Download I. Wet Macular Degeneration

The lecture will include many photographs and OCT scans of non-exudative and
exudative macular degeneration. All photographs are of patients evaluated at
the Grand Rapids VA.
I.
Macular Degeneration
A.
Discussion of Macular Degeneration
1. Epidemiology
a) Most Frequent Cause of Severe Central visual Loss in people over 50 in
developed countries
b) Vision loss occurs when the RPE atrophies and results in the secondary
loss of the overlying photoreceptor that it supplies
c) Majority of eyes that develop severe visual loss do so because of the
development of choroidal neovascularization.
d) Age predilection
e) Often bilateral
f) More prevalent in Caucasians and likely has a more severe course in
patients who have light-colored eyes
g) Probable genetic Component
2. Pathophysiology
a) All forms of AMD possess initial, common changes within the macular
RPE. While the mechanisms and processes are poorly understood,
some postulate these changes are initiated by isolated regions of
choriocapillaris vascular failure. These proceedings cause the RPE to
degenerate, resulting in photoreceptor loss. As the photoreceptors
disintegrate, the inner nuclear layer collapses and contacts Bruch’s
membrane, initializing the degeneration of the outer retinal layers.
Some theorize that the mechanism of damage may be through
ultraviolet radiation-induced oxidation and free radical formation within
these structures
B.
Types of Macular Degeneration
1. Non-exudative (dry) macular degeneration
2. Exudative (wet) macular degeneration
a)
C.
Symptoms of ARMD
1. Symptoms Range from None to Severe
2. Blurred Vision
3. Metamorphopsia
4. Decreased Reading Ability
5. Trouble with Dark Adaptation
6. Symptoms are typically gradual, but may be sudden in cases of exudative macular
degeneration.
D.
Early Signs of Macular Degeneration
1. Drusen
a)
b)
c)
d)
Widely variable in size
May disappear with time
Can occur anywhere in the fundus
Focal, whitish-yellow deposits of eosinophilic materal between the
basement membrane of the RPE and Bruch’s Membrane
e) Drusen outside the macula do not affect vision
f) Almost always present in early macular degenerationAlone, they do
not cause vision loss but they are a risk factor for geographic atrophy
and choroidal neovascularization.
2. Dry ARMD
a) Funduscopic examination is significant for drusen in the early stages of
disease. These drusen usually are confluent with significant pigment
changes and accumulation of pigment in the posterior pole. RPE often
appears atrophic with an easier visualization of the underlying
choroidal plexus
E.
Geographic Atrophy
1. In advanced stages of dry AMD, these focal islands of atrophy coalesce
and form large zones of atrophy with severely affected vision
2. When the dry form of AMD progresses with larger areas of RPE atrophy, the
condition is referred to as geographic atrophy
a)
F.
Prevention
1. UV Protection – Hat, Sunglasses
2. Multivitamin with Lutein
3. Green, leafy vegetables (as long as patient is not taking Coumadin)
4. AREDS vitamin supplement for select cases
G.
Wet Macular Degneration
1. About 10-15% of macular degeneration cases are the wet or exudative
form, in which newly-formed, immature blood vessels grow from the
choroid (choroidal neovascularization) and leak into the spaces above and
below the retinal pigment epithelium (RPE).
2. Wet AMD results when the macular RPE/Bruch’s barrier is compromised by
new, weak and leaky blood vessels that grow upward into the retina from
the choriocapillaris. These occult (poorly defined) or classic (more easily
defined) subretinal choroidal neovascular membranes may leak
serosanguinous fluid causing RPE detachment, sensory retinal
detachment, subretinal or intraretinal bleeding or fibrovascular, disciform
scarring.
H.
Risk of Progression
1. In general, the risk to patients with dry AMD for progression to wet AMD,
over any given five-year period, is approximately 14 to 20 percent.
2. In patients who have already lost one eye to wet AMD, over the course of five years,
the risk of developing wet stage disease in the fellow eye is 10 percent for patients
whose fellow eye has neither large drusen or pigment clumps, 30 percent for fellow
eyes containing either large drusen or pigment clumps and 50 percent for fellow eyes
with both pigment clumps and large drusen present.
I.
Wet Macular Degeneration
1. Subfoveal wet AMD is divided into three principal subtypes based on the
pattern of the abnormal blood vessels, or lesions, as seen in the retina
through an fluorecein angiography.
a) The classic pattern consists of well-defined abnormal blood vessels
with distinct edges. In the occult pattern, the edges of the abnormal
blood vessels are more poorly demarcated and diffuse. The principal
subtypes of subfoveal wet AMD, based on the patterns of the abnormal
blood vessels, are the following:
(1) Predominantly Classic. In the predominantly classic subtype, it is
estimated that this subtype accounts for approximately 25% of the
cases of subfoveal wet AMD and generally has the most aggressive
disease pathology, leading to more rapid vision loss than the other
subtypes.
(2) Minimally Classic. In the minimally classic subtype, it is estimated that this
subtype accounts for approximately 35% of the cases of subfoveal wet AMD
and generally has a less rapid rate of vision loss than the predominantly
classic subtype, but a more rapid rate than the occult subtype.
(3) Occult. In the occult subtype, all of the patient's abnormal blood vessels are
of the occult pattern. It is estimated that this subtype accounts for
approximately 40% of the cases of subfoveal wet AMD and generally has a
less rapid rate of vision loss.
J.
Treatments for Wet ARMD
1. Argon or Diode Laser Focal Treatment
2. Best if CNVM located away from fovea
3. Photodynamic Therapy
4. Best on Classic CNVM
5. 30-40% of patients still experience vision loss
6. Sometimes combined with steroid injection
7. Anti-VEGF Injections
K.
