Advances in the Treatment of

Age-Related Macular
Degeneration (AMD)
Michael E. Helm, PA-S
Spring 2007
Advisor: Sam Powdrill, MPhil, PA-C

What is AMD?
Age-related macular degeneration

(AMD) is defined as the loss of

macular function from the
degenerative changes of aging
The macula is the most important
part of the retina responsible for
sharp, central vision
AMD is divided specifically into
two distinct types: the less severe
or dry form, and the more severe
and debilitating wet form
The root causes of AMD are still

unknown

Who is at Risk for AMD?

AMD is the leading cause of irreversible vision

loss and blindness in persons over 65 years of age,

the fastest growing segment of the United States
population
Over a 5-year time span, it is estimated that 1 in 3
people over the age of 70 years will develop signs
of AMD
Caucasians > African Americans
Women > Men

What are the Risk Factors for AMD?

There are currently 5 specific risk factors that are

strongly associated with the development of

AMD:
1. Caucasian Ancestry
2. Genetic Component
3. Hypertension
4. Aging
5. Smoking
(SO QUIT NOW!!!!)

How is AMD Diagnosed?

As with many other medical conditions, the approach to

diagnosing AMD requires the integration of both the

patient history and the physical exam
Commonly patients will complain of visual symptoms
such as blurred or distorted vision, a need for increased
lighting, an increase in fatigue when reading, blind spots in
central vision, and reports of utility poles being curved or
bent when driving

How is AMD Diagnosed?

Along with the identification of the 5 known risk factors for AMD, a

dilated fundus exam remains the gold standard to definitively diagnose

the disease
Upon fundoscopic examination, patients with dry AMD usually only
display changes in the retinal pigment epithelium along with drusen
(yellow deposits under the retina)
Contrastly, patients with wet AMD display a green or dark red spot on
the macula itself
Results seen in Amsler grid
testing can also closely reveal
the location in the eye where
the damage from AMD has
mostly occurred

Preventative Approaches for AMD

Age-Related Eye Disease Study (AREDS) Formulation:
The specific daily amounts of antioxidants and zinc used by the study
researchers were 500 milligrams of vitamin C, 400 International Units
of vitamin E, 15 milligrams of beta-carotene (often labeled as
equivalent to 25,000 International Units of vitamin A), 80 milligrams
of zinc as zinc oxide, and two milligrams of copper as cupric oxide.
Copper was added to the AREDS formulation containing zinc to
prevent copper deficiency anemia, a condition associated with high
levels of zinc intake
This has been the standard of preventative
treatment for AMD since the AREDS
study was done in 2001

Preventative Approaches for AMD

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

Current Treatments for AMD

Laser Photocoagulation
Used to prevent further vision loss from wet AMD
Developed in the 1980s
Was the only available treatment for wet AMD prior to the 21st century
The laser procedure basically destroys the new, leaky blood vessels

that cause the substantial vision loss in wet AMD

This type of treatment for AMD
can be very destructive to the eye
itself if the laser is used too close
to the macula, causing immediate
and permanent vision loss

Current Treatments for AMD

Verteporfin Photodynamic Therapy (PDT)
Used to prevent further vision loss from wet AMD
Developed in 2000, this treatment uses a photoactivated drug,

Verteporfin, and an activating nonthermal laser

This was the first drug therapy developed for AMD
Verteporfin is a photoexcitable dye that is retained mainly in the wet
tissues of the retina and is activated by the light from the laser
Once activated, the drug thromboses
the new blood vessels in the area
and leads to a much slower rate of
vision loss in the AMD patient

Current Treatments for AMD

Pegaptanib Sodium (MACUGEN)
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

Ranibizumab (LUCENTIS)
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

Current Treatments for AMD

Mean increases in visual acuity were 6.5 letters in the

0.3mg group and 7.2 letters in the 0.5mg group, as

compared with a decrease of 10.4 letters in the control
injection group
Numbers seen in a similar study (ANCHOR) comparing
Lucentis against Verteporfin PDT were nearly identical to
the MARINA study, favoring Lucentis
Lucentis had no long-term effect on intraocular pressure,
and very few instances (<1%) of detached retina or uveitis
were reported
Endopthalmitis was also reported in <1% of the patients,
but this adverse effect was concluded to be caused by the
injection procedure alone

Investigational Treatments for AMD

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

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

Barriers to AMD Treatment

Most Treatments are EXPENSIVE!!!!!
Macugen = ~$900 per injection (per eye)
Lucentis = ~$1,950 per injection (per eye)
In the United States, under Medicare, Macugen

or Lucentis is covered through Part B; patients are

responsible for a 20% co-payment for each injection
This would still require nearly $400 per month (or $800 if
both eyes were significantly affected) that the patient
would be required to pay out-of-pocket per injection,
unless they had a Medicare supplemental insurance or
qualified for a support program like Medicaid

A More Affordable Option?

Avastin
Not nearly as expensive as drugs specifically

designed for treatment of AMD

~$6 $10 per injection (per eye)
Already is used widely by ophthalmologists
around the world
However, it does not have randomized, clinical
trials to back up the efficacy and safety of its use
in AMD

A More Affordable Option?

Fortunately, most national insurance carriers cover

intravitreal injections of Avastin, given with the patients

informed consent, just as they do Lucentis even though a
national policy supporting this practice has never been
officially adopted
Currently, there appears to be a global consensus that the
treatment strategy using intravitreal Avastin is logical, the
potential risks to patients are minimal,
and the cost-effectiveness is so obvious
that the treatment should not be withheld
due to lack of clinical trial evidence
(Rosenfeld, 2006)

Conclusion
While AMD continues to afflict a vast number of

individuals over the age of 65 each year, treatments are now

being utilized that finally counteract the most debilitating
aspects of this disease
It is imperative for people who are at risk for developing
AMD to understand preventative measures they can employ
such as implementing smoking cessation and controlling
hypertension which can have huge impact on the initial
development of the disease
Recognize as primary care providers that AMD is seen
commonly in practice today, and there are now methods of
treatment that can be used to help these patients
Do not hesitate to refer
to an ophthalmologist for tx!!!!

References

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Accessed November 10, 2006.

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Questions??

Thank you!!