fafaf

1. Advances in the Treatment of
Age-Related Macular
Degeneration (AMD)
Michael E. Helm, PA-S
Spring 2007
Advisor: Sam Powdrill, MPhil, PA-C

2. 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 c
‘dr ” form, and the
more severe and debilitating
“wet” form
The root causes of AMD are
still unknown
Matular’De’generation

3. 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

4. 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 NO

5. 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 disto<ed vision, a need for increased
lighting, an increase in fatigue when redding, blind spots in
central vision, and reports of utility poles being curved or
bent when driving

6. 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 pen or dark red spot on
the rnacula itself
Results seen in Amsler grid
testing can also closely reveal
the location in the eye where
the damage from AMD has
mostly occurred

7. Preventative Approaches for AMD
Ace-Related E e Disease Stud AREDS Formulation:
The specific daily amounts of antioxidants and zinc used by the
study researchers were 500 milligi'ams 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), SOmilligrams
of zinc as zinc oxide, and two milligrams of cover 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

8. 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

9. Current Treatments for AMD
Laser PhotocOaRÏllation
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 subStàntÍàl ViSÍOii 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

10. Current Treatments for AMD
Verte orfin Photod namic Thera PDT
Used to prevent further vision loss from wet AMD
Developed in 2000, this ti'eatment uses a photoactivated drug,
Verteporfin, and an activating nonthermal laser
This was the first drug therapy developed for AMD
Veueporfin 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

11. Current Treatments for AMD
Pe tanib Sodium MACUGEN&
Used to prevent further vision loss from wet AMD
Was first introduced in 2004
Was the first intraviweal 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, 70Rr of patients
treated with a small dose of Macugen (8.3mg) injected every 6 weeks
had < 15 letters of vision loss at the primary end point analysis,
compared to only 55Rc of the control group
Macugen has less adverse effects
and a better safety profile than either
laser photocoagulation or PDT

12. Current Treatmentsfor AMD
Ranibizumab LUCENTIS49
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

13. 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 <l % of the patients,
but this adverse effect was concluded to be caused by the
injection procedure alone

14. Investigational Treatments for
AMD
Bevacizumab AVASTINO
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
Atter 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

15. 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

16. 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

17. 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

18. 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)

19. 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!!!!

20. References
1. Augustin AJ, Offermann l. Emerging drugs for age-related macular degeneration.
Expert Opin Emetg 0rc/gs 2006: 11(4): 725 740.
2. Bashshur ZF, Bazarbachi A, Schakal A, Haddad ZA, El Haibi CP, Nouraddin BN
lntravitreal bevacizumab for the management of choroidal neovascularization in
age related macular degeneration. Am J Opthalmol 2006; 142(1): 1-9.
3. Brown DM, Kaiser PK, Michels M, Soubrane G, Heier JS, Kim RY. et at.
Ranibizumab versus verteporfin for neovascular aqg-related macular
degeneration. // Eng/ /Ued2006; 355(14): 1432-1444.
4. D'Amico DJ, Patel M, Adamis AP, Cunningham ET Jr, Guyer DR, Katz B.
Pegaptanib sodium for neovascular age-related macular degeneration:
two-year safety resuks of the two prospective, multicenter, controlled clinical
tnals. Opthalmology 2006, 113f6): 1001.e1-6,
5. Eter N, Krohne TU, Holz FG. New pharmacologic approaches to therapy for
age-related macular degeneration. Biodrugs 2006; 20(3): 167-179.
6. Freeman WR, Falkenstein 1. Avastin and new treatments for AMD: where are we?
Retina 2O06; 26(8): 853-858.
7. Heier JS, Antoszyk AN, Pavan PR, Leff SR, RosenJald PJ, Ciulla TA, et al.
Ranibizumab for treatment of neovascular age related macular degeneration: a phase l/l1 multicenter, controlled, multidosa study.
Opthalmology 2006: 113(4): 642.e1-4.
8. Kourlas H, Schiller DS. Pegaptanib sodium for the treatment of neovascular
age-related macular degeneration: a review. Clin Ther 2006: 28(1): 36-44.
9. Michels S, Schmidt-Ei1urth U, Rosenfeld PJ. Promising new treatments for
neovascular age-related macular degeneration. Expert Opi'n Investing Dru9•
2006: 15(7): 779-793.
10.National Institutes of Health, National Eye Institute. Age-related macular
degeneration. November 2006. Available at.
macular degeneration.
Exp Eye Yes 2006; 83{3). 615-619. hip '’/wwy nei nih gov'’health'’’macuIardegen.’armd facts asp.
Accessed November 10, 2006

21. References
1. Ng EW, Adamis AP. Targeing angiogenesis, the underlying disorder in neovasculaf
age related macular degeneration. Can J Opthalrnol 2005; 40(3): 352-368.
12. Pieramici DJ, Avery RL. Ranibizumab: treatment in patients with neovascular
age-related macular degeneration. Expert Opin Emerg Drugs 2006. 6(11):
1237-1245.
13. Rosenfeld PJ. Intravitreal avastin. the low cost alternative to lucentis? Am J
Opthalmol 2006; 142(1): 141-143.
14. Rosenfeld PJ, Brown DM, Heier JS, Boyer DC. Kaiser PK, Ghung CY, et al.
Ranibizumab for neovascular age-related macular degeneration. N Engl J Med
2006: 355(14). 1419-1431.
15. Slakter JS. Anecortave acetate for treating or preventing choroidal
neovascularization. Opthalmol Cli'n North Am 2006;19{3): 373-380.
16. Spaide RF, Laud K, Fine HF, Klancnik JM Jr, Meyerle CB, Yannuzzi LA, et al.
lntravitreal bevacizumab treatment of choroidal neovascularization secondary to age related macular degeneration. Retina 2006;
26(4)! 383-390.
17. Steinbrook R. The price of sight—‹anibizumab, bevacizumab. and the treatment of
macular degeneration. // El gl J Med 2006: 355(14): 1409-1412.
18. Vavvas D, D'Amico DJ. Pegaptanib (Macugen): treating neovascular age-related
macular degeneration and current role in clinical practice. Opthalinol Clin
North Am 2006; 9(3): 353-360.
19. Wiggins MN, Uwaydat gH. Age-related macular degeneration: options for earlier
detection and improved treatment. J Fain Pract 2006; 55{1): 22-27.
20. Zhou B, Wang B. Pegaptanib lor the treatment of age related

22. Questions??
Thank you!!