Age-related

Macular degeneration
OPHTHALMOLOGY ROTATION
Table of content
Anatomical Landmarks

•Epidemiology
Introduction • Risk factors

2
Drusen

Non-exudative (dry, non-neovascular)

AMD
• Serous PED
Retinal pigment epithelial • Fibrovascular PED
detachment • Drusenoid PED
• Haemorrhagic PED

Retinal pigment epithelial tear

Choroidal
neovascularization (CNV)

Haemorrhagic AMD
Anatomical Landmarks
Macula
• Round area at the posterior
pole, lying inside the temporal
vascular arcades
• Between 5 and 6 mm in
diameter
• More than one layer of
ganglion cells
• Inner layers: yellow
xanthophyll carotenoid
pigments lutein and
zeaxanthin
• “Macula Lutea” – yellow
plaque
Fovea
• depression in the
retinal surface at the
centre of the macula,
with a diameter of 1.5
mm – about the same
as the optic disc.
Foveal Avascular Zone
(FAZ)
• central area containing no blood
vessels but surrounded by a
continuous network of capillaries
• located within the fovea but
extends beyond the foveola
• varies with age and in disease, and
its limits can be determined with
accuracy only by fluorescein
angiography (average 0.6 mm)
Foveola
• forms the central floor of
the fovea
• 0.35 mm diameter
• thinnest part of the retina
• devoid of ganglion cells
• consisting only of a high
density of cone
photoreceptors and their
nuclei, together with Müller
cells
Umbo
• depression in the very centre of
the foveola
• corresponds to the foveolar
light reflex
• loss may be an early sign of
damage
Retinal Pigment Epithelium (RPE)
 Cont..
FUNCTION
 Outer blood–retinal barrier
• RPE cells and intervening tight junctional complexes (zonula
occludentes)
• Prevent extracellular fluid leaking into the subretinal space from the
choriocapillaries
 Its integrity, and that of the Bruch membrane continued
adhesion between the two
• due to a combination of osmotic and hydrostatic forces with the aid
of hemidesmosomal attachments
 Cont..
FUNCTION
Facilitation of photoreceptor turnover by the phagocytosis and
lysosomal degradation of outer segments following shedding.
Preservation of an optimal retinal milieu.
• a key factor
• as are the inward transport of metabolites and the outward transport
of metabolic waste products.
Storage, metabolism and transport of vitamin A in the visual cycle.
The dense RPE pigment absorb stray light.
Bruch membrane
• separates the RPE from the
choriocapillaries
 Cont..
FUNCTION
Utilized by the RPE as a route for the transport of metabolic waste
products out of the retinal environment.

Changes in its structure are thought to be important in the

pathogenesis of many macular disorders
 example: intact Bruch membrane may be important in the
suppression of choroidal neovascularization (CNV)
Symptoms
Blurred vision and difficulty with close work may be an
early symptom.

A positive scotoma, in which patients complain of something

obstructing central vision

Metamorphopsia (distortion of perceived images)

Micropsia (decrease in image size)

Macropsia (increase in image size)

Color discrimination may be disturbed

Difficulties related to dark adaptation, such as poor vision

in dim light and persistence of after-images, may occur
Age-related Macular Degeneration
a degenerative disorder affecting the macula.
characterized by the presence of specific clinical findings, including drusen
and RPE changes, in the absence of another disorder.
 Conventional Classification
Dry (non-exudative, non-
neovascular) AMD
• most common form
• 90% of diagnosed disease
 Geographic atrophy (GA)
—advanced stage of dry AMD
Wet (exudative, neovascular)
AMD
• much less common than dry
• associated with more rapid
progression to advanced sight loss
• main manifestations:
 CNV
 PED
 retinal angiomatous proliferation (RAP)
 polypoidal choroidal vasculopathy
(PCV)
 Epidemiology
most common cause of irreversible visual loss in industrialized countries.
In the USA
o 54% of severe sight loss (better eye worse than 6/60) in Caucasian
increases with age
 rare in patients under 50 years of age
Patients with late AMD in one eye, or moderate vision loss due to non-advanced
AMD in one eye
— 50% chance of developing advanced AMD in the fellow eye within 5 years.
 RISK FACTORS
Smoking
Age
Hypertension
& other cardiovascular
risk factors
RACE
ASPIRIN
Hereditary
Dietary factors
Clinical Evaluation
Visual acuity or Near visual
acuity

