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Macular
Degeneration
Age-related macular degeneration (AMD) is the major cause of severe
vision loss in people over age 60. There is currently no cure, but
in some cases the progression of the disease can be slowed.
What is the macula?
The macula is at the back of the eye, the bull's eye center of
the retina. It is the part of the eye that allows us to see fine
details such as the numbers on a watch, the features on someone's
face, or the amount of spices poured from a container. People with
macular degeneration still retain peripheral vision, but lose the
ability to see details.
Risk Factors
Risk factors for getting macular degeneration include age (over
50), heredity, smoking, excessive alcohol intake, light skin and
blue eyes.
Symptoms
The first sign of macular degeneration may be the appearance of
spots, called drusen, in your vision. You may notice some distortion
in straight lines. The dotted lines down the center of the road,
for instance, may seem crooked or the doorframe may appear warped.
If you notice these changes in vision, or if colors look different
to each eye, see your eye doctor promptly for an evaluation. Early
detection is important for effective treatment.
There are two forms of macular degeneration, "dry" or
atrophic, and "wet." Approximately 85-90 percent of people
with macular degeneration have the dry form.
Dry AMD
Drusen (spots) on the macula that are present for a long time may
cause the macula to thin out and stop working, or atrophy. This
is considered the dry form of AMD, and causes slow, progressive
vision loss. There is no medical or surgical treatment for dry AMD,
but there are many low-vision tools that can assist with daily living.
Click here for information about
the Low-Vision Center. People with dry macular degeneration
in one eye may be able to function very well using the central vision
from the other eye. Even in cases where dry AMD affects both eyes,
enough peripheral vision is usually retained to be able to continue
activities that don't require fine vision.
The dry form of AMD can change into the wet form, which is much
more severe. It is very important that people with dry AMD monitor
vision daily with an Amsler grid and report any changes to the eye
doctor.
1) "Normal" view of Amsler grid shows straight lines
2) Macular degeneration causes the lines to appear distorted
Wet AMD
In the wet form of AMD, abnormal blood vessels grow under the macula
and leak fluid and blood. The abnormal vessels, called subretinal
neovascularization, may also lift up the retina. In some cases,
if diagnosed early enough, laser surgery can seal the leaking blood
vessels, minimizing vision loss. Laser treatment does not improve
vision, it merely stops further deterioration and does not work
all the time. Successful treatment is in large part determined by
how early the problem is treated and the location of the abnormal
blood vessels. In some cases the abnormal blood vessels will stop
growing and leaking for at least one year. It is quite possible,
however, that additional abnormal blood vessels will grow elsewhere
in the eye after surgery. Your doctor will determine whether you
are a good candidate for laser surgery after doing a thorough examination
using digital imaging or indocyanine green angiography.
New Strategies for Treating Macular Degeneration
by Peter E. Liggett, M.D.
Researchers and clinicians around the country are putting a great
deal of effort into developing other strategies and new technologies
for treating AMD. Many are still in the development stage, but may
be promising in the near future. Some of these include:
Photodynamic Therapy
Prophylactic Treatment of AMD
Retinal Translocation
External Beam Irradiation
Gene Transfer
New Drug Therapies
How does PDT Work?
PDT is a generic term to describe a type of treatment using photosensitizing
drugs. We will provide a general description of how PDT works, but
for details on each drug, please click on the individual pages below
or visit the developers' websites.
PDT employs a photosensitizing drug (a drug that is "activated"
when exposed to light) that is injected into the patient's arm and
circulates to the abnormal blood vessels. The doctor then focuses
an extremely low-energy red laser beam through the pupil of the
eye onto the leaky vessels, activating the drug, which destroys
the abnormal vessels. The objective is to destroy the abnormal blood
vessels while preserving neighboring healthy blood vessels and tissue.
Prophylactic Treatment of Age-Related
Macular Degeneration (PTAMD)
Since wet AMD presents a serious threat of vision loss, it makes
sense to try to prevent dry AMD from developing into wet AMD. A
preliminary study, led by Dr. R. Joseph Olk, and published in the
November 1999 issue of Ophthalmology, found that prophylactic laser
treatment of eyes with dry AMD, in some cases, causes a reduction
in size or complete disappearance of drusen, the yellow spots that
develop under the retina. The ophthalmic literature reports some
evidence that disappearance of drusen can, in some cases, lead to
improvement of vision and a slowing down of the development of the
abnormal blood vessels that characterize wet AMD.
A nationwide clinical trial, called PTAMD, is now underway in 21
centers, including New England Retina Associates, to confirm the
pilot study results and to prove that this treatment can decrease
or delay the development of abnormal blood vessels and the associated
severe visual loss. Click here for more information about the PTAMD
trial or to find out the participation criteria.
Retinal Translocation
The technique of retinal translocation has the potential for restoring
central visual function in certain patients with subfoveal neovascular
AMD. This surgical procedure moves subfoveal neovascular membranes
away from the fovea in an attempt to maintain the function of the
sensory retina and preserve central vision.
We have used this technique in several patients with subfoveal
neovascular membranes. In three patients' we improved the vision
from 1/200 to 20/100, 1/400 to 20/200, and one patient which had
1/400 vision with no improvement. Complications included the development
of cataract in all patients, and one patient developed a retinal
detachment requiring further surgery. Patients who have vascularized
pigment epithelial detachment or subretinal fibrosis from AMD should
be excluded in our view from having this technique applied.
External Beam Irradiation for Macular Degeneration
External beam irradiation has been shown to be effective in the
treatment of hemangiomas (rare, benign tumors of the eye), and to
cause regression of abnormal blood vessels. The radiation induces
regression and/or promotes inactivation of the subretinal neovasculature.
Regression of the abnormal vasculature would result in reabsorption
of fluid