DIS - Inherited Retinal Disease - Week 2 Flashcards
What are most genetic diseases and how is AMD different to them?
Many inherited retinal diseases are monogenic
AMD involves multiple genes, environmental factors, dietary factors, and lifestyle habits
Can the exact same mutations in one gene cause different disease presentations or do they always have the same outcome?
Can cause different presentations
-epistasis
Define epistasis.
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)
What are rod-cone dystrophies?
A family of progressive diseases in which rod dysfunction is more severe than cone dysfunction
Can rod-cone dystrophies cause night blindness?
Yes
What kind of vision loss do rod-cone dystrophies cause?
Peripheral loss
Describe the severity and progression of rod-cone dystrophies at birth or if developed in childhood.
Severe at birth, with little progression
Can be developed in childhood with rapid progression
-usually results in severe vision loss and nystagmus
Describe how delayed onset rod-cone dystrophies differ from early onset. Do they result in complete vision loss or nystagmus?
Symptoms develop late and progress more slowly
Rarely results in near complete vision loss or nystagmus
What kind of disease is lebers congenital amaurosis and what kind of mode of inheritance does it have? Is it common or rare?
Common form of early onset rod-cone dystropy
Autosomal recessive
What kind of vision is present since birth for those with lebers congenital amourosis? What else is present?
Very poor vision with roving nystagmus
What is the fundus like in lebers congenital amourosis?
May appear normal or may show abnormalities
Is ERG normal or abnormal with lebers congenital amourosis?
Abnormal
Is x-linked retinitis pigmentosa a common or uncommon form of retinitis pigmentosa? What about rod-cone dystrophy?
Common form of early onset rod-cone dystrophy, but not a common form of RP overall
Which gender is usually fully affected with x-linked retinitis pigmentosa? Explain.
Males usually fully affected
Females often have milder form (can be fully affected)
What is vision like in childhood with x-linked retinitis pigmentosa? What eventually happens?
Fairly good vision in childhood, but lose both peripheral and central vision rapidly
How many genes have been implicated in x-linked retinitis pigmentosa?
At least 6
What is the most common form of retinitis pigmentosa?
Autosomal recessive
List three classical features of retinitis pigmentosa.
Night blindness
Loss of peripheral vision
Intraretinal pigmentation
-bone spicule-like
Are the dominant or recessive forms of retinitis pigmentosa often more severe?
Recessive forms often more severe
How many genes are implicated in autosomal recessive retinitis pigmentosa?
At least 25
What is the second-most common form of retinitis pigmentosa?
Autosomal dominant
Does autosomal dominant retinitis pigmentosa have the classical features of retinitis pigmentosa?
Yes
Describe the severity, age of onset, and penetrance of autosomal dominant retinitis pigmentosa (2).
It varies widely depending on abnormal function gained and haploinsufficiency
Is it easy or difficult to predict causal gene from the observed phenotype in autosomal dominant retinitis pigmentosa?
Difficult
How many genes are implicated in autosomal dominant retinitis pigmentosa?
At least 18
Describe cone-rod dystrophies.
Family of progressive diseases in which cone dysfunction is more severe than rod dysfunction
What kind of vision loss is expected in cone-rod dystrophies?
Loss of central vision - central scotoma
What is seen on ERG with cone-rod dystrophies?
Cone-driven ERG responses affected
Is retinal damage typically seen with cone-rod dystrophies?
Yes
-atrophy and/or pigmentary changes
True or false
Cone dystrophies are allelic to cone-rod dystrophies
Explain what this means.
True
Cone and cone-rod dystrophies
represent phenotypic variations of the same disease
True or false
Cone and cone-rod dystrophies do not cause light aversion.
False
They do
How many genes are implicated for the following cone and cone-rod dystrophies?
X-linked
Autosomal recessive
Autosomal dominant
X-linked - at least 1
Autosomal recessive - at least 13
Autosomal dominant - at least 13
What are vitreoretinal dystrophies?
Retinal disorders associated with vitreal degeneration
What is one of the most common causes of macular disease in male children? Especially what ethnicity?
X-linked retinoschisis
-finnish
What would yuo expect to see on an ERG with retinoschisis (2)?
Selective reduction in b-wave of DA-white ERG
-reduced b/a-wave ratio
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?
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
What happens to the retina with enhanced S-cone syndrome and what area?
Abnormally thick retina in annulus surrounding the fovea
What is the severe form of enhanced S-cone syndrome called and what is it similar to?
Goldmann-favre vitreoretinal dystrophy
-similar to clumped pigmentary retinal degeneration
What can enhanced S-cone syndrome mimic?
X-linked retinoschisis
What would you expect to see on ERG with enhanced S-cone syndrome (2)?
Both DA white and LA white ERG responses are usually electronegative
How many genes are implicated in enhanced S-cone syndrome?
1
What mode of inheritence do the following have:
Sticker syndrome
Wagner syndrome
Both autosomal dominant
What are exudative vitreoretinopathies (3)?
