1-13,14 Inherited Retinal Dystrophies Flashcards
Causes/pattern of Retinitis Pigmentosa
50% unknown causes. Otherwise, when family history is given, either
- Autosomal dominant
- Autosomal recessive
- X-linked recessive
Describe fundus imaging features of retinitis pigmentosa
- Pathophysiology?
Peripheral bone spicule pigmentation
- Appears at mid stages of disease. Start at periphery, move towards macula.
- Pigmentation = RPE detached and once photoreceptors die, move to inner retina.
- Bone spicule = Pigment-containing cells migrate to perivascular (near BVs) sites of inner retina
- BV attenuation (sometimes sclerotic) because reduced metabolic demand or vasoconstriction due to hyperoxic areas where photoreceptors just died so aren’t using up any O2.
- Optic disc pallor at late stage caused by RNFL loss. Due to either ischaemia of surrounding BVs or astrocytic + CWS-like gliosis (Nerve-supporting glial cell fibrous proliferation). Pallor not due to ON degeneration but rather GC degeneration.
Fovea/macula unaffected.
Symptoms of retinitis pigmentosa
-> Night blindness (and dark adaptation) then
-> VF decrease then
-> tunnel vision then
-> legal blindness
- Can also complain of photopsia due to abnormal connections.
- Can eventually affect cones. Lesions seen as retinal pigment deposits in fundus. Affects CV.
Rare cases of retinitis pigmentosa can show…
Golden tapetal-like reflex.
- Unusual golden bright scintillating particulate reflection w/ relative sparing of fovea.
- Described in female carriers of X-linked RP.
List clinical hallmarks of retinitis pigmentosa
- Abnormal bone spicule deposits + attenuated BVs.
- Abnormal/diminished/missing a- and b-waves in electroretinogram
- Reduced VF
Describe ERG of retinitis pigmentosa
ERG consists of:
- A wave (photoreceptors)
- B wave (bipolar cells).
In RP,
- Scotopic light gives no response (rods)
- Photopic responses (and 30Hz which also stimulates cones) partially responds.
Risk factor for worsening retinitis pigmentosa?
- Light exposure
- Medications acting on phototransduction pathway
Describe congenitial stationary night blindness
- Pattern of inheritance?
- Do carriers experience symptoms?
- Two types?
- Symptoms?
- X-linked recessive defects of proteins that pass info from rods/cones to bipolar cells.
Carriers have no symptoms, although retinal changes can be detected w/ ERG. - Complete = rods only
- Incomplete = rods and cones.
In complete form,
- Affected night vision
- Reduced VA
- high myopia
- nystagmus
- strabismus
Stable throughout life.
Describe ERG of congenital stationary night blindness
- Rods no work (scotopic light = no response).
- Cones remain (so scotopic white actually gives some response with a-wave but b-wave not there because rods aren’t detecting and sending info to bipolars).
- Note: In incomplete CSNB, both a- and b-waves are affected based on severity since a- and b- correspond to cones and rod function.
Symptoms of cone dystrophies?
- Photophobia
- VA loss
- CV loss
- Nystagmus
- Eventually, total blindness as rods affected too.
Describe stargardt’s disease
- Pattern of inheritance
- Appearance?
- Autosomal recessive
- Atrophic pigmentary macular changes
- Choroidal silence (due to blood flow reduction)
Overall variable expression. Look for darker patch at/around macula and darker spot at fovea.
Symptoms of stargardt’s disease
- Wavy vision
- Blind spots
- Blurriness
- Impaired CV
- Dim light adaptation harder
Mechanism of stargardt’s disease
Normally, rhodopsin + light -> all-trans-retinal. This is then combined w/ phosphatidylethanolamine (PE) to be transported via ABCA4 to cytosolic face of disc where it reduces to all-trans-retinol before being sent to RPE for recycling.
In stargardt’s, ABCA4 responsible for retinal + PE complex transportation is mutated. This means retinal-PE complexes build up in disc. The discs get phagocytosed and the retinal-PE complexes “poison” the RPE so it accumulates lipofuscin permanently until eventually RPE death and photoreceptor degeneration.
Two genes associated w/ stargardt’s disease?
ATP-binding cassette sub-family B member 1 (ABCA) Peripherin-2 (PRPH2). Essential for coding the correct shape of outer segment disc. Mutation can also cause lipofuscin accumulation.
Describe fundus flavimaculatus
- Underlying mechanism?
- Symptoms?
- Fundus appearance?
- Similar to stargardt’s disease
- RPE atrophy increase
- CV loss, paracentral scotoma, and photophobia.
- Macula pigment change
- Retinal flecks (elongated yellow-white deposits) across macula and mid-perihery. Become fuzzy, undefined, and grey w/ time so requires autofluorescence to see properly and show the discrete areas they are in to rule out retinal degeneration.
What can make stargardts or fundus flavimaculatus worse?
Excessive Vit. A consumption due to more visual pigment that can’t be carried out of cell
Describe Leber’s Congenital Amaurosis
1) What cells it affects?
2) Clinical appearance?
3) Symptoms?
4) Which gene is affected?
1) Both rods and cones.
2) Retinitis pigmentosa signs but also affects macula and:
- No/little autofluorescence
- OCT shows retinal thinning.
3) Blindness at birth or childhood.
4) RPE65 (Convert all-trans retinal to 11-cis retinal)
1) Best’s Vitelliform dystrophy appearance? Pattern of inheritance?
2) Lesions are located where?
3) Stages?
1) egg-yolk form at fovea. Autosomal dominant.
2) Between RPE and bruch’s membrane. Most cases are central but can be peripheral too.
3)
- Pre-vitelliform
- Vitelliform
- Vitelliruptive (scrambled egg)
- Scar (vascularised or atrophic)
Visual loss depends on stage.
Best’s disease pathogenesis?
Bestrophin, is created by VMD2 (Best vitelliform macular dystrophy gene). In Best’s disease, bestrophin is abnormally located from apical to basal side of RPE cell causing abnormal differentiation. This affects stuff like which side has what transporters.
Abnormal lipofuscin deposition between RPE and bruch’s membrane leading to geograpghic RPE atophy and drusen.
Symptoms of albinism (ocular)?
Clinical appearance?
Which gene affected? Pattern of inheritance?
- Photophobia
- Low VA (Hypoplasia at fovea due to not enough melanin from RPE. Macula doesn’t degenerate though, just malfunction)
- Nystagmus
- No binoc vision (abnormal chiasm crossing)
Pink eye, hypopigmented fundus, visible choroid vessels.
Tyrosinase gene = Autosomal recessive
