Hereditary Dystrophies

Question 1

Classification of hereditary dystrophies?

Answer 1

• LOCATION:
  o Generalised:
   Rod-cone dystrophy – can affect whole of retina in varying degree depending on which is predominant feature affected
   Cone-rod dystrophy – can affect whole of retina in varying degree depending on which is predominant feature affected
  o Central:
   Macula only
• PROGRESSION:
  o Stationary – non-progressive – detect in child and doesn’t get worse
  o Progressive – nature of majority
• PATHOLOGICAL FOCUS:
  o Photoreceptors
  o RPE
  o Choroid

Question 2

Systemic associations of Retinitis Pigmentosa?

Answer 2

• ~25% associated with systemic disease
• Usher’s syndrome – condition where have retinitis pigmentosa with deafness
• Barder-Biedl syndrome – blindness and deafness as well as polydactyly (extra fingers)
• Kearns-Sayre syndrome – rare neuromuscular disorder – have weakness/paralysis of eye muscles, impairs eye movement and causes ptosis
• Refsum disease – rare disease causes weakness or numbness of hands and feet (peripheral neuropathy) – retinitis pigmentosa in eye
• Mucopolysaccharidosis – body missing or does not have enough of enzyme needed to break down long chains of sugar molecules – opacity/clouding develops in cornea, optic disc swelling, optic nerve atrophy

Question 3

Symptoms of retinitis pigmentosa?

Answer 3

• Nyctalopia – reduced night vision
• Reduced VF
• Reduced VA – later stages – detect pxs in childhood/teenage years – gradual onset so px may not be aware of

Question 4

Signs of RP?

Answer 4

• Mid peripheral bony spicules – pigmented areas
• Pale disc – ‘waxy pallor’
• Arteriolar attenuation
• Cataract
• Myopia
• POAG
• CMO

Question 5

What is the classic triad of signs in RP?

Answer 5

• Pale disc
• Arteriolar attenuation
• Cystoid macular oedema

Question 6

Treatment of RP?

Answer 6

• Supportive
• Low vision assessment
• Blind registration
• Cataract surgery – if significant cataract – can be complicated due to zonular dehisce these pxs can have – would only do if would be some benefit
• Dorzolamide for CMO – carbonic and hydrase inhibitor, is used in glaucoma treatment, not effective in used in all pxs – if doesn’t work then stop using
• Genetic testing:
  o Genetic counselling – get genetic testing, identification of gene involved, gives idea if it is something px could pass on to next generation – some pxs want to know, some don’t or it isn’t relevant e.g. already have children or don’t plan on having any
  o RPE65 gene therapy now available – use viable retinal tissue and reintroduce the correct genes into eye and allow restoration of normal retinal tissue
   Only works if px has RPE65 gene & must have some form of viable retinal tissue

Question 7

What is Stargardt Disease and when does it present?

Answer 7

• Commonest macular dystrophy
• Cone-rod dystrophy – cones predominantly affected, rods can become affected later – start with central loss of vision and eventually lose peripheral field
• ABCA4 gene mutation
• Accumulation of lipofuscin in RPE – stops RPE working way should & stops transfer of nutrients through RPE – breakdown of photoreceptor, RPE & choriocapillaris complex
• Presents in childhood or adolescence
• Progressive condition starting with macula going outwards
• Characterised by retinal flecks

Question 8

How does Stargardt disease appear in the early, moderate and late stages?

Answer 8

Early Stage – just have mottled appearance – doesn’t look abnormal nor completely normal, whiteish orangey lesions in macula
Moderate Stage – accumulation of lipofuscin – yellow areas are the retinal flecks – initially start in para-foveal, para-macular region and can extend outwards
Late Stage – macular becomes atrophic. Atrophic pigmentary changes and atrophic pale macular changes

Question 9

Best Vitelliform Macular Dystophy

Answer 9

• Best’s = juvenile form of disease (different from adult onset vitelliform)
• BEST1 gene mutation
• Involves macula only, not peripheral retina
• Usually bilateral
• Presents in children
• Progressive disease presenting in childhood

Question 10

What are the 5 stages of Best Vitelliform Macular Dystrophy?

Answer 10

1. Pre-vitelliform = electrophysiology changes with normal fundus – rare to pick up at this stage unless have family hx and really looking for it in infant or child
2. Vitelliform lesion = “sunny side up” egg yolk appearance
3. Pseudohypopyon = yellow material settles inferiorly within lesion – fluid level, looks like hypopyon – reset of it will look orangey colour
4. Vitelliruptive = “scrambled egg” appearance – yellowish material starts to break up, starts to looks more bitty
5. Atrophic stage = central atrophy. Risk of secondary CNV – whenever have breakdown of RPE barrier – risk of secondary CNV

Question 11

Best Vitelliform Macular Dystrophy treatment?

Answer 11

Anti-VEGF injections (in child - can get away with just one)