W11 Retinitis Pigmentosa Flashcards
RP description:
Group of disorders.
Inherited progressive rod/cone degeneration
Syndromic (35%) or non-syndromic (systemic assoc.)
Causes progressive central/peripheral vision loss
RP common gene:
AD: RHO at 3p22.1
10% mutation of (RhoPro23His) > “typical RP”
Mutation of cys-187-tyr > rapid degeneration
Mutation of thr-58-Met > slow mild sectoral
RP genetic description:
AR: 55% non-syndromic retain central vision till 60
AD: 40% best prognosis
X-linked recessive: rare, most severe. Blind by 40
Patho of RP mutations:
Mutation alters proteins for PR structure/phototransduction/visual cycle > altered rhodopsin/RPE function > signalling cascade > PR apoptosis
RP remodelling patho:
PR loss > RPE dysfunction >
RPE hyperplasia / inward migration (bony spicules)
Glial cell migration/proliferation (ON pallor)
PR loss > O2 consumption loss > BV attenuation
RPE degen. > BRB loss > intraretinal fluid leakage > macula edema
RP symptoms:
Nyctalopia: initial Rod loss
Peripheral loss: Tunnel vision from Rod loss
Photophobia: Rod/Cone loss > doubled recovery time for photopic stress
Photopsia: altered PR signals > peripheral shimmering
RP signs:
Bony spicules: interstitial pigment clumps
ON pallor: white/waxy from Gliosis/ganglion death
BV attenuation: PR loss > attenuation / CC atrophy
Macula oedema: BRB loss > leakage
ERM: Atrophy/BRB loss > proliferative vitreoretinopathy
Bulls eye maculopathy / PSC / Vit. Degen.
Syndromic RP types:
Syndromes associated with RP forms
Bassen-kornweig syndrome
Refsum disease
Kearns-Sayre syndrome
Bardet-Beidel Syndrome
Usher syndrome
Kearns-Sayre syndrome:
Sporadic mitochondrial DNA mut. > energy loss
Chronic progressive external ophthalmoplegia (EOM weakness) / ptosis
RP (macula salt/pepper)
Cardaic loss, dementia
Bassen-Kornweig syndrome:
AR mutation > lipoprotein def. > vit. Absorbtion loss
RP by 10y, reduced w/ vitamin supp.
Spinocerebellar ataxia (motion loss)
Acanthocytosis (thorny red BCs)
Refsum disease:
AR PEX7 mutation > enzyme PA hydrolase def. > Systemic phytanic acid accumulation
Infant RP (salt/pepper) w/mental loss, scaly skin
Low phytanic acid diet decreases progression
Atypical RP types:
Diseases related-to/forms-of RP
Cone-rod dystrophy
RP sine pigmento
Retinitis puncata albescens
Sector RP
Pigmented paravenous chorioretinal atrophy
Bardet-beidel syndrome:
AR mut. In BBS gene > cell cilia dysf. > signalling pathway loss
Polydactyly (extra appendage), HT/DM, obesity
Bulls eye maculopathy
Ushers syndrome:
Type 1 (75%): Deaf by 1y, RP in child
T2 (23%): adolescent hearing loss
T3 (2%): progressive / late deafness/RP
Salt/pepper pigment / cataract
Cone-Rod dystrophy:
Early RP sign
Poor central vision > late peripheral loss > nyctalopia
RP sine pigmento:
Rod loss wo/pigment
Bony spicules late development
Retinitis punctata albescens:
AD/AR variant
Peripheral white scatted dots w/ arterial attenuation
Gradual peripheral loss/nyctalopia
Sector RP:
AD variant
Typical pigment in inferior quadrant
Progresses throughout retina
RP management:
Ophthal reff. > electrophysiological/genetic testing
Low Vision Service reff. > Royal society of the blind > visual aids (service dogs, counselling, employment)
Pigmented paravenous chorioretinal atrophy:
AD variant
Asymptomatic non-progressive
Bony spicules wo/vision loss
Most common macular dystrophy:
Stargardt disease and fundus flavimaculatus (variations of same condition)
AD mutation in ABCA4 gene > rod OS metabolism dys. > ^RPE lipofuscin
VA 6/60
Round/pisciform yellow flecks on fundus
BEST vitelliform macular dystrophy patho:
Second most common macular dystrophy
Bestrophin gene (BEST1) AD mutation on chromosome 11q13
Altered RPE BEST ion channel > ^metabolic by-product above RPE
^by-product size > CNV / geographic atrophy
Forms of macula dystrophy:
Stargardt disease / fundus flavimaculatus
BEST vitelliform macula dystrophy
