MOHAMMAD REZA AKHLAGHI MD - PowerPoint Presentation

Slide1

Slide2

MOHAMMAD REZA AKHLAGHI MD

Slide3

HEREDITARY MACULAR DYSTROPHIES

Slide4

HEREDITARY MACULAR DYSTROPHIES

The hereditary dystrophies of the posterior segment constitute a large and

potentially confusing

group of disorders.

Slide5

CLASSIFICATIONS

ANATOMICAL CLASSIFICATIONS

have

divided the disorders by apparent layer of

involvement, such

as retina, macula, retinal pigment epithelium (RPE), choroid, and

vitreous-retina.

many

dystrophies overlap and may

have multiple

layers of involvement

.

INHERITANCE PATTERN

OF THE DISEASE:

Approximately 60% of

thorough pedigrees

give useful information.

DISEASE PHENOTYPE

by

clinical examination

AND ELECTROPHYSIOLOGIC

and

psychophysical testing

.

Careful

analysis of the information gathered by these

3 approaches

allows most

patients to be assigned to a disease group, and many can be given a specific

clinical diagnosis

that can be

CONFIRMED BY MOLECULAR TESTING

.

Slide6

Macular Dystrophies ~ Six Categories

1

. Nerve Fiber Disease

2. Photoreceptor &

RPE Diseases

3. RPE Diseases

4. Bruch’s

Membrane Diseases

5. Possible

Inflammatory Diseases

6. Miscellaneous

Macular Diseases

Slide7

Macular Dystrophies ~ Nerve Fiber Diseases

X-linked Juvenile

Retinoschisis

Familial

ILM Dystrophy

Slide8

Macular Dystrophies Photoreceptor & RPE

Cone Dystrophies

Other Bull’s Eye Lesions:

a.

Olivopontinocerebellar

atrophy

b. Benign Concentric Annular

c.

Duchenne

Muscular Dystrophy

Stargardt’s

Disease

Slide9

Macular Dystrophies ~ RPE Diseases

Best

Vitelliform

Dystrophy

Adult

Vitelliform

Dystrophy

Fundus

Flavimaculatus

Patterned

Dystrophy

Reticular

RPE Dystrophy

Dominant

Cystoid

Macular Dystrophy

Dominant

Drusen

Dominant

Radial

Drusen

North

Carolina

Macular Dystrophy

Slide10

Macular Dystrophies Bruch’s Membrane

1.

Sorsby’s

Macular Dystrophy

2.

Angioid

Streaks

3

. Age-related

Macular Degeneration

4. High Myopia

Slide11

PRESENTATION

The most common presentation is a history of slowly progressive central vision loss occurring in the first 3 decades of

life

With rare

exceptions, have

bilateral symmetric

involvement

.

When

unilateral

ocular involvement is seen,

other causes

,

such as birth defect, intrauterine or antenatal infection, and inflammatory disease,

should be considered

Slide12

Cone Dystrophies

Slide13

Cone Dystrophies

Characterized by :

loss of cone cell

Normal Rods

Cone dystrophies can be either stationary or progressive.

These different syndromes encompass a

wide range of clinical and psychophysical findings

Slide14

Cone Dystrophies

HISTOPATHOLOGY

The

outer nuclear

segment

of cones

had

disappeared

completely

RPE

showed pronounced pigment

changes

Slide15

Cone Dystrophies

Main Symptoms

loss

of visual acuity

,

from

20/100 to

CF

age of onset ranging from the late teens to the sixties

photophobia

hemeralopia

(day blindness)

dyschromatopsia

,

Slide16

Ophthalmoscopy :

Normal

fundus

in early stags

definite macular changes usually occur well after visual

loss

Bull's-eye pattern of macular atrophy

(consists of a doughnut-like zone of atrophic pigment epithelium surrounding a central darker area)

demarcated circular macular lesions.

Mild to severe temporal optic atrophy

Slide17

Slide18

Slide19

Slide20

Slide21

FLUORESCEIN ANGIOGRAPHY

Fluorescein

angiography

is a useful adjunct

it

may detect early changes in the retina that are too subtle to be seen by ophthalmoscope. For example, FA may reveal

areas of hyperfluorescence

, indicating that the RPE has lost some of its integrity,

Slide22

Slide23

Slide24

Electeroretiongraphy

(ERG

) remains the best test for making the

Abnormal

cone

function

The

relative sparing of

rod

In

more severe or longer standing cases,

subnormal

scotopic records.

Slide25

.

Slide26

INHERIDENCE

Cone dystrophy

usually

occurs

sporadically

. Hereditary forms are usually

autosomal dominant

, and instances of

autosomal recessive

and

X-linked

inheritance also occur.

