Download Advances in the Treatment of Age-Related Macular Degeneration

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
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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 1980’s
 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
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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 patient’s
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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Expert Opin Emerg Drugs 2006; 11(4): 725-740.
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Exp Eye Res 2006; 83(3): 615-619. http://www.nei.nih.gov/health/maculardegen/armd_facts.asp.
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Questions??
Thank you!!