Sorsby fundus dystrophy
X-link juvenile retinoschisis
AD drusen
BESTs disease stages:
Pre-vitelliform stage
Vitelliform stage
Pseudohypopyon stage
Vitelliruptive stage
Atrophic stage
Stargardt disease and FFM signs:
Present 10-20yo w/ central vision loss
Mottled/metal macula > bulls eye maculopathy/atrophy
Pisciform (fish shape) flecks on fundus
BEST disease first 3 stages:
Pre-vitreliform: abnormal EOG
Vitrelliform: vitrelliform lesion (yellow drusenoid PED) at macula 6/18
Pseudohypopyon: weight of material > inferior PED development
BEST 4/5th stage:
Vitrelliruptive: lesion disruption (scrambled egg) 6/60
Atrophic: chorioretinal atrophy at macula > retina thinning > scarring ^6/60
Sorsby fundus dystrophy patho:
Rare macula dystrophy
AD mutation in TIMP3 > altered inhibition of MMP-3 > by-product buildup in RPE
Characteristic yellow drusen-like deposits along arcades
Sorsby fundus dystrophy signs:
Presents from 30y
Nyctalopia, metamorphopsia, altered colour vision
Exudative macula degeneration from 50y
X-link juvenile retinoschesis signs:
Present by 10y w/secondary nystagmus/strabismis
Vision stabilises by 20, then degrades after 50
Peripheral retinoschisis in 50% Px
X-link juvenile retinoschisis patho:
RS1 gene mutation > altered retinoschisin protein secretion from PRs > poor cell-cell adhesion > NFL splitting
Characteristic spoke wheel splits in macula
Autosomal dominant drusen:
EFEMP1 gene mutation > RPE matrix protein loss > drusionoid deposits
AMD by 20
Increasing drusen at macula > confluence > geographic atrophy/CNV by 50
CSNB patho:
Congenital stationary night blindness is a group of inherited retinal dystrophies affecting PR/bipolar/phototransduction cascade
Loss of retinal signalling > vision loss / fundus changes / altered ERG
Lebers congenital amaurosis signs:
Blindness soon after birth > roving eye, nystagmus, photophobia
Low pupil light reflex
Arteriolar narrowing
Salt/pepper retinopathy > severe pigmentation
Systemic association w/deafness, epilepsy
Lebers congenital amurosis patho:
Severe AR rod-cone dystrophy in kids
Mutation in RPE65, CRB1, CEP290 > altered phototransduction cycle
Characteristic Franceshetti’s oculodigital sign of eye rubbing > keratoconus/deep set eyes
CNSB symptoms:
Nyctalopia w/poor light-dark adaptation
Photophobia, strabismus, nystagmus
Varied fundus: pigmented, scattered dots
ERG shows low red response, normal cone
Retinal dystrophy management:
Ophthal refferal > Electrooculography / Electroretinography / gene testing
Genetic counselling (family)
Low vision aids (dogs)
Gene therapy for RPE65 can improve prognosis
Electrophysiological testing:
Evaluate RPE / retina function
International Society for Clinical Electrophysiology of Vision developed guide for:
Full-field/Pattern/Multifocal electroretinogram (ERG/PERG/mfERG)
Electrooculogram (EOG)
Cortical-derived visual evoked potential (VEP)
Electroretinography:
Electrodes placed on cornea / lower lids
20m Dark adaptation > 0.01/3/10 cd.s.m^-2 flash
10m light adaptation w/ bg luminance 30 cdsm > 3.0 cdsm flash at 3/30 Hz
Assessment of electroretinography:
DA 0.01: Rod / rod-bipolar
DA 3/10: Rod / Cone (rod dominance)
LA 3 / 30Hz flicker: Cone / cone-bipolar
Electroretinogram waveform:
A-wave: PR function (rod/cone for DA/LA)
Oscillating potentials: amacrine cells
B-wave: bipolar (rod/cone for DA/LA)
C-wave: RPE (requires functioning PRs)
Pattern electroretinogram:
Asses macula via alternating high-contrast checkboard stimuli
Multifocal electroretinogram:
Display of small hexagons evaluate localised function and disease progression
Electrooculogram:
Measures RPE by 15m DA followed by 15m LA (100cdsm)
Ratio between dark trough and light peak is called Arden ratio
Represents function of RPE/PR complex
Visual evoked potential:
Electrodes on scalp note ON and visual cortex response to checkerboard patterns
Useful in non-verbal Px
