Ocular Abnormality- Hereditary Choroidal & Retinal Dystrophy

Front 1

What is a dystrophy?

Back 1

• Hereditary disorder

• Disruption the function of a particular structure or tissue – Initially normal

Front 2

When is the function of a structure modified?

Back 2

Function modified when abnormal gene switched on

• Abnormal gene modifies one of the metabolic pathways of the tissue,– results in abnormal nutrition and tissue degeneration

Front 3

Where are rare recessive gene diseases more common?

Back 3

In small isolated populations

Front 4

Where/what can a dystrophy affect in relation to the eye?

Back 4

Typically affect the retinal pigment epithelium, photoreceptors or the choriocapillaris

Front 5

When can a dystrophy manifest?

Back 5

early childhood or later life

Front 6

Are dystropies bilateral?

Back 6

Usually bilateral and symmetrical

Front 7

How much of the UK population do eye dystropies affect?

Back 7

• Affect ~1 in 2,000 of the UK population

Front 8

What percentage of all registwred severely sight impaired do dystophies account for?

Back 8

• Account for ~2 % of all registered severely sight-impaired

Front 9

What are dystophies usually associated with?

Back 9

Frequently associated with myopia and cataracts

Front 10

What is autosomal recessive?

Back 10

– Recessive gene carried in first 22 chromosomes

– Both parents need to carry recessive gene

– Both parents carriers if they do no show traits

– Risk factor 25%

– Variable expressivity

– Generally earlier onset and more severe course

Front 11

What is autosomal dominant?

Back 11

– Dominant gene carried in first 22 chromosomes

– Only one parent needs to carry gene

– Gene is dominant

– One parent will be affected

– Risk factor 50%

– Variable expressivity

– Later onset and milder course

Front 12

What investigations should you carry out when presented with a possible hereditary disorder?

Back 12

• Full symptoms & history

– Family history

• Visual acuity

• Pupil reactions

• Visual fields

– Amsler charts

• Colour vision assessment

• Dilated fundus examination

Front 13

Name some common Photoreceptor / RPE cell complex Dystrophies.

Back 13

• Retinitis Pigmentosa (RP) dystrophies

• Leber’s amaurosis

• Stationary night blindness

• Cone dystrophies

Front 14

Name some Retinitis Pigmentosa (RP) dystrophies.

Back 14

– Purely ocular RP

– Usher’s syndrome

– Laurence-Moon Bardet-Biedl syndrome

Front 15

What is Retinitis Pigmentosa?

Back 15

• Progressive loss of photoreceptor (mainly rod) and RPE function

- receptor/RPE cell metabolic complex affected.

• Most common hereditary retinal dystrophy

Front 16

What are the common features of Retinitis Pigmentosa?

Back 16

A group of diseases with the common features

– Pigmentary retinal degeneration

– Nyctalopia (night blindness)

– Visual field defects

Front 17

What is the overall prevalence of Retinitis Pigmentosa?

Back 17

1 in about 5,000

Front 18

What is the percentage of autosomal recessive Retinitis Pigmentosa?

Back 18

Autosomal recessive:

20-75 % – Can be severe

Front 19

What is the percentage of autosomal dominant Retinitis Pigmentosa?

Back 19

Autosomal dominant :

17-43 %

-Least severe

Front 20

What percentage of Retinitis Pigmentosa is x linked recessive?

Back 20

X linked recessive: 8-18 %

Most severe case

Front 21

With x linked recessive Retinitis Pigmentosa, when would you reach blindness?

Back 21

Complete blindness by 3rd to 4th decade

Front 22

With x linked recessive Retinitis Pigmentosa, What do female carriers show?

Back 22

Retinal signs

Front 23

What percentage of Ocular Retinitis Pigmentosa is sporadic cases?

Back 23

23%

Front 24

How long do sporadic cases retain central vision?

Back 24

Into 6th decade

Front 25

What are the symptoms Retinitis Pigmentosa?

Back 25

• Night blindness

• Slow dark adaptation

• Reduced peripheral field

• Photopsia

• Central visual loss late feature

– Loss of cones

– But cataract may affect it earlier

Front 26

What are the signs of Retinitis Pigmentosa?

Back 26

• Loss of contrast sensitivity – 1st

• Visual acuity normal

• Bilateral intraretinal mid-peripheral pigmentary changes

• RPE atrophy

• Tesselated fundus

• Arterial attenuation

• Optic disc pallor

• Atrophy at the macula

• Epiretinal membrane

• Cystoid macula oedema

Front 27

What is seen at the macula of a female carrier of Retinitis Pigmentosa?

