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Genetics Fellowship > Retinal diseases > Flashcards

Flashcards in Retinal diseases Deck (118):
1

AMD risk factors

age, smoking, +FHx, female, light iris, hyperopia, HTN, hyperchol

2

what is the difference of soft vs hard drusen?

Hard: nodular thickening of BM of RPE• Soft: focal PED (separation from Bruch’s)

3

drusen size?

Small 64 mic; med 64-124, large>124

4

DDX Geographic Atrophy

1) central areolar choroidal dystrophy2) Sorsby macular dystrophy3) NC macular dystrophy

5

what is Cuticular (Basal Laminar) Drusen?

Type of early hard drusen (age 30-40s)• Many small, uniform, demarcated drusen,better seen on FA with“stars-in-the-sky” appearance• May develop large vitelliform detachment

6

what is reticular drusen? (PSEUDODRUSEN)

• Interlacing network of 125-250um drusen• First appear in superotemporal macula• Better seen on red-free, NOT on FA /ICG• “Sawtooth” subretinal deposits on OCT

7

AREDS– Components?

Vitamins C & E, beta carotene, copper, zinc

8

AREDS study details

25% reduction in progression to advanced AMD– 19% reduction in VA loss over 5 yrs– Criteria?• Bilateral intermediate (many int or 1 large)• Unilateral advanced AMD (wet AMD or GA)– Avoid in smokers?• Beta carotene

9

AREDS 2 components

Antioxidants w/o beta carotene• Omega-3 fatty acid• Xanthophylls (zeaxanthine, lutein)

10

Framingham Eye Study:

6% in age >65• 20% in age>75

11

Choroidal Neovascularization (CNV)• Classificaton?

Type 1– Under RPEType 2– Between RPE + photoreceptorsType 3– Retinal angiomatous proliferations (RAP)

12

classic CNV - on FA definition

Early hyper + late leakage

13

occult CNV definition

Stippled/granular early hyper + late stain– 2 types: fibrovascular PED vs. lateleakage of undetermined source

14

CNV types?

Predominantly Classic (>49% classic)– Minimally Classic (

15

Retinal Angiomatous Proliferation (RAP) classification

Stage 1– Intraretinal NV / leakageStage 2– Subretinal NV + serous PEDStage 3– Choroidal NV + fibrovascular PED– FA: retinochoroidal anastamoses

16

what is Pegaptanib (Macugen)

pegylated anti-VEGF RNA aptamer• binds VEGF 165• 0.3mg

17

what is Ranibizumab (Lucentis)

its:48kD Fab of Mab (

18

Bevacizumab (Avastin)

full-length Mab + Fc• targets VEGF-A• 1.25mg, 2.5mg

19

Aflibercept (Eylea)

ligand-binding domain of VEGFR ½ + IgG Fc• binds VEGF-A & placental-like GF• 2mg, 4mg

20

PDT- Regular vs. Reduced fluence?

Regular: 600mW/cm2- Reduced: 300mW/cm2

21

Vision Study

Macugen q6wks x 48wks > sham– improved VA in all CNV

22

MARINA

Lucentis q4wks x 2yrs > sham– Minimally-classic or occult w/o classic CNV

23

ANCHOR

Lucentis q4wks x 2yrs > PDT q3mo PRN– Predominantly-classic CNV

24

PIER

Lucentis q4wks x 3 then q12wks– Steady decline after 3mo c/w q4wks

25

PrONTO

Lucentis q4wks x 3 then PRN (VA loss + fluid, CRTinc, mac hem, new cl CNV, persistent fluid s/p inj)– Comparable to q4wks; 5.6inj/yr, but q4wk visits

26

SUSTAIN

Lucentis q4wks x 3 then PRN (VA loss, CRT inc)– Comparable to q4wks; 5.3inj/yr, but q4wk visits

27

HORIZON

MARINA/ANCHOR/FOCUS pts tx w/ PRN Lucentisq4wks s/p 2yrs– Continued less frequent dosing -> VA loss