Contrast sensitivity

Amsler grid

Color vision
Investigations
Optical coherence tomography

Fundus fluorescein angiography

Indocyanine green angiography

Drusen
Histopathology

White or yellowish Extracellular deposits

located at the interface between the RPE and Bruch membrane

Thought to be derived from immune-mediated and metabolic

processes in the RPE

Associated with the size of lesions and the presence or absence

of associated pigmentary abnormalities

Common by the sixth decade.

The distribution is highly variable.

Clinical Features
There is a strong association between the size of drusen and the risk of
developing late AMD over a 5-year

SMALL DRUSEN (DRUPELETS) • ‘soft’ drusen

• As they enlarge and become more
INTERMEDIATE DRUSEN
numerous, they may coalesce giving a
localized elevation of the RPE, a
PIGMENTARY ABNORMALITIES
‘drusenoid RPE detachment’.

LARGE DRUSEN

DYSTROPHIC CALCIFICATION
Fluorescein angiography (FA)
 Hyperfluorescence can be caused by a window
defect due to atrophy of the overlying RPE, or by
late staining.

 Hypofluorescent drusen masking background

fluorescence are hydrophobic, with a high lipid
content, and tend not to stain.
Optical Coherence Tomography
(OCT)
 Medium-sized and large drusen are seen as

hyper-reflective irregular nodules

beneath the RPE, on or within the Bruch
membrane.
Non-exudative (Dry, Non-neovascular) AMD
Diagnosis

Symptoms consist of gradual impairment of

vision over months or years.

Both eyes are usually affected, but often

asymmetrically.

Vision may fluctuate, and is often better in bright

light.
Non-exudative (Dry, Non-neovascular) AMD
Signs in approximately chronological order:

Numerous intermediate–large soft drusen; may become confluent.

Focal hyper- and/or hypopigmentation of the RPE.

Sharply circumscribed areas of RPE atrophy associated with variable loss of

the retina and choriocapillaris.

Enlargement of atrophic areas,Visual acuity may be severely impaired if the fovea is

involved.

Drusenoid RPE detachment.

Optical Coherence Tomography
(OCT)
• Drusen
• Loss of RPE and morphological alterations of
the overlying retina of increasing severity are
seen in GA
• Outer retinal tubulations
• Outer retinal corrugations
Fluorescein angiography (FA)
Atrophic areas show a window
defect due to unmasking of
background choroidal fluorescence,
if the underlying choriocapillaris is
still intact. Exposed sclera may
exhibit late staining.
 Management
o Prophylaxis

—Antioxidant supplementation if indicated.

—Risk factors should be addressed

(smoking, ocular sun protection, cardiovascular, dietary)

o Amsler grid (self test;regular basis)

 Management
• Provision of low vision aids
• Experimental surgery
• Potential new therapies
○ Lampalizumab,
○ Visual cycle modulation
○ Photocoagulation of drusen
○ Saffron (20 mg/day)
○ subretinal stem cell transplantation, and intravitreal injection
 
Retinal Pigment Epithelial Detachment
Pathogenesis

Pigment epithelial detachment (PED)

from the inner collagenous layer of
Bruch membrane

Caused by disruption of the physiological

forces maintaining adhesion

The basic mechanism is thought to be the

reduction of hydraulic conductivity of a
thickened and dysfunctional Bruch
membrane, thus impeding movement of fluid
from the RPE towards the choroid.
Types of Pigment Epithelial Detachment
SEROUS PED FIBROVASCULAR PED DRUSENOID PED HAEMORRHAGIC PED

An orange dome- much more Shallow elevated Elevated dark red

shaped elevation irregular in outline pale areas with dome-shaped lesion
with sharply and elevation than irregular scalloped with a well-defined
delineated edges serous PED edges outline.
FA shows hyperfluorescence

ICGA shows hypofluorescence with a faint ring

surrounding hyperfluorescence
Retinal Pigment Epithelial Tear

may occur at the junction of attached and

detached RPE.

