47

Highly variable

Question 48

What three things can you expect to see in advanced cases of retinitis pigmentosa?

Answer 48

Intraretinal bone spicule pigmentation in the midperiphery Waxy pallor of the optic disc Attenuated retinal blood vessels

Question 49

Why do bony spicule pigmentation occur where they do in retinitis pigmentosa?

Answer 49

In the midperiphery because this is the region of greatest rod density

Question 50

What five things may you see in early cases of retinitis pigmentosa?

Answer 50

``` Night blindness Loss of peripheral vision Difficulty with tasks requiring good VA Myopia/astigmatism Hearing loss ```

Question 51

Define nyctalopia.

Answer 51

Night blindness

Question 52

What is the progression of night blindness like in retinitis pigmentosa and when is it typically first noticed?

Answer 52

Often slow and insidious onset/progression | First noticed 2nd or 3rd decade

Question 53

What percentage of retinitis pigmentosa patients will develop cystoid macula oedema, if any?

Answer 53

10%

Question 54

What will most retinitis pigmentosa patients develop in adulthood?

Answer 54

Posterior subcapsular cataract

Question 55

Is hearing loss common or rare in retinitis pigmentosa patients?

Answer 55

Common

Question 56

List the nine components of assessing retinitis pigmentosa.

Answer 56

``` VA Refraction Visual fields Colour vision Dark adaptation Slit lamp Ophthalmoscopy ERG OCT ```

Question 57

What would you expect of VA when assessing retinitis pigmentosa? What about early cases?

Answer 57

Can remain normal | -can be lost early

Question 58

What is myopia with retinitis pigmentosa more indicative of? What about hypelopia?

Answer 58

Myopia greater than -2.00D - more likely to be X-linked | Hyperopia - more likely to be autosomal dominant

Question 59

What kind of visual field defects would you expect when assessing retinitis pigmentosa?

Answer 59

Mid-peripheral scotomas early, which expand outward and inward

Question 60

Describe the progression of visual field defects over time in retinitis pigmentosa towards the pole and towards the periphery.

Answer 60

Mid-peripheral scotomas early - central margin is steeper and progresses slowly - peripheral margin is flatter and progresses rapidly

Question 61

Are defects often symmetrical or asemmetrical in retinitis pigmentosa?

Answer 61

Symmetrical

Question 62

What may retinitis pigmentosa visual field defects mimic? What two things should it not be confused with?

Answer 62

Arcuate defect | -dont confuse with glaucoma or ONH drusen

Question 63

When should central field testing be done for retinitis pigmentosa cases, if at all?

Answer 63

Late stage

Question 64

What is expected of colour vision in retinitis pigmentosa? What may other abnormalities indicate?

Answer 64

Normal (early) or acquired tritanopia (late) | -other abnormalities may indicate cone or cone-rod dystrophy

Question 65

What may you find on slit lamp examination of a retinitis pigmentosa patient?

Answer 65

Posterior sub-capsular cataract

Question 66

What may commonly be seen in the vitreous humour of retinitis pigmentosa patients?

Answer 66

Cells

Question 67

Why should you do OCT for retinitis pigmentosa (2)?

Answer 67

Assess the status of the photoreceptor layer (ISe integtrity) Identify presence/absence of CMO

Question 68

List 6 other syndromes that are differential diagnoses for retinitis pigmentosa.

Answer 68

``` Usher Bardet-biedl Alport Cohen Jeune Cockayne ```

Question 69

List four conditions that mimic retinitis pigmentosa.

Answer 69

Syphillis Measles Trauma Drug toxicities

Question 70

What drug toxicity can mimic retinitis pigmentosa?

Answer 70

Quinine/chloroquine

Question 71

List three conditions that cause RPE disruptions that are differential diagnoses for retinitis pigmentosa.

Answer 71

Old retinal detachment Choroideremia Gyrate atrophy

Question 72

What four referrals may cases of retinitis pigmentosa require?

Answer 72

Ohpthalmological examination Electrodiagnosis (ERG) Dark adaptationGenetic counselling

Question 73

What five baselines should be maintained for retinitis pigmentosa patients?

Answer 73

``` VA Colour vision Visual fields Retinal photography Dark adaptation ```

Question 74

List 5 vision rehabilitation options for retinitis pigmentosa patients.

Answer 74

``` Tinting Night vision goggles Wide angle mobility lamp Field expanders Hand-held/computer assisted magnifiers ```

Question 75

Which of the following treatment options are effective for retinitis pigmentosa: Vitamin/minerals, vasodilators, tissue therapy with placental extract, cortisone, cervical sympathectomy, injections of a hydrolysate of yeast ribonucleic acid (RNA), ultrasound, transfer factor, dimethyl sulfoxide (DMSO), ozone, muscle transplants, and subretinal injections of foetal retinal cells.

Answer 75

None of these have been proven

Question 76

What is the effect of vitamin A supplementation on retinitis pigmentosa ERG? What about VA and visual fields?

Answer 76

Slows decline in ERG amplitude | VA and visual fields not significantly affected

Question 77

List two risks of taking high dose vitamin A.

Answer 77

``` Hip fractures Birth defects (not recommended for pregnant women) ```

Question 78

What is the effect of vitamin A supplementation on retinitis pigmentosa patients?

Answer 78

No clear benefit

Question 79

Does light exposure in retinitis pigmentosa speed up degeneration? Explain.

Answer 79

In animals yes | In humans, there was no effect

Question 80

List 4 possible future treatment options for retinitis pigmentosa.

Answer 80

Gene therapy Nutritional/neuroprotective intervention Transplantation (stem cells) Implants