28

CATT

Lucentis = Avastin q4wks or PRN in VA ( Avastin q4wks or PRN in OCT fluid (~10%)– Avastin > Lucentis in adverse events (24 vs 19%)

29

FOCUS

Lucentis + PDT > PDT alone– Predominantly-classic CNV

30

SUMMIT (MONT BLANC, DENALI, EVEREST)

Lucentis + PDT = Lucentis alone– Except IPCV (Lucentis + PDT > Lucentis)

31

CABERNET

Lucentis + epimacular brachy vs Lucentis

32

RADICAL

– Lucentis + PDT + Dexamethasone vs Lucentis

33

VIEW1 & 2

Eylea q1mo x 3 -> q2mo = Lucentis q1mo

34

HARBOR

Lucentis 0.5mg q4wks vs PRN vs 2mg q4wks vsPRN

35

AMD clinical trials

Marina - lucentisAnchor - lucentisCATT - avastinVIEW- Eylea

36

DME clinical trials

RISE & RIDE - lucentisDRCR.net - avastinVIVID/VISTA-DaVINCI- EyleaDRCR.net - triamcinoloneRetisert - ElliotFAME- Illuvien

37

RVO clinical trials

BRAVO/CRUISE - lucentisCRAVE - AvastinCOpernicus/Galileo/Vibrant - EyleaSCORE - triamcinoloneJaffe/Jain - Retisert

38

Causes of CNV?

1) AMD2) Myopic degeneration3) POHS4) Angioid streaks5) IPCV

39

what is Idiopathic Polypoidal ChoroidalVasculopathy (IPCV or PCV)

Multifocal, recurrent serous PEDs– Saccular choroidal outpouchings– More common in?• African-Caribbeans & Asians(accounts for >30% of exudativemaculopathy in Asian populations)

40

FA in Idiopathic Polypoidal ChoroidalVasculopathy (IPCV or PCV)

Early hyperfluorescent polyps andhypofluorescent halos• Polyps better seen on ICG

41

PCV treatment

Anti-VEGF, PDT, or combined• Only disease in SUMMIT trial tohave improved response tocombined anti-VEGF + PDT

42

what is Sorsby macular dystrophy

looks like GA- autosomal dominant- inherited dystrophy- by TIMP3 gene- normal vision until age of 40's- then develop BILATERAL multiple CNVs- later looks like GA with lots of pigment clumps, this is perhaps the differentiation- early they have mid-peripheral drusen, night vision problems

43

Malattia levintinese

-drusen distributed radially on the macula.- very similar to AMD-EFEMP1 gene, malattia levintinese is now thought to be a variant of Doyne's disease.

44

Doyne's honeycomb retinal dystrophy

-similar to those of AMD:-Symptoms typically arise during the fourth or fifth decade of life.- autosomal dominant pattern of inheritance.gene EGF-containing fibrillin-like extracellular matrix protein, abbreviated as EFEMP1. The protein, whose function is

45

CACD Central areolar macular dystrophy

-hereditaryatrophy of RPE and choriocapillaris-AD-gene: PRPH2 (previously known as RDS/peripherin

46

NC macular dystrophy

The disorder was initially described in a family of Irish descent in North Carolina, and affected individuals have been identified in European, Asian and South American families as well.

47

RAP lesions

its an occult CNV with proliferation of intraretinal capillaries in the paramacular area with contiguous telangiectasic response.Stage 1: intraretinial capillaries proliferationstage 2 subretinalstage 3 PEDstage 4 cnv- clinically similar to patients with AMD. -, these patients tend to be slightly older (80) than the patients with both classic and occult CNV. -bilateral, -lesions presenting juxtafoveally.-clinical features of RAP include retinal and preretinal hemorrhages as well as pigment epithelial detachments.

48

PCV

-its a form of intra-choroidal cnv-very common in Asian (>50% of AMD is PCV there) -characterized by large-caliber feeder vessels perfusing intrachoroidal branching arteriolar networks that terminate in one or more intrachoroidal polypoidal structures,-Cl

49

what is trichromatism?

that is normal color vision(mixture of red, green and blue)

50

what is protanopia?

