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Age-related macular degeneration (AMD) is the leading cause of irreversible blindness.The disease adversely affects quality of life and activities of daily living, causing many affected individuals to lose their independence in their retirement years. - PowerPoint PPT Presentation
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Age-related macular degeneration (AMD) is the
leading cause of irreversible blindness.The disease
adversely affects quality of life and activities of daily
living, causing many affected individuals to lose their
independence in their retirement years.
Despite the introduction of new therapies for
prevention and treatment of AMD, the prevalence of
AMD is expected to increase by 97% by the year
2050.
The only proven treatment available for the dry or
nonexudative forms of this disease, comprising
85% of cases, is an antioxidant/mineral supplement
which can slow the progression of the disease by
25% over 5 years.
For the wet form of the disease, anti-
vascular endothelial growth factor
(VEGF) treatments have been very
effective in preventing severe vision loss.
Classification
Macular degenerative changes have typically been
classified into two clinical forms, dry or wet, both of which
can lead to visual loss.
In the early or intermediate dry forms visual loss is
infrequent, and when it occurs it is usually gradual.
Ophthalmoscopy reveals yellow subretinal deposits called
drusen, or retinal pigment epithelial (RPE) irregularities,
including hyperpigmentation or hypopigmentary changes.
Larger drusen may become confluent and evolve into
drusenoid RPE detachments. These drusenoid RPE
detachments often progress to geographic atrophy and less
frequently to neovascular AMD.
In the wet form, vision loss can appear to occur suddenly,
when a choroidal neovascular membrane leaks fluid or blood
into the subpigment epithelial or subretinal space. Serous RPE
detachments with or without coexisting choroidal
neovascularization (CNV) are also classified as the wet form.
Quality of life
More recently in one study of well-being, patients with AMD had
lower scores than patients with chronic obstructive pulmonary
disease and acquired immunodeficiency syndrome (AIDS); the
lower quality of life in patients with AMD was related to greater
emotional distress, worse self-reported general health, and greater
difficulty carrying out daily activities.
Not only is AMD associated with a higher rate of
depression in the community-dwelling adult population
when compared to the unaffected adult population,but
depression also exacerbates the effects of AMD.
Risk Factors
1. Age 8. Cup-to-disc ratio 15. Cardiovascular diseases
2.Gender 9. smoking 16. Blood pressure and hypertension
3. Race / ethnicity 10.Antioxidants,vitamins, and minerals
17. Cholesterol levels and dietary fat intake
4. Socioeconomic status 11. Alcohol intake 18. Diabetes and
hyperglycemia
5. Refractive error 12. Obesity and physical activity
19. Hormonal and reproductive factors
6. Iris color 13. Sun light exposure 20. Inflammatory factors
7.Lensopacities,cataracts, and cataract surgery 14. Medications 21. Genetic factors
Antioxidants, vitamins, and minerals
The role of antioxidant vitamins in the pathogenesis of AMD
has received a great deal of attention. Antioxidants, which
include vitamin C (ascorbic acid), vitamin E (alpha-tocopherol),
and the carotenoids (including alpha-carotene, beta-carotene,
cryptoxanthin, lutein, and zeaxanthin), may be relevant to AMD
because of their physiologic functions and the location of some
of these nutrients in the retina.
Lutein and zeaxanthin, in
particular, are associated
with macular pigment.
Trace minerals such as zinc, selenium, copper, and
manganese may also be involved in antioxidant
functions of the retina.
Antioxidants could prevent oxidative damage to
the retina, which could in turn prevent
development of AMD.
Damage to retinal photoreceptor cells could be
caused by photo-oxidation or by free radical-
induced lipid peroxidation.This could lead to
impaired function of the RPE and eventually to
degeneration involving the macula.
The deposit of oxidized compounds in healthy tissue
may result in cell death because they are indigestible by
cellular enzymes. Antioxidants may scavenge,
decompose, or reduce the formation of harmful
compounds.
The AREDS confirmed that antioxidant and zinc
supplementation can decrease the risk of AMD
progression and vision loss. This study included a
double-blind clinical trial in 11 centers around
the USA, randomly assigning 3640 participants to
take daily oral supplements of antioxidants, zinc,
antioxidants and zinc, or placebo.