Predisposition to retinal exudates
Leaky angiography
Predisposition to seous retinal detachments
Is it common or rare to lose all vision in retinitis pigmentosa?
Rare
Describe retinitis pigmentosa and dark adaptation and night blindness.
Those with RP have difficulty with dark adaptation and night blindness during adolescence
Describe the progression of vision loss over time with retinitis pigmentosa (3).
Lose mid-peripheral vision, then far peripheral vision in adulthood
Eventually tunnel vision
-reductions in central vision occur later
Are the signs and symptoms of retinitis pigmentosa consistent or highly variable?
Highly variable
What three things can you expect to see in advanced cases of retinitis pigmentosa?
Intraretinal bone spicule pigmentation in the midperiphery
Waxy pallor of the optic disc
Attenuated retinal blood vessels
Why do bony spicule pigmentation occur where they do in retinitis pigmentosa?
In the midperiphery because this is the region of greatest rod density
What five things may you see in early cases of retinitis pigmentosa?
Night blindness
Loss of peripheral vision
Difficulty with tasks requiring good VA
Myopia/astigmatism
Hearing loss
Define nyctalopia.
Night blindness
What is the progression of night blindness like in retinitis pigmentosa and when is it typically first noticed?
Often slow and insidious onset/progression
First noticed 2nd or 3rd decade
What percentage of retinitis pigmentosa patients will develop cystoid macula oedema, if any?
10%
What will most retinitis pigmentosa patients develop in adulthood?
Posterior subcapsular cataract
Is hearing loss common or rare in retinitis pigmentosa patients?
Common
List the nine components of assessing retinitis pigmentosa.
VA
Refraction
Visual fields
Colour vision
Dark adaptation
Slit lamp
Ophthalmoscopy
ERG
OCT
What would you expect of VA when assessing retinitis pigmentosa? What about early cases?
Can remain normal
-can be lost early
What is myopia with retinitis pigmentosa more indicative of? What about hypelopia?
Myopia greater than -2.00D - more likely to be X-linked
Hyperopia - more likely to be autosomal dominant
What kind of visual field defects would you expect when assessing retinitis pigmentosa?
Mid-peripheral scotomas early, which expand outward and inward
Describe the progression of visual field defects over time in retinitis pigmentosa towards the pole and towards the periphery.
Mid-peripheral scotomas early
-central margin is steeper and progresses slowly
-peripheral margin is flatter and progresses rapidly
Are defects often symmetrical or asemmetrical in retinitis pigmentosa?
Symmetrical
What may retinitis pigmentosa visual field defects mimic? What two things should it not be confused with?
Arcuate defect
-dont confuse with glaucoma or ONH drusen
When should central field testing be done for retinitis pigmentosa cases, if at all?
Late stage
What is expected of colour vision in retinitis pigmentosa? What may other abnormalities indicate?
Normal (early) or acquired tritanopia (late)
-other abnormalities may indicate cone or cone-rod dystrophy
What may you find on slit lamp examination of a retinitis pigmentosa patient?
Posterior sub-capsular cataract
What may commonly be seen in the vitreous humour of retinitis pigmentosa patients?
Cells
Why should you do OCT for retinitis pigmentosa (2)?
Assess the status of the photoreceptor layer (ISe integtrity)
Identify presence/absence of CMO
List 6 other syndromes that are differential diagnoses for retinitis pigmentosa.
Usher
Bardet-biedl
Alport
Cohen
Jeune
Cockayne
List four conditions that mimic retinitis pigmentosa.
Syphillis
Measles
Trauma
Drug toxicities
What drug toxicity can mimic retinitis pigmentosa?
Quinine/chloroquine
List three conditions that cause RPE disruptions that are differential diagnoses for retinitis pigmentosa.
Old retinal detachment
Choroideremia
Gyrate atrophy
What four referrals may cases of retinitis pigmentosa require?
Ohpthalmological examination
Electrodiagnosis (ERG)
Dark adaptationGenetic counselling
What five baselines should be maintained for retinitis pigmentosa patients?
VA
Colour vision
Visual fields
Retinal photography
Dark adaptation
List 5 vision rehabilitation options for retinitis pigmentosa patients.
Tinting
Night vision goggles
Wide angle mobility lamp
Field expanders
Hand-held/computer assisted magnifiers
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.
None of these have been proven
What is the effect of vitamin A supplementation on retinitis pigmentosa ERG? What about VA and visual fields?
Slows decline in ERG amplitude
VA and visual fields not significantly affected
List two risks of taking high dose vitamin A.
Hip fractures
Birth defects (not recommended for pregnant women)
What is the effect of vitamin A supplementation on retinitis pigmentosa patients?
No clear benefit
Does light exposure in retinitis pigmentosa speed up degeneration? Explain.
In animals yes
In humans, there was no effect
List 4 possible future treatment options for retinitis pigmentosa.
Gene therapy
Nutritional/neuroprotective intervention
Transplantation (stem cells)
Implants