Abnormal RED sensitive cone. confuse red and green

51

what is deuteranopia?

abnormal GREEN-sensitive cone. confuse reds and greens.

52

what is tritanopia?

abnormal BLUE-sensitive cone. confuse blue and yellow

53

the majority of color blind (or color weak we should say) are?

protanopes and deuteranopesNo problem with traffic lights because they can distinguish red from greenThey will have problmes for example distinguishing pink form green though.

54

what is the meaning of Tritan , protan and deutan?

tritan (blue-yellow)protan-deutan (red-green)

55

most color blindness is inherited in which way?

X-linked recessivethe most common color blindness is protanopia and deuteranopia and this are x-linkedthey are more common in man The tritanopia is AD but is very rare

56

what is achromatopsia?

absence of color discrimination.but its not only that unfortunately.they have nystagmus, photophobi and very poor vision.get an ERG

57

what percentage of general population are color weak?

5-8%

58

ERG in achromatopsia?

normal rod function but absent cone responses

59

CSNB inheritance?

X-linked (most common) -Xp11 rhodopsin geneADAR

60

tell me about CSNB

patients have night blindnessdifficulty seeing in the darkalso have myopia-nystagmus-poor vision-strabismusITS a RARE diseasemost common is x-linkedIts NON-progressive (or STATIONARY)symptoms present from birthTWO forms:complete - all pts have night blindnessincomplete - not all pts have night bllindness

61

mutations for CSNB?

NYX - completeCACNA1F - incomplete

62

x-linked inheritance? tell me more

x-linked (signigica que Affecta mas a los machos) machos X ....s-linked macho afectado.Macho Bueno no le pasa a su hijo.LAs mujeres son portadoras

63

CSNB exam?

vision 20/60 to 20/200normal DFEsevere myopianystagmussome patients do not complain of nictalopia (porque ya estan acostumbrados desde ninos)

64

what is a difference between CSNB and RP?

in RP there is photoreceptor damabe while in CSNB it appears to be a problem in the communication of photoreceptors with bipolar cells.That is why you see the NEGATIVE-ERG which is a normal a-wave but no b-wave

65

what is this ERG pattern?

its the negative ERGnormal a-waveabsent b-wave classic of CSNB

66

what is this fundus?what is the differential?how do you differenciate?

* fundus albino-puntata (FAP) (abnormal ERG that recovers with dark adaptation. Problem is that after light the rodopsin takes a long time to recover. * very similar to RETINITIS punctata albescence * the difference is that RPA es la prima de RP. So RPA has narrow vessels and severely depressed ERG.

67

RP has a cousin which one?

RPA retinitis punctata albesenceremember because of the word retinitismultple white dots in the retina. ERG severely depressed. narrow vessels.

68

what is this disease?patient has nictalopiathe DFE is abnormal, RPE  degeneraiton arounf vascular arcadesCME

enhanced-S-cone syndrome(S for short wavelength 0 blue catching cones affected)

69

how many geetic disroders affect the eye?

750!!!!they are listed in theOnline Mendelian Inheritance in Man (OMIM) RetNet lists 200 retinal degenerations

70

what % of pedigrees give useful info on the disease?

about 60%

71

most inherited eye disease are? uni or bil?

BILATERAL!!!!!!

72

ERG:non-recordable?

* LCA * RP * total retinal detachment

73

non-recordable PHOTOPIC ERG diagnosis of?

AchromatopsiaCone degenerationsx-linked blue monochromatism

74

What do you think with this ERG:non-recordable ROD-ERGabnormal bright adapted bright flashnormal Photopic ERG

CSNB

75

non-recrodable sctotopicabnormal photopic b-wave

RPLCAchoroideremiaretinitis punctata albesens

76

abnormal cone and ROD b-wave amplitudes

Cone-rod degenerations

77

negative ERG(in the dark-adapted ERG bright flahs light, the a-wave is noral but the b-wave is absent)

CSNBenhanced-S-cone dystrophyX-linked retinoschisisautoinmmune retinopathies

78

GVF i RP, which is early and which late on the disease?

left - earlyright - late

79

define RP

IS A GROUP of inherties retinal disorders characterized by photorecetor loss, abnormal VFs

80

RP without bone spicules is called?

retinitis sin pigmento

81

what is RP?