Both zinc alone and antioxidants and zinc
together significantly reduced the odds of
developing advanced AMD in participants
with intermediate signs of AMD
The zinc supplement included zinc (80 mg)
as zinc oxide, and copper (2 mg) as cupric
oxide; the antioxidant supplement included
vitamin C (500 mg), vitamin E (400 IU), and
beta-carotene (15 mg).
If the AREDS formulation were used to treat the 8
million individuals in the USA who are at
increased risk for developing advanced AMD, the
AREDS group authors estimate that more than
300,000 would avoid advanced AMD and the
associated vision loss during the next 5 years.
AREDS-type supplements are a cost-effective way of
reducing visual loss due to the progression of AMD.
The effect of dietary antioxidants on the incidence of
early AMD has not been established and there are
questions about the effect of beta-carotene
supplements on AMD since there is none in the
retina, and high doses of zinc could have side-
effects.
Diets high in antioxidant-rich fruits and vegetables may
be related to a lower risk of exudative AMD. The first
study launched to evaluate diet and AMD, the Dietary
Intake Study, ancillary to the EDCCS, showed an inverse
association between exudative AMD and dietary intake
of carotenoids from foods.
In that study reported in 1994, a diet rich in green
leafy vegetables containing the carotenoids lutein and
zeaxanthin was associated with a reduction in the risk
of exudative AMD.
A prospective double-masked study involving lutein and
antioxidant supplementation in a group of 90 individuals
showed that visual function was improved with 10 mg of
lutein or a lutein/antioxidant formula.
In a British study of 380 men
and women, lower plasma
levels of zeaxanthin were also
found to be associated with an
increased risk of AMD.
A cross-sectional study using
previously collected NHANES I data
found a weak protective effect with
increased consumption of fruits
and vegetables rich in vitamin A.
A prospective follow-up study has shown
that fruit intake is inversely associated with
exudative AMD.
AREDS2, an ongoing trial of lutein, zeaxanthin, and
omega 3 fatty acids and assessment of omission of beta-
carotene and use of much lower doses of zinc for the
prevention of AMD progression, may provide additional
data regarding optimal vitamin supplement regimens for
AMD patients.
Age
All studies demonstrate that the prevalence, incidence, and
progression of all forms of AMD rise steeply with increasing
age. There was a 17-fold increased risk of AMD comparing
the oldest to the youngest age group in the Framingham
Study.
Gender
Several studies have shown no overall difference in the
frequency of AMD between men and women, after
controlling for age. However, in NHANES III, men,
regardless of race and age, had a lower prevalence of AMD
than women.
Race/ethnicity
Overall, the literature to date suggests that early AMD is
common among blacks and Hispanics, although less common
than among non-Hispanic whites, whereas advanced AMD is
much less common in these groups compared with non-
Hispanic whites. Furthermore, differences in prevalence rates
between non-Hispanic whites in different regions of the USA
suggest that ethnicity is an important determinant of AMD.
Socioeconomic status
Less education and lower income have been shown to be
related to increased morbidity and mortality from a
number of diseases, and there are mixed findings for AMD.
Furthermore, no associations were noted in another
case–control study or in the FES, although different
definitions of macular degeneration were used in those
reports, compared with the more recent studies. It is
possible that education is a surrogate marker for
behaviors and lifestyles related to AMD.
Refractive error
Several case–control studies have shown an association
between AMD and hyperopia.
This association, therefore, might implicate
structural and mechanical differences that render
some eyes predisposed to maculopathy.
Iris color
Higher levels of ocular melanin may be protective against light-
induced oxidative damage to the retina, since melanin can act as
a free radical scavenger and may have an antiangiogenesis
function.
Lens opacities, cataracts, and cataract surgery
Data regarding the relationship between cataracts and AMD are inconsistent. FES investigators found no relationship, whereas data from the NHANES did support a relationship between AMD and lens opacities. In the BDES, in which photographs of the lens and macula were graded, nuclear sclerosis was associated with increased odds of early AMD (OR 1.96; 95% CI 1.3–3.0) but not of late AMD. Neither cortical nor posterior subcapsular cataracts were related to AMD. A case–control study of 1844 cases and 1844 controls indicated that lens opacities or cataract surgery were associated with an increased risk of AMD.