Slide27

The

cone dystrophies should not be confused with congenital color blindness,

in

which there

are color deficits for specific colors but no

associated visual loss and

retinal degeneration and do not show signs of progressive disease.

Slide28

DIFFERENTIAL DIAGNOSIS

Other macular dystrophies

( Central

areolar pigment epithelial (CAPE)

dystrophy,

Stargardt's

disease, pattern dystrophy, Best disease . . .)

as well as the

hereditary optic atrophies

must be

considered

Fluorescent

angiography, ERG, and color vision tests are important tools to help facilitate diagnosis in early stages

Slide29

MAMAGMENT

reducing photophobia:

Dark

sunglasses

miotics

low vision aids

magnifiers

,

closed-circuit

television

devices

software

for

computer screen

text

enlargement

Slide30

Cone-Rod Dystrophies

CRDs are inherited retinal dystrophies that belong to the pigmentary retinopathies

group

The

term

cone-rod

comes

from

electroretino

-graphic

testing, in which the

cone-isolated ERG

waveform is proportionately worse than the rod-isolated signal, and

both are

abnormal

Prevalence of CRDs is estimated at

1/40,000

(thus, CRDs are ten times less frequent than RP)

Slide31

Clinical description

CRDs

present first as a

macular disease

or as a

diffuse retinopathy

with predominance of the macular

involvement

Slide32

SIGNS AND SYMPTOMS

In the first

stage

decreased

visual acuity

,

usually discovered at school,

does

not significantly improve with

spectacles

intense photophobia

variable

degree of

dyschromatopsia

Visual

field

loss

central

scotomas

, while periphery is

spared

Slide33

In the second

stage

night

blindness becomes more apparent

loss of peripheral

visual field progresses.

visual

acuity continues to decrease to a level where reading is no longer possible.

At

this stage, patients are

legally blind

(visual acuity

<20/400

Slide34

SIGNS AND SYMPTOMS

Fundus in

early stage

Normal

looking

macula

fine

macular

lesions

optic disc pallor,

particularly on the temporal

side

At

this stage, the question is to differentiate Stargardt disease, cone dystrophies

Slide35

Slide36

SIGNS AND SYMPTOMS

Slide37

SIGNS AND SYMPTOMS

Latter

stage

Pigmentary deposits resembling bone spicules, frequently in macular area

Attenuation

of the retinal vessels

Waxy

pallor of the optic disc

Various

degrees of retinal atrophy

Slide38

SIGNS AND SYMPTOMS

Slide39

SIGNS AND SYMPTOMS

Slide40

Slide41

SIGNS AND SYMPTOMS

fluorescein angiography

fluorescein

angiography and fundus

autofluorescence

show that the peripheral retina is also involved with heterogeneity in the fluorescence, but to a lesser extent than the

macula

.

Slide42

SIGNS AND SYMPTOMS

Slide43

SIGNS AND SYMPTOMS

Visual field

• Central

scotoma

appears first, preventing fluent reading

• Patchy losses of peripheral vision follow

• Severe loss of vision occurs earlier than in retinitis pigmentosa

Slide44

Slide45

SIGNS AND SYMPTOMS

Electroretinogram

(ERG)

•

Dramatic decrease of amplitudes of both a- and b-waves

• Predominant involvement of

photopic

(cones) over scotopic (rods) responses

Slide46

Electroretinograms

showing the responses to white stimuli of a normal

proband

and patients 1 to 3. DA indicates responses at dark adaptation at low (first row) and maximum (second row) stimulus intensity. The next row shows the dark-adapted oscillatory potentials. LA indicates single-flash responses at light adaptation. The cone flicker response was measured at 30 Hz

Slide47

INHERITENCE

Three

Mendelian

types of inheritance have been

reported

Today

, there are 13 genes responsible for

CRDs

(10 cloned, 3 mapped).

Slide48

DIAGNOSIS

Clinical diagnosis is based on the early decrease of visual acuity and photophobia, lesions in fundus,

hypovolted

ERG traces with predominant cone involvement, and progressive worsening of these

signs

Full

field ERG is the key test,

particularly when patients are

symptomatic

and show normal fundus at early

stages

It

is important to

repeating

the examination one or two years after it has been first established.