* is a group of reitnla disorders * characterized by progressive VF loss * and abnormal ERG  can be primary (affecting only eyes)secondary (affecting other organs)

82

* in RP, besides the * waxy ON pallor, * vessel narrowing bone spicules..... * what else can you find?

CMEno bone spicules (RP sin pigmento)loss of foveal reflexsmall PSC (usualy NVS) 

83

RP relatives?primos de RP? and their features?

* RPA retinitis punctta albsecense (deep white dots) * choroideremia (choriocapillaris atrophy) * RDS/perypherin mutations (RPE atrophy) * RP12 preserved parareteriolar RPE *    

84

RP ERG changes??

a-wave and b-wave abnormalb-w prolonged in time and diminished in amplitude 

85

what RP variant is this?

RPA

86

what to think in a pt with DFE looking like RP, blind but no fmaily hx of RP?

think also of mimmickers such as: * diffuse uveitis * crao old * paraneoplasic syndromes * retinal drug toxicity  

87

other rare variants of RP?

sectorial RPcentral RP (from center to periphery)pericentral RP (ring scotoma)

88

what type of RP is this?

sectorial RP 

89

how many differet GENETIC types of RP are there?

* more than 100\with more than 50 genes * the most common is ADRP (autosomal dominant RP - 20%) * the first tmutaiton discovered was in rhodopsin gene * RDS/perypherin mutaitons have a wide range form RP to pattern dystrophies

90

what is peripherin?

is a protein in the peripheral aspect of the photoreceptor discs

91

what is rhodopsin?

* it is a BIOLOGICAL pigment * it is a LIGHT SENSITIVE PIGMENT * found in ROD cells * it is a G-coupled proteinreceptor * very very sensitive to light * useful to allow vision in the dark

92

inheritance of RP

most common ADRP (20%)second Recessive RP (20%)XLRP (10%)40% have no family history in the US

93

tell me about LCA

it is the infantile and early childhood form of RP. * 9 mutations * most cases are AR * poor vision from birth * wondering nystagmus * abnormal ERG * oculodigital reflex * some vision from 20/200 to LP * fundus can be normal initially * later there can be ROUND pigment spots * normal inteligence * ERG is minimal or undetectable

94

what is CME in RP does not respond to acetazolamide?

try triamcinolone (mixed results

95

what can you tell me about RP treatments with Vit A?what about fish oil?light protection?

* some clinical trials shows some slower progression in patients receiving 15KU/day of vit A. But the risk of liver toxicity and teratogenicity in pregnant woman outweights the potential benefits. * fish oil appeared to not be efefctive (although pts with high DHA concentrations had slower progression. * an study with an opaque contact lens on one eye showed those patients did not have any different outcome in that eye compared to their control eye. Regardless, it makes sense to offer UV light protection

96

is cone dystrophy the same as color blindness?

NO!!!color blindness you are weak to see some colors but there is no retinal degeneration.Patients with color blindness are weak color perceivers but VQ is normal.colo 

97

tell me about cone dystrophies

progressive loss of VISION and COLOR DISCRIMINATION and HEMERALOPIA (day blindness) and  photophobia DFE is normal or bull's eye * group of diseases * onset in teenagers or youung adults * abnormal PHOTOPIC ERG * nromal rod-isolated SCOTOPIC ERG * nromal visual fields * soem could have normal full field ERG but abnormal pattern ERG at center * could be AD, AR, XL * 12 genes

98

if nictalopia is for RP, hemeralopia is for?

cone dystrophies

99

this fundus in a patient withpoor visionnormal GVFnormal scotopic ERGabnormal photopic ERGhemeralopia

cone dystrophies

100

tell me about cone-rod dystrophies

* on ERG the hotoptic and scotopic responses are abnormal * BUT.... * the photopic is way much worse than scotopic * (This can happen in stargardts as well) * this is a variant of stargardts?

