Khodabande Farabi Eye Hospital TUMS Modifiable RFs Genetic bases Genetic testing to do or not to do Risk Score Risk Factors Development Progression NonModifiable RFs Age The number one ID: 932197
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Slide1
AMD Genetic / Risk Factors
KhodabandeFarabi Eye HospitalTUMS
Slide2Modifiable RFs ?
Genetic bases?Genetic testing, to do or not to do?
Risk Score?
Slide3Risk Factors
DevelopmentProgression
Slide4Non-Modifiable RFs
Slide5Age
The number one risk factor is age. One-third of adults over 75 are affected by AMD.
Slide6Gender
Females are more likely to develop AMD than males. This
factor may be because females live longer than males, and thus have more time to develop the disease.
Slide7Presence of AMD in One Eye
If a person has AMD in one eye, he or she is more likely to develop it in the other eye.
Slide8Race
Caucasians are more likely to develop AMD than other races. This factor may be related to differences in
genetic background or pigmentation.
Slide9Family History of AMD
A person is more likely to develop AMD if someone in his or her immediate family has had it.First degree
3 times
Slide10Eye Color
People with light-colored eyes are more likely to develop the dry type of AMD. This
factor may be because light-pigmented eyes offer less protection from damaging UV light.
Slide11Clinical Examination (AREDS 1)
Large drusen
Pigmentary changes (hypo, hyper, non central
GA
)
Score 0 / < 1%
Score 1 / 5%
Score 2 /12%
Score 3 / 25%
Score 4 / 50%
Slide12Modifiable
RFs
Slide13Smoking
Smoking causes oxidative damage, which may contribute to the development and progression of this disease.
two to five fold.
Slide14Diet
Avoid: Fat, Cholesterol and high glycemic index foods
Recommend : antioxidants and green leafy vegetables
Slide15High-glycemic index foods: white rice, bread and pasta
Low-glycemic foods: whole grain breads or oatmeal
Slide16AREDS 1 Conclusions
Persons older than 55 years should have dilated eye examinations to determine their risk of developing advanced AMD.
Increased intake of antioxidants and zinc
lowered the risk for disease progression by
25%
in patients with intermediate or advanced AMD
Slide172. Those with
extensive intermediate size drusenat least 1 large drusen
noncentral geographic atrophy
advanced AMD or vision loss due to AMD
and
without contraindications such as smoking
,
should
consider taking a supplement of antioxidants plus zinc such as that used in this study.
in 1 or both eyes
in 1 eye
Slide18AREDS2 / Primary goal:
if the addition of 10mg lutein
2mg zeaxanthin 1,000mg
omega-3
long-chain fatty acids (350mg DHA and 650mg EPA)
to the original AREDS formulation would further reduce the risk of progression to advanced AMD.
Slide19AREDS 2 Results
Omega-3 fatty acid supplementation did not yield a statistically significant reduction in the progression of AMD.
Addition of lutein, zeaxanthin to the AREDS formulation in primary analyses did
not
further reduce risk of progression to advanced AMD.
Slide20But….
Lutein and zeaxanthin have a role in AMD management, and should replace beta-carotene in the original AREDS formula.
Slide21Vitamin C
500 mgVitamin E 400
IUZn 80 mg
Lutein
10
mg
Zeaxanthin
2
mg
Slide22Prolonged Sun Exposure
Although the evidence is not conclusive, some studies suggest an association between AMD and cumulative eye damage from ultraviolet (UV) and other light.
Slide23Inactivity
In dry AMD, the retina does not receive adequate oxygen, leading to the death of cells in the macula. Exercise
improves cardiovascular health and might help prevent AMD.
Slide24Obesity
A person with a BMI of greater than 30 is 2.5 times more likely to develop the disease than a person with a lower BMI.
Slide25High Blood Pressure
High blood pressure, like smoking, leads to a constriction (narrowing) of the blood vessels that nourish the retina, restricting oxygen flow.
Slide26Slide27Family studies reporting increased risk of 2–3 fold among first-degree relatives of patients.
Increased monozygotic vs. dizygotic twin concordance.
Slide28Genetic and epidemiological research has established the undeniable role of genetic variation
in the etiology of AMD, with the heritable component estimated to be between 45% and 70% .
The odds ratio homozygous : between 3.5 and 7.4
Slide29q
arm,ch 1 : alternative complement system genes:
CFH gene, factor B (BF)/complement component 2 (C2),complement component 3 (C3
),
and complement factor I
q arm, ch10 :
ARMS2
and
HTRA1.
genes
involved in transporting and processing HDL (hepatic lipase C (
LIPC
) )
.
Tissue
inhibitor of metalloproteinase 3
(
TIMP3
)
:early-onset
form of macular degeneration known as
Sorsby's
fundus dystrophy
Slide30heterozygote : a
2.5-fold increase in developing AMDhomozygous : a six-fold
increase in developing AMD
Slide31CFH Non-neovascular AMD (GA)
ARMS2 Neovascular
AMD (CNV)
Slide32Awh
et al:No CFH risk alleles and with 1 or 2 ARMS2 risk
alleles derived maximum benefit from zinc-only supplementation.
Slide33One or two CFH
risk alleles and no ARMS2 risk alleles derived maximum benefit from antioxidant-only supplementation.Treatment with zinc was associated with
increased progression to advanced AMD.
Slide34Slide35Slide36Slide37Slide38Slide39Slide40Carl C.
Awh, MD
Emily Y. Chew, MD
Slide41Slide42AREDS
and AREDS2 supplements, remains the only proven beneficial formulation regardless of genotype.
Genetic testing is not recommended for initiating or determining the appropriateness of the AREDS formulation.
One should
not
deprive patients
of a therapy that has been proven
to have
significant public health impact on the basis of a
statistically flawed
, not replicated retrospective analysis of existing data
.
Slide43Genetic testing / Drawbacks
Until there is a true cure for AMD, knowing an individual’s risk factors may do little but worry a patient.
Telling a patient that he is at low risk based on our current knowledge may give them a
false sense of security
.
W
e
may be unnecessarily
frightening
our patients who may test at higher risk, but never develop the disease.
The
biggest downfall, some point out, may be that once this information is obtained, it could fall into the hands of
insurance
companies that provide medical, disability and life insurance.
Slide44Risk Scores
Risk scores have the potential to aid in evaluating the contribution of multiple factors to disease development and outcomes, progression, and response to treatment.
Slide45Slide46Take home messages
Modifiable RFs:Smoking cessationDiet low in fat, high in antioxidant
SupplementsWeight controlBlood pressure control
Exercise
CFH / GA ARMS2/ CNV
Genetic testing is
not recommended
for initiating or determining the appropriateness of the AREDS formulation.