Age-related macular

degeneration (AMD)
•ASSOCIATE PROFESSOR
TEA ČALJKUŠIĆ-MANCE,
MD, PHD
•DEPARTMENT OF
OPHTALMOLOGY
•MEDICAL FACULTY
•UNIVERSITY OF RIJEKA
Age-related macular degeneration      (AMD)

 Causes progressive damage to the macula

 The macula represents the central part of the retina of the eye and is responsible for clear central
vision 

The first sign is a feeling of blurring or dimming of vision

One of the leading reasons for vision loss in people of older age in developed countries

Central vision impairment reduces the possibility of functioning independently (reading, writing,
working on a PC, facial recognition, driving a car) (PUBLIC HEALTH PROBLEM)
                          Eye anatomy
What is AMD?
                                  AMD

 is an acquired degeneration of the retina that causes significant central visual impairment
through a combination of non-neovascular (drusen and retinal pigment epithelium
abnormalities), and neovascular derangement (choroidal neovascular membrane formation). 
Advanced disease may involve focal areas of retinal pigment epithelium (RPE) loss,
subretinal or sub-RPE hemorrhage or serous fluid, as well as subretinal fibrosis.
A genetic underpinning is inferred from its predilection to those of European ancestry,
although environmental, nutritional, and developmental (ie., aging) processes interact to
affect the degeneration observed in the macula.
Newly implicated biochemical pathways combined with a paucity of treatment options for
the majority of AMD  has created fertile ground for novel therapeutics.
     ETIOPATHOGENESIS AMD

Epidemiological demographic studies:

• BEAVER DAM EYE STUDY (USA)-completed 2010.
• BLUE MOUNTAINS EYE STUDY (AUSTRALIA)-
    completed in 2010., 20 years of monitoring
• ROTTERDAM EYE STUDY (NETHERLANDS)-2015.
• The severity of the disease increases with age
• Compared to people aged 55-69, people aged 70 and over are 6 times more likely
to have a later severe stage, and in people aged 80 and over 25 times more common
• AMD is closely related to age, but it's not just about ageing changes
                            Prevalence

• The prevalence of advanced AMD in the Beaver Dam Eye Study was
1.6%, with the exudative form being present in one eye 1.2% of the
time, and geographic atrophy in one eye 0.6% of the time
•  This population represented 4,926 people between the ages of 43 to
86 years of age. Similar prevalence data was noted in the
Framingham Eye Study, which reported a prevalence of exudative
AMD in those older than 52 years of age of 1.5%.
• The prevalence of AMD sharply increases in those 75 years or older
  COMPLEX GENETIC DISORDER due to
multiple gene variants that increase the risk
of the onset of the disease

In earlier studies, several genes  related to AMD:

ABCA4, ELOVL4, FIBL-6, APOE, 
     GENETIC        SOD2
BACKGROUND 
AMD Research from 2005 to the present day
identified 30 gene loci 
       associated with
ACTIVATION COMPLEMENTARY SYSTEM, 
      LIPIDS METABOLISM, OXIDATIVE
STRESS AND ANGIOGENESIS
Maximum single influence-genes for COMPLEMENTARY FACTOR H (CFH); The
Y402H gene that encodes the CFH component was the first to be identified, but the
genes encoding the other components of the complement also have an impact- factor
B (BF), C2, C3 and CFI.

In "genome-wide" studies, the association between hepatic lipase C (LIPC) and tissue
inhibitor metalloproteinase (TIMP3) with the formation of AMD was found.

LIPC is involved in the metabolism of HDL cholesterol, and TIMP3 is a factor in the
development of an early form of macular degeneration-Sorsby fundus dystrophy
Complementary factor H- in 4 independent research the association of CFH genes on chromosome
1q31 with the formation of AMD was established. Nucleotide polymorphism Y402H increases the
risk for AMD 18 TIMES.

Component of complementarity 3- polymorphisms of genes for C3 increase the risk to the

development of AMD. ARMS2's  gene on 10th chromosome raises AMD risk by 7.6 times

The combined influence of CFH Y402H, C3 and ARMS2 brings a risk of 76%, and by including
the CFB/C2 gene 86%.

SMOKING increases the risk by 2.4 times, and smoking in people with CFH Y402H increases the
risk by 34 TIMES
             PATHOPHYSIOLOGY AMD


The pathophysiology of AMD is complex and in combination with genetic
predisposition of at least 4 processes affect the development of the disease:

 LIPOFUSCINOGENESIS associated with  OXIDATIVE STRESS AND

system activation of COMPLEMENT.
 DRUZOGENESIS
 LOCAL INFLAMMATION
 NEOVASCULARIZATION
ACTIVATION OF
COMPLEMENT
    PATOPHYSIOLOGY 0F AMD
PROGRESSION OF
MACULOPATHY
                             AMD types
      DRY AMD

 atrophic, non-excedative-
common form,
 about 85% of cases are  this
type, expressed by
different degrees of atrophy in
the macular area
    progresses slowly, but with
great variability; at some
patients severe vision disorders
within 5-10 years
        WET AMD

 exudative, neovascular-aggressive
type,
 although the incidence is 15% it is
responsible for 90% of the
significant vision loss in AMD; is
more progressive, so it tends to
   severe changes occur within 3      years

It cannot be predicted with certainty
whether and when
  DRY form to move into WET
RETINAL PIGMENT
EPITHELIUM
(RPE)
DRY  AMD

Oxygen and nutrient deficit damages photoreceptors

Aging RPE cells lose ability of  phagocytosis of       

 these  molecules

An excess of metabolism of photoreceptors-debris and

hyalin material,DRUSEN

Degeneration occurs membranes and cells of

RPE,consequent ATROPHY and DAMAGE TO THE
CENTRAL VISION
WET AMD
Photoreceptors and RPE send a signal up to coriocapilaris for
pro-conducting new blood vessels

Neovascuralisation grow up from the coriocapilaris behind

the macula

Bruch's membrane collapse occurs newly created blood vessels

They're fragile and they shoot blood and fluid go out into space

A SCAR is created in the macula and causes SERIOUS VISION

DAMAGE 
           AREDS CLASSIFICATIONS
                    AMD
diagnostics
• Indirect ophtalmoscopy
• Indirect biomicroscopy
                      AMSLER TEST
AMSLER TESTING
FLUORESCEIN ANGIOGRAPHY
(FAG)
• Fluorescein angiography (FAG) is a
medical procedure in which fluorescent
dye is injected into the bloodstream to
highlight blood vessels in the back of the
eye so they can be viewed and imaged.
The FA test is helpful for making a
diagnosis, determining a treatment plan, or
for monitoring affected blood vessels.
OPTICAL COHERENCE TOMOGRAPHY
(OCT)
      OCT  IMAGES
OCT ANGIOGRAPHY, novel method
     AMD TREATMENT-DRY AMD
AREDS 2 STUDY
TREATMENT AMD-WET
  OLD TREATMENT
ANTI-VEGF INTRAVITREAL INJECTIONS
          NOVEL POSSIBILITIES
AGENTS-DRUGS

• BEVACIZUMAB (Avastin)-off label

• RANIBIZUMAB (Lucentis)
• AFLIBERCEPT (Eylea)
• BROLUCIZUMAB (Beovu)
• FARICIMAB?
LOW VISION REHABILITATION