101

tell me about Stargardts

* its the most common juvenile macular dystrophy * usually AR but few AD have been reported * ABCA4 gene which encodes for an ATP-binding cassette transported protein by rod outer segments * mutations in RDS/perypherin gene as well although less common * juvenile onset foveal atrophy * yellowish discrete flecks at levele of RPE * if flecks are dispersed then its called fundus flavimaculatus * dark choroid on FA (80% of stargardts patients) * dark choroid is very specific but the absence does not r/o the disease. * TRIAD: vision loss with 1) dark choroid 2) flecks 3) macular atrophy * slowly progressive

102

tell me about best disease

* AD maculopathy * due to mutation in VMD2 gene * chromosome 11 * gene encodes for bestrophin * bestrophine is in the lateral wall of RPE cell * bestrophin is a chloride channel protein. The malcfunction results in lipofuscin accumulaiton. * yellow yolk like lesion * breaks in to scrambled egg * late in disease looks like any macular dystrophy * 30% have extrafoveal lesions * GOOD vision. Many with 20/30!!! * CNV can develop and ruin the party in one eye * ERG normal * EOG abnormal * Arden ration is <1.5 and often <1.1 * Arden ration is the ratio of peak response to light compared to darkness

103

tell me about AOFMD

* adult onset * its a PATTERN dystrophy (meaning that is caused by RDS/perypherin gene * several bilagteral 1/3 DD in size with central dark pigment * patiwnets retain decent vision in one eye * AD * EOG is normal

104

tell me about FAMILIAL drusen

* this is drusen in YOUNGaptients (like 20 yo for ex) * numerous and different sizes * typically extramacular beyond arcades * most are AD but many no inheritance * if tiny drusen its cuticular drusen

105

tell me about pattern dystrophies

* are 4 Pattern dystrophies * AOFMD * Butterfly * reticular * fundus pulverulentus ALL have in common: * onset midlife * orange,gray, yellow deposits at RPE * AD * mpst AD forms are related to RDS/peripherin gene * phenotype can very among families and amoing eyes of the same patient! * most common presentaiton is decreased vision and metamorphopsia * ERG is normal * most patients retaiin reading vision in one eye * central atrophy is the final problem

106

tell me about Sorsby macular dystrophy

* BILATERAL subfoveal CNV * onset 40 y.o * AD * develop in to geagraphic atrophy * early sign is many drusen and RPE deposits bilateral in yound patient * gene is TIMP3 (metalloproteinase) * chromosome 22

107

50 y/o pt what is this?

AOFMD

108

young patient with this?

best disease

109

what pattern dystrophy is this?

butterfly

110

what is this drusen type?

familial drusen

111

what is this in a young patient?

startgardts

112

what is this? bilateral in a 40 y/o

Sorsbybilateral subfoveal CNV in a 40 y/o

113

genes for: * stargardts * AOFMD * sorsby * pattern dystrophies * best disease

* ABCA4 * RDS/perypherin * TIMP3 * RDS/peripherin * VMD2

114

good or bad prognosis for: * stargardts * best * AOFMD * familial drusen * pattern dystrophies * sorsby

* poor but slowly progressive * BEST and GREAT prognosis 20/30 * decent vision in one eye * good if not affecting fovea * retain reading vision in one eye * poor

115

inheritance for: * stargardts * best * AOFMD * familial drusen * pattern dystrophies * sorsby

AR (stargardts) * AD * AD * AD * AD * AD

116

BILATERAL subfoveal CNV in a young patient?

sorsby

117

how can you call the extramacular drusen?

familial drusen. IF:young patient 

118

where is the bestrophin and what is the action of it?

located at the lateral wll of RPE cellsits a chloride channel protein