Tears may occur spontaneously, following laser (including

PDT), or after intravitreal injection.

Higher Risk—— Older patients and large irregular PEDs

associated with CNV
 Retinal Pigment Epithelial Tear
CLINICAL MANIFESTATION

• Sudden fall in vision with foveal involvement

• crescent-shaped pale area of RPE dehiscence,
next to a darker area corresponding to the
retracted and folded flap
 Retinal Pigment Epithelial Tear
OCT
Loss of the normal dome shape of
the RPE layer in the PED, with hyper-
reflectivity of the folded RPE

FA
Late phase shows hypofluorescence over the
flap due to the thickened folded RPE, with
adjacent hyperfluorescence, initially over the
exposed choriocapillaris where the RPE is absent
and later due to scleral staining.
The two areas are often separated by a sharply
defined border
Choroidal Neovascularization (CNV)

consists of a blood vessel complex that extends

through Bruch membrane from the choriocapillaris into the
sub-RPE (type 1) or subretinal (type 2) space

It occurs in many different disorders, usually when Bruch

membrane and/or RPE function has been compromised by
a degenerative, inflammatory, traumatic or neoplastic
process.

AMD is the most common causative association, followed

by myopic degeneration.
CLINICAL MANIFESTATION

Acute or subacute painless blurring of vision, usually

with metamorphopsia.

Haemorrhage may give a positive scotoma.

SIGNS
grey–green or pinkish-yellow lesion

Associated medium–large drusen

Localized subretinal fluid

Intra- and subretinal lipid deposition

Haemorrhage is common, e.g. subretinal,

preretinal/retrohyaloid, vitreous
Associated serous, fibrovascular drusenoid or
haemorrhagic PED.
Retinal and subretinal cicatrization (‘disciform’
scar) in an evolved or treated lesion
Fluorescein Angiography

FA was previously used to diagnose CNV and to plan and

monitor the response to laser photocoagulation or PDT.

Current indications include:

• Diagnosis of CNV prior to committing to anti-VEGF
treatment;

• As an adjunct to diagnosis of an alternative form of

neovascular AMD such as PCV and RAP

• Localization for extrafoveal photocoagulation, or guidance

for PDT.

• Monitoring is now predominantly with OCT.

 Fluorescein Angiography
Classic CNV (20%)
• fills with dye in a well-defined ‘lacy’ pattern during
early transit, subsequently leaking into the subretinal
space over 1–2 minutes with late staining of fibrous
tissue .
Occult CNV (80%)
• used to describe CNV when its limits cannot be fully
defined on FA
Predominantly or minimally classic CNV
• classic element is greater or less than 50% of the
total lesion respectively
 Optical Coherence Tomography

Critical in quantitative monitoring of the

response to CNV treatment.

CNV is shown as a thickening and

fragmentation of the RPE and
choriocapillaris.

Subretinal and sub-RPE fluid, blood and

scarring

Outer retinal tubulations may be present

 Indocyanine Green Angiography
demonstrates CNV as a focal hyperfluorescent ‘hot spot’ or ‘plaque’

• Increased sensitivity in the detection of

CNV

• The distinction of CNV from other

conditions particularly PCV, RAP and CSR.

• The delineation of occult CNV and for

patients who refuse intravitreal therapy.
Treatment with Anti-VEGF Agents

Principles. Inhibitors of VEGF block its interaction with

receptors on the endothelial cell surface and so retard or
reverse vessel growth

Indications.
All CNV subtypes respond to anti-VEGF therapy, but
benefit is only likely in the presence of active disease; the
presence of a mature fibrotic disciform scar with little or no
fluid makes treatment extremely unlikely to be useful.

Technique of intravitreal injection

Treatment with photodynamic therapy (PDT)

Verteporfin

It is infused intravenously and then activated by diode laser to cause

thrombosis.

The main indication was previously subfoveal predominantly classic CNV

with visual acuity of 6/60 or better.

Laser

Thermal argon or diode laser ablation of CNV is now rarely used

Haemorrhagic AMD

visual prognosis for most eyes with extensive subretinal or

sub-RPE haemorrhage is relatively poor.
 Reference
Kanski’s Clinical Ophthalmology 8th
Edition
Thank you