Unit 6 - Inherited retinal disease Flashcards
How common are inherited retinal diseases?
1 in 3000
As a cause of SSI how important is inherited retinal disease?
Leading cause in adults and second in kids
When suspecting inherited retinal disease what questions should we ask?
- Central/peripheral
- Bilateral/symmetrical
- Day or night
- Family history
- Medical history
Why do we bother gene testing?
To prove it is genetic
To give an idea of risk to kids
To see if treatable RPE65
What is optogenetics?
Making other neurons light sensitive i.e. bipolar cells
In Best’s disease what signs would you see?
Yellow deposit at macula
What vision would you expect in Best’s?
Pretty normal until middle age then vision declines
What is the cause of BEST’s disease?
Lipofuscin accumulation in RPE leading to photoreceptor destruction?
What is the genetic cause of BEST’s disease?
BEST1 missense mutation. BEST 1 modulates calcium channel function.
What sort of inheritance pattern does most BEST follow?
AD
What are the stages of BESTs disease?
0,normal fundus (abnormal EOG)
I - minor RPE changes
II - typical vitelliform lesion
IIa - scrambled egg appearance (v/a often deteriorates at this stage)
III - pseudohypopyon phase
IVa - atrophic RPE
IVb - fibrous scar tissue
IVc - CNVM
What would you expect in electrophysiology testing in BEST’s?
Reduced EOG
Normal ERG
What would a FAF look like in BESTs?
Yellowish material is intensely hyperautofluorescent becomes hypo went atrophy occurs
What would an FFA look like in BESTs?
Hypofluorescent due to masking
How common is BESTs?
Second commonest inherited retinal disease
What signs would you get in Stargadt’s disease?
Fundus mottling
Yellow-white flecks in RPE
Peripheral RP like pigmentation
What would electrophysiology be like in Stargardt’s?
Abnormal pattern ERG
Full field ERG variable
EOG may also be abnormal
What is the genetic cause of Stargardt’s?
ABCA4 mutation leads to defective transporter protein responsible for removal of all-trans retinal from OS disc
What sort of inheritance is Stargardt’s?
AR but carrier rate is as high as 1 in 50
What is the treatment of Stargardt’s?
Avoidance of excessive light, vitamin A supplementation
What future treatments of Stargardt’s are being considered?
Gene replacement therapy
Tissue replacement
Pharmacological agents to slow the visual cycle
What does the FFA and FAF look like in Stargardt’s?
FFA - dark choroid due to masking of choroidal fluorescence
FAF distinc pattern of hyperreflective flecks and dark central atrophy
How does atrophy occur in Stargardt’s?
Photoreceptor loss is secondary to build up of lipofuscin and A2E in RPE.
Which patients are affected with X-linked retinoschisis?
Men only - x linked
What would the electrodiagnostics look like the x-linked retinoschisis?
Electronegative full field ERG - b wave smaller than a wave
Which gene is affected in x-linked retinoschisis?
RS1
What treatment may help x-linked retinoschisis?
Carbonic anhydrase inhibitors
Vitrectomy for RD or VH
Gene therapy has worked in mouse model
What is the appearance of x-linked retinoschisis?
Whitish drusen-like dots and pigment variaion
What % of x- linked retinoschisis patients will have peripheral retinal changes?
50%
What does the RS1 gene do?
Loosens adhesion between cells allowing fluid accumulation
What other ocular signs are associated with X-linked retinoschisis?
Amblyopia
Strabismus
What is inheritance pattern in Doyne honeycomb choroiditis?
AD - dominant drusen
What is different about drusen in dominant drusen?
Around disc
Symmetrical
What gene is responsible for dominant drusen?
EFEMP1