Although AMD-affected individuals reported better
visual function and quality of life after cataract
surgery, a history of cataract surgery has been found
to be associated with an increased risk for advanced
AMD in some earlier studies. Investigators have
postulated that this association might arise because
the cataractous lens can block damaging ultraviolet
light.
Inflammatory changes after cataract surgery may also
cause progression of early to late AMD. In the BDES,
previous cataract surgery at baseline was associated with
a statistically significant increased risk for progression of
AMD (OR 2.7) and for development of late AMD
In the BDES, previous cataract surgery at baseline was
associated with a statistically significant increased risk for
progression of AMD (OR 2.7) and for development of late
AMD .
In more recent prospective studies, however, including the
large AREDS study cohort, there was no evidence to support a
higher rate of progression of AMD in patients who underwent
cataract surgery.
Cup-to-disc ratio
The EDCCS demonstrated that eyes with larger cup-to-disc
ratios had a reduced risk of exudative AMD. This effect
persisted even after multivariate modeling, adjusting for
known and potential confounding factors.
Smoking
The preponderance of epidemiologic evidence indicates a
strong positive association between both wet and dry AMD
and smoking.
Smoking is an important, independent,
modifiable risk factor for AMD.
Mechanisms by which smoking may increase the risk of
developing AMD include its adverse effect on blood lipids
by decreasing levels of high-density lipoprotein (HDL) and
increasing platelet aggregability and fibrinogen,
increasing oxidative stress and lipid peroxidation, and
reducing plasma levels of antioxidants.
Alcohol intake
Studies that have examined the relationship between AMD
and alcohol consumption have yielded mixed results.
In the EDCCS, no significant relationship
between alcohol intake and exudative AMD
was noted in univariate analyses.
In a case–control study using
NHANES I data, moderate wine
consumption was associated with a
decreased risk of developing AMD.
In a large prospective study, no support was found for a
protective association between moderate alcohol
consumption and risk of AMD, although there was a
suggestion of a modest increased risk of AMD in heavier
drinkers.
The evidence to date suggests that alcohol intake does
not have a large effect on the development of AMD.
Obesity and physical activity
There is an association between AMD and overall
obesity and abdominal adiposity.
Obesity and physical activity are modifiable factors
that may alter an individual's risk of AMD incidence
and progression.
Sunlight exposure
The literature to date regarding the association between
sunlight exposure and AMD is conflicting. Overall, the data
do not support a strong association between ultraviolet
radiation exposure and risk of AMD, although a small effect
cannot be ruled out.
Medications
Some studies have shown borderline statistically
significant associations between increased risk of early
AMD with use of antihypertensive medication, especially
beta-blockers.
Other studies have shown a decreased rate of CNV
among AMD patients taking aspirin or cholesterol-
lowering drugs such as statins.
Cardiovascular diseases
Some studies have suggested an association between
AMD and clinical manifestations of cardiovascular disease
(CVD).
Blood pressure and hypertension
The role of blood pressure in the etiology of AMD remains
unclear.
Cholesterol levels and dietary fat intake
There is some evidence linking cholesterol level to AMD,
but not all results are consistent.
A case–control study showed that higher HDL
cholesterol levels tended to reduce the risk of
AMD.
Dietary fat intake was associated with an elevated
risk of exudative AMD in the Dietary Ancillary
Study of EDCCS.
A high intake of fish and omega-3 fatty acids reduced the
risk when linoleic acid intake was low.
Nuts have also been shown to decrease the risk of AMD
progression.
Diabetes and hyperglycemia
Many studies have investigated the relationship between
diabetes and/or hyperglycemia and AMD, and most have
found no significant relationships.
One difficulty with these studies is the uncertainty of
diagnosing AMD in the presence of diabetic retinopathy.
Also, many studies of AMD exclude persons with
diabetic retinopathy.