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.