Back 27

Tapetal sheen

Front 28

What is the visual field defect with Retinitis Pigmentosa?

Back 28

Progressive field defect

– Partial or complete ring scotoma ~40-50°

– Concentric reduction

– Central island of vision

• May be lost as well

•Nyctalopia

Front 29

What would happen to the colour vision of Retinitis Pigmentosa?

Back 29

– Acquired type 3 (tritan) colour deficiency

Front 30

Around what age would X-linked R.P. be diagnosed?

Back 30

~4 years old in predisposed families, otherwise found by routine eye examination

Might see a ring scotoma

Front 31

What would be seen in the 1st Decade (0-10 years) of an X-linked R.P.?

Back 31

– Granular appearance of equatorial RPE

– Retinal blood vessel attenuation

– Temporal optic atrophy

• First symptom usually night blindness

Front 32

What would be seen in the 2nd Decade (11-20 yrs) of a X-linked R.P. px?

Back 32

– Obvious RPE “bone corpuscle” clumps and RPE atrophy

– Vascular attenuation

– Progressive optic atrophy

– Loss of some large blood vessels

Front 33

What are the symptoms in the 2nd Decade (11-20 yrs) of a X-linked R.P. px?

Back 33

• Severe night blindness

• photophopia

•mobility problems due to constricted field

•↓ VA

Front 34

What would be seen the 3rd Decade of a X-linked R.P. px?

Back 34

– Pigment deposits at the posterior pole and throughout the retina

– Optic disc has waxy pallor

– Glassy macular reflex

– Loss of large and small blood vessels

– Unmasking of choroidal blood vessels

– Posterior subcapsular cataract?

– VA reduced to 6/36 - 6/60

– Tubular fields approximately 10 degrees

Front 35

What would be seen the 4th Decade of a X-linked R.P. px?

Back 35

– Severe retinal and choroidal atrophy

– Severe atrerial attenuation

– VA: CF or LP

• Macula

– Atrophic

– Epiretinal membrane

– CMO

– Possible nystagmus

– Cataract in 35%

Front 36

What are the ocular associations with Retinitis Pigmentosa?

Back 36

• Posterior sub-capsular cataract

• Open-angle glaucoma

• Myopia

• Keratoconus

• Vitreous changes

– PVD

– Uveitis

• Optic disc drusen

Front 37

What is Usher’s Syndrome?

Back 37

Deafness and Visual Impairment

Front 38

What is the prevalence of Usher’s Syndrome?

Back 38

Overall prevalence 6.2 in 100,000 in UK population over 15 years

Front 39

What percentage of the young deaf population does ushers syndrome account for?

Back 39

3-6% of young deaf population

Front 40

Describe Type 1 Usher’s Syndrome?

Back 40

Most severe form – 75 % Autosomal recessive, profound congenital deafness, severe RP in first year

Front 41

Describe Type 2 Usher’s Syndrome?

Back 41

– 13 % Autosomal dominant

Front 42

Describe Type 3 Usher’s Syndrome?

Back 42

– 2 % Mild, late onset in the 3rd decade

Front 43

Clinical Course of Usher’s Syndrome

Back 43

Front 44

What is Bardet-Biedl Syndrome(Laurence Moon)?

Back 44

• Retinitis pigentosa combined with

– Polydactly

– Severe learning difficulties

– Bull’s eye maculopathy

– 80% have severe retinal changes by the age of 20 years

Front 45

What is Leber’s Congenital Amaurosis?

Back 45

• The earliest and most severe retinal dystrophy resulting in blindness in infancy.

First reported in 1869

Front 46

How is Leber’s Congenital Amaurosis aquired?

Back 46

Inheritance : Autosomal recessive

Front 47

State the prevalence of Leber’s Congenital Amaurosis?

Back 47

• 3 in 100,000

• 10-20 % of child blindness, 5% of all inherited eye disease

Front 48

What are the clinical findings of Leber’s Congenital Amaurosis?

Back 48

• Peripheral pigment stippling

• Vessel attenuation

• Hypoplastic disc

• Wrinkled internal limiting membrane

Front 49

What does Leber’s Congenital Amaurosis lead to?

Back 49

• Leads to depigmentation, diffuse atrophy, multifocal pigmentary lesions at the posterior pole.

• Pupillary light reflex absent

Front 50

What are the two clinical forms of Leber’s Congenital Amaurosis?

Back 50

• Congenital or complicated

• Juvenile or Uncomplicated

Front 51

Describe the Congenital or complicated form of Leber’s Congenital Amaurosis?

Back 51

– Visual impairment at 3 - 5 months

– Photophobia, nystagmus

– Poor pupil responses

– Blindness in 1st year

– Often fatal due to systemic complications

Front 52

Describe the Juvenile or Uncomplicated form of Leber’s Congenital Amaurosis?

