Transcript Age related Macular Degeneration

AGE RELATED MACULAR
DEGENERATION
AMD epidemic of aging
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Prediction by United Nations 606 million over
age 60 in 2000 will go to 2 billion by 2050
Population aged over 80 is expected from 69
million in 2000 to 379 million by 2050
Emergence conditions that are related to
aging
AMD
(Age related Macular Degeneration)
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Leading cause of sever visual loss in western
world in people over 50 years of age
Senile macular degeneration given by Haab
as early as 1885
ARM: age related maculopathy
AMD
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Second only to cataract as the cause of sever
visual loss
U.N. estimates 20-25 million with AMD world
wide
Prevalence of AMD 1.2% to 29.3%
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1.7% in US
1.4% in Australia
4.7% in north India
Normal Macula
How does normal vision occur
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Macula is an area up to 5.5mm with the fovea
at its centre
Highest concentration of photoreceptors
High resolution visual acuity
Entire process requires O2 and nutrition from
choriocapillaries
MACULA: CROSS SECTION
AMD: Etiology
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Complex and poorly understood
Transport between choroid and
photoreceptors may be involved
Angiogenesis is likely to be an early feature
of neovascular AMD
Types of AMD
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Dry macular degeneration
Wet macular degeneration
Dry AMD
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About 90% of all cases
Also called atrophic, nonexudative or
drusenoid macular degeneratin
AGE RELATED MACULAR DEGENERATION
Insufficient oxygen and nutrients
damages photoreceptor molecules
With ageing, the ability of RPE cells to digest these molecules
decreases
Excessive accumulation of residual bodies (drusen)
RPE membrane and cells degenerate and atrophy sets in and central
vision is lost
AGE RELATED MACULAR DEGENERATION
Alternatively the photoreceptors and pigment epithelium send a distress
signal to choriocapillaries to make new vessels
New vessels grow behind the macula
Breakdown in the Bruch’s membrane
Blood vessels are fragile
Leak blood and fluid
Scarring of macula
Potential for rapid severe damage
DRY MACULAR DEGENERATION
Drusen
 Drusen is an aggregation of hyaline material located
between Bruch’s membrane and RPE
 Drusen are composed of waste products from
photoreceptors
 Drusen > 63 microns in diameter are statistically
associated with visual pathology and are termed
early ARMD
 Hypo/hyper pigmentation of RPE may be present
DRY MACULAR DEGENERATION: VISUAL
WET MACULAR DEGENERATION
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Accounts for about 10%
Also called choroidal neovascularization,
subretinal neovascularization or disciform
degeneration
Abnormal blood vessels grow beneath the
macula
These vessels leak blood and fluid into the
macula damaging photo receptors
Progresses rapidly and can cause severe
damage to central vision
WET MACULAR DEGENERATION: VISUAL
AMD: COURSE AND VISUAL PROGNOSIS
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Patients with only drusen (in one or both eyes)
typically do not have much loss of vision, but
they make require additional magnification of
the text and more intense lighting to read small
point
Presence of large drusen (> 63 microns in
diameter) is associated with a risk of the late
form of the disease
Patients with large drusen are at relatively high
risk for choroidal neovascularization (CNV)
AMD: SYMPTOMS
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Initial symptoms are:
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Blurry vision
Distorted vision
Straight lines appear wavy
Objects may appear as the wrong shape or size
A dark empty area in the centre of vision
AMD: SYMPTOMS VISUAL
AMD: SYMPTOMS
Patient’s ability to perform normal daily tasks
such as reading, sewing, telling the time,
driving are greatly impaired.
AMD: EFFECT ON QUALITY OF LIFE
AMD: ESTABLISHED AND POSSIBLE RISK FACTORS
Established Risk Factors
Possible Risk Factors
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Older age (> 60 years)
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Female sex
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Family history
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Light-colored iris
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Cigarette smoking
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Cardiovascular disease
Low dietary intake or plasma
concentrations of anti-oxidant
vitamins and zinc
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What are the Risk Factors for AMD?