Slide49

DIFFERENTIAL DIAGNOSIS

Retinitis

pigmentosa

Leber’s congenital

amaurosis (LCA

)

Stargardt disease

Cone dystrophies

Slide50

MANAGMENT

light protection

Vitaminotherapy

filtrating spectacles to minimize photophobia

low vision aid

treating

the complications such as cataract, macular edema, inflammation,

Slide51

STARGARDT'S DISEASE &FUNDUS FLAVIMACULATUS

There is no consensus as to whether

Stargardt

disease and fundus flavimaculatus are two distinct diseases,

Because of

some

overlap

reports

of the presence of both entities within the same

pedigrees

evolution

of one entity into the other in the same individual over time

Slide52

Descriptionthe most common form of juvenile macular degenerationThe estimated prevalence is 1 in 8,000 to 10,000 individuals.This disease was first reported in 1909 by German ophthalmologist, Karl Stargardt The typical appearance in fundus flavimaculatus is these yellowish spots or flecks occupying the entire posterior pole out to the midperiphery, with or without a pigmentary maculopathyThe typical appearance of Stargardt disease, is a pigmentary maculopathy surrounded by yellowish white spots.

STARGARDT'S DISEASE &

FUNDUS FLAVIMACULATUS

Slide53

HistopathologyHistopathology of donated eyes has revealed that changes in the RPE and include increasingly excessive lipofuscin content and cell loss towards the macula.The changes in the retina parallel those in the RPE, including accumulation of lipofuscin in photoreceptor inner segments, loss of photoreceptors, and reactive Muller cell hypertrophy

STARGARDT'S DISEASE &

FUNDUS FLAVIMACULATUS

Slide54

GeneticAutosomal recessive mode of inheritance. In most cases, Stargardt macular degeneration is caused by mutations in the ABCA4 gene. Less often, mutations in the ELOVL4 gene cause this condition.

STARGARDT'S DISEASE &

FUNDUS FLAVIMACULATUS

Slide55

The ABCA4 protein transports potentially toxic substances out of photoreceptor cells. These substances form after phototransductionMutations in the ABCA4 gene prevent the ABCA4 protein from removing toxic byproducts from photoreceptor cells. These toxic substances build up and form lipofuscin in the photoreceptor cells and the surrounding cells of the retina, eventually causing cell death

STARGARDT'S DISEASE &

FUNDUS FLAVIMACULATUS

Slide56

MANIFESTATIONStargardt Macular Dystrophy begins to damage both eyes somewhere between the ages of 6 and 20, although visual impairment may not be apparent until as late as ages 30 to 40. Children first notice difficulty in reading, complaining of gray, black or hazy spots in the center of their vision. They report that a longer length of time is needed to adjust between light and dark environments.

STARGARDT'S DISEASE &

FUNDUS FLAVIMACULATUS

Slide57

Stargardt Macular DystrophyFundus Flavimaculatus

MANIFESTATIONS

Vision

loss is usually slow until the 20/40 level, then rapidly progressing to the 20/200 (legal blindness) level. Unfortunately, in some cases, vision can degenerate to 10/200 in a period of months.

Peripheral

vision and night vision are not lost for most people but color vision will be affected in the later stages.

Slide58

ophthalmoscopyfundus picture is characterized by the presence of multiple angulated or fishtail-shaped yellow-white lesions confined to the retinal pigment epithelium of the posterior pole The size, shape, and confluency of the yellow flecks vary considerably, and new clusters may appear periodically as old ones fade. The optic disc, retinal vessels, and periphery are normal in the early stage of the disease.

Stargardt Macular Dystrophy

Fundus Flavimaculatus

Slide59

Slide60

Rare cases of sub retinal neovascularization, retinal neovascularization, and cystoid macular change have also been reported in association with Stargardt

Stargardt Macular Dystrophy

Fundus Flavimaculatus

Slide61

Stargardt Macular DystrophyFundus Flavimaculatus

Fluorescein angiography

classically

reveals a dark

choroid.

The

reduced

visualization

of the choroidal circulation in

the early

phase of fundus fluorescein

angiography (FFA

) is secondary to excess lipofuscin accumulation in the RPE,

In early stage

hypofluorescent

on FFA

at

retinal

flecks

In

later stage they

appear

hyperfluorescent

due to RPE atrophy.

Slide62

Stargardt Macular DystrophyFundus Flavimaculatus

Slide63

Slide64

Electrophysiologic

Tests

The

ERG may be normal

or

show mild abnormalities

, but it is never

nonrecordable

The

EOG is usually subnormal,

suggesting a widespread defect in the retinal pigment epithelium. However, it is never as abnormal as is found in Best's

vitelliform

dystrophy

Visual-evoked responses are often subnormal, even with good vision and minimal fundus changes

and may be helpful in establishing an early diagnosis

.

Slide65

differential

diagnosis

an

atypical morphology suggests diseases such

as:

central

areolar choroidal

dystrophy

progressive

cone

dystrophy

vitelliform

macular

dystrophy

X-linked

retinoschisis

various

acquired macular

degenerations

The

yellowish white flecks may be confused

with

drusen

of Bruch's

membrane

fundus

albipunctatus

retinitis

punctata

albescens

multiple

vitelliform

cysts,

pattern

dystrophies of the

RPE

Slide66

Managment

Slide67