Anti-VEGF Treatment
1. Becoming the standard first-line therapy
2. Macugen and Lucentis are FDA approved to treat wet macular degeneneration
3. Avastin use is off-label
a) Significantly lower cost
b) Was briefly taken off the market by manufacturer so they could make
more money with Lucentis
L.
VEGF
1. VEGF is a protein in the eye which encourages the development of blood
vessels
2. Anti VEGF drugs inhibit VEGF by trapping it or preventing it from binding with
elements which will stimulate growth
3. Research is currently focused on strategies to optimize treatment delivery
M.
Studies Involving VEGF
1. MARINA and ANCHOR Trials
a) Monthly Injections of Lucentis
b) Results were Excellent
c) Such a schedule is not generally feasible, because it is timeconsuming, costly, and increases the risk of side effects from injection
2. PIER study
a) Sought to address the dosing frequency issue
b) 3 monthly doses followed by quarterly injections for the next 21
months
c) Mixed Results
d) Patients experienced a maximum increase in visual acuity and a
decrease in retinal thickness after the 3 initial doses, but then had
some decrease of benefits during the quarterly dosing regime
e) Overall, treated patients experienced better outcomes than control
patients but the results were not as impressive as those seen from the
monthly dosing of the MARINA and ANCHOR trials.
3. PrONTO study
a) Designed to reduce treatment frequency by establishing 5 criteria that
include FA and OCT for re-treatment with ranibizumab
(1) Loss of ≥ 5 ETDRS letters with OCT evidence of macula edema
(2) Increased central retinal thickness of ≥ 100 micrometers (mcm) on OCT
(3) New macular hemorrhage
(4) New area of classic CNV seen on FA
(5) Persistent fluid on OCT at least 1 month after the previous injection.
(6) The amount of testing performed in PrONTO may not be practical in a busy
clinic, and modified criteria are often used by practicing clinicians.
N.
The "treat and extend" method
1. Patients are instructed to return 6 weeks after receiving 3 initial monthly
injections of ranibizumab
2. At the 6-week follow-up visit, patients receive an injection
3. If there is no hemorrhage or exudation on bimicroscopy or OCT, they are asked to
return in 8 weeks for an examination and injection. But if there are exudative
changes, they are instructed to return in 4 weeks
4. In essence, for every visit in which patients do not show persistent or new exudative
changes, their follow-up injection is extended by 2 weeks. If changes are seen,
patients are asked to shorten the next visit interval by 2 weeks
5. Treatments are never more frequent than 4 weeks
O.
Treatment Standards
1. There is no clearly established anti-VEGF treatment standard
2. Most retinal specialists have their own methods
3. OCT is emerging as an important tool for treatment indication
4. FA is being used less frequently for follow-up
5. OCT is sometimes fooled by falsely representing the macular thickness (Its not
perfect)
P.
Disciform Scarring
1. Choroidal neovascularization usually results in serous or hemorrhagic
detachment of the RPE or sensory retina, eventually accompanied by
fibrous tissue with RPE proliferation and atrophy. This end-stage condition
is referred to as disciform scarring.
Q.
Other Causes of CNVM
1. Angiod Streaks
2. Best’s Disease
3. Fundus flavimaculatus
4. Idiopathic
5. Histoplasmosis
6. Optic Disc Drusen
7. Progressive Myopia
8. Photcoagulation
9. Sarcoidosis
10. Traumatic Choroidal Rupture
R.
Age-Related Eye Disease Study (AREDS)
1. The Age-Related Eye Disease Study (AREDS) - sponsored by the Federal
government's National Eye Institute - has found that taking high levels of
antioxidants and zinc can reduce the risk of developing advanced agerelated macular degeneration (AMD) by about 25 percent.
2. This major clinical trial closely followed about 3600 participants with varying stages of
AMD. The results showed that the AREDS formulation, while not a cure for AMD,
may play a key role in helping people at high risk for developing advanced AMD keep
their remaining vision
3. Who should take the combination of antioxidants and zinc like those used in the AgeRelated Eye Disease Study?
a) People who should consider taking the combination of antioxidants
plus zinc include those who are at high risk for developing advanced
AMD. These people are defined as having either:
(1) Intermediate AMD in one or both eyes. Intermediate AMD is
defined as the presence of either many medium-sized drusen or
one or more large drusen.
(2) Advanced AMD in one eye, but not the other eye. Advanced AMD is defined
as either a breakdown of light-sensitive cells and supporting tissue in the
central retinal area (advanced dry form), or the development of abnormal and
fragile blood vessels under the retina (wet form) that can leak fluid or bleed.
Either of these forms of advanced AMD can cause vision loss.
4. AREDS Medications
a) These should be considered a drug
b) Smokers should use smokers formula secondary to risk of lung cancer
(removes Beta-carotene and substitutes Lutein)
c) Should consult primary care physician before starting
S.
AREDS2
1. The objectives of AREDS2 are to:
a) Study the effects of high supplemental doses of the dietary
xanthophylls (lutein and zeaxanthin) and omega -3 LCPUFAs (DHA and
EPA) on the development of advanced AMD.
b) Study the effects of these supplements on cataract and moderate vision loss
(doubling of the visual angle or the loss of 15 or more letters on the ETDRS
chart).
c) Study the effects of eliminating beta-carotene in the original AREDS formulation
on the development and progression of AMD.
d) Study the effects of reducing zinc in the original AREDS formulation on the
development and progression of AMD.
2. Validate the fundus photographic AMD scale developed from the Age-Related Eye
Disease Study.
II.
Reading References
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