Back 52

– Poor vision falling to 6/60 with nystagmus at 10 years – Hypermetropia and cataract in 50% – Retina initially normal - similar to RP by ~3yrs

Front 53

What are the signs and symptoms of cone dystrophy?

Back 53

– Poor VA, photophobia, poor colour vision and nystagmus

Front 54

What are the characteristics of cone dystophies?

Back 54

Characteristic “Bull’s eye” maculopathy. – Hyperpigmentation surrounded by rings of hypo and hyper

Front 55

What is Batten’s Disease?

Back 55

• A cone dystrophy

• The most common neurodegenerative disease in children and young adults worldwide

• Neurolipidosis – can be fatal

Front 56

What happens with Batten’s Disease?

Back 56

Lipopigments accumulate in neural, visceral and somatic tissue resulting in seizures, psychomotor deterioration and blindness

Front 57

Describe the Infantile type of Batten’s Disease.

Back 57

• Onset before 2 years

– Rapid progressive psychomotor disorder

– Abnormal gene on chromosome 1

– VA initially good

Front 58

Describe the Late infantile type of Batten’s Disease.

Back 58

• Onset 2-6 years

– Abnormal genes on chromosome 11 or 15

– VA initially good

Front 59

Describe the Juvenile type of Batten’s Disease.

Back 59

• Onset 4-6 years

– Typical “Bull’s Eye” macula. Poor VA

– Widespread atrophy of the RPE

– Progressive mental retardation

– Death in 3rd decade

– Abnormal gene on chromosome 16

Front 60

Describe the Adult (Kuf’s disease) type of Batten’s Disease.

Back 60

– Pre-senile dementia

– Mild “bull’s eye” macula. VA slightly affected

Front 61

Name some Retinal Pigment Epithelial Dystrophies.

Back 61

• Stargardt’s disease complex (fundus flavimaculatus).

• Vitelliform dystrophies (Best disease).

• Familial dominant drusen.

Front 62

What is Stargardt’s disease?

Back 62

The disease causes progressive damage or degeneration of the macula.

Front 63

State the prevalence of Stargardt’s disease.

Back 63

Prevalence : 1 in 10,000

Front 64

How is Stargardt’s Disease aquired?

Back 64

Autosomal recessive (or dominant)

Front 65

What are the common features of Stargardt’s disease?

Back 65

• Yellow, concentric, sub-retinal flecks which stain with fluorescein

– Similar to drusen but triangular

• Macular atrophy common

– Reduced visual acuity

Front 66

Whatis the clinical course of Stargardt’s disease?

Back 66

• Onset in the 2nd decade

• Pigmentary macular degeneration

• Peripheral subretinal flecks

- enlarged RPE cells filled with lipofuscin-like material

• Progressive diffuse atrophy of the RPE

Front 67

What is the colour visual function of Stargardt’s disease?

Back 67

• Colour vision : early onset of Type 1 red / green acquired deficiency similar to a congenital protan.

Front 68

What is the Visual acuity like with Stargardt’s disease?

Back 68

– Reduced in the 2nd decade

– Severe progressive loss of VA

- CF in the 4th decade.

Front 69

What would be seen on a visual fields plot with Stargardt’s Disease?

Back 69

central scotoma

Front 70

What appears with Familial Dominant Drusen?

Back 70

Drusen appear 2nd-3rd decades around macula and optic disc

Front 71

What is the visual function like with Familial Dominant Drusen?

Back 71

• Normal

• Minority develop early ARMD

Front 72

What is Best Vitelliform Macular Dystrophy?

Back 72

An autosomal dominant genetic form of macular degeneration that usually begins in childhood or adolescence and slowly progresses to affect central vision.

Front 73

What would be seen at the macula with Best Vitelliform Macular Dystrophy?

Back 73

• Accumulation of yellow material beneath retina and RPE (esp.macula)

• Occurs between 4 – 10 years of age

• “Egg yoke” pattern at macula

Front 74

How is the vision affected with Best Vitelliform Macular Dystrophy?

Back 74

– Hyperopic shift (subjective) – Asymptomatic or slightly reduced VA

Front 75

What happens in the 2nd-4th decade of Best Vitelliform Macular Dystrophy?

Back 75

• Cyst collapses in

– Material reabsorbed by the RPE giving pseudohypopyon then “scrambled egg” appearance

Front 76

What is the end stage of Best Vitelliform Macular Dystrophy?

Back 76

Atrophy of the RPE and disciform degeneration finally result with profound loss of VA.