There are currently 5 specific risk factors that are
strongly associated with the development of AMD:
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Caucasian Ancestry
Genetic Component
Hypertension
Aging
Smoking
(SO QUIT NOW!!!!)
AMD: DIAGNOSIS
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Visual acuity is tested using the standard eye chart. It measures
vision at various distances and can detect vision loss
Amsler grid test: Assesses distorted or reduced vision and small
irregularities in the central field of vision
Retinal examination: Done through slit lamp microscope
examination: to detect drusen, as well as neovascularization
Fluoroscein angiography: Determines the presence and location
of neovascularization
Amslir Grid
DRY AMD: MANAGEMENT
Low vision aids
 Antioxidants
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Preventative Approaches for
AMD
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The AREDS formulation should only be taken when prescribed by
a physician or a P.A.
AREDS is the treatment of choice for “dry” AMD
Eating fresh fruits and dark green, leafy vegetables
Maintaining a low fat & low cholesterol diet
Exercising regularly
Wearing sunglasses with UV protection
Avoiding exposure to second-hand smoke
Getting an eye exam regularly
WET AMD: MANAGEMENT
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Laser photocoagulation
Photodynamic therapy
INVESTIGATIONAL TREATMENTS
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Submacular surgery
Retinal transplantation and transplantation of
RPE
Retinal translocation
Gene therapy
Angiogenesis inhibitors: like cytochalasin E,
Anecortave acetate, Prinomastat
Current Treatments for AMD
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Pegaptanib Sodium (MACUGEN®)
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Used to prevent further vision loss from wet AMD
Was first introduced in 2004
Was the first intravitreal injectable drug developed to treat wet AMD, and requires
monthly dosing
In the VISION (VEGF Inhibition Studies in Ocular Neovascularization) clinical
trials in 2003 and 2004, 70% of patients treated with a small dose of Macugen
(0.3mg) injected every 6 weeks had < 15 letters of vision loss at the primary end
point analysis, compared to only 55% of the control group
Macugen has less adverse effects and a
better safety profile than either laser
photocoagulation or PDT
Current Treatments for AMD
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Ranibizumab (LUCENTIS®)
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Approved by the FDA on June 30th, 2006
Intravitreal injection that requires monthly dosing
The only FDA-approved drug that not only drastically slows vision
loss due to AMD, but it also seems to actually restore some visual
acuity that has already been lost due to wet AMD destruction
In the MARINA study in 2004-2005 researching Lucentis, out of 716
patients enrolled, at 12 months 94.5% of the group given 0.3mg of
Lucentis and 94.6% of those given 0.5mg lost < 15 letters, as
compared with 62.2% of patients
receiving the control injections
Investigational Treatments for
AMD
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Bevacizumab (AVASTIN®)
 Avastin was approved by the FDA in February 2004 for the treatment
of metastatic colorectal cancer in combination with chemotherapy
 Incidentally, ranibizumab (Lucentis) is a chemically modified product
of bevacizumab (Avastin) that is affinity-matured to have a higher
affinity for VEGF, and it is made by the same laboratory, Genetech,
that also produces Avastin
 After initial results in 2005
from clinical trials with Lucentis
became available, ophthalmologists
began using Avastin to treat AMD
because of its similar chemical
structure to Lucentis
Investigational Treatments for AMD
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Avastin requires monthly intravitreal injections
Outcomes in patients treated thus far with Avastin have been
virtually identical to Lucentis, with no serious ocular effects
reported
It must be noted though that intravitreal treatment with
Avastin has not been proven effective and safe in controlled
clinical trials like Lucentis
TIPS FOR ARMD PATIENTS
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Monitor your vision daily with an Amsler grid
Take a multi-vitamin with zinc
Incorporate dark leafy green vegetables into
your diet
Always protect your eyes with sunglasses
that have UV protection
Quit smoking
Exercise regularly
Questions??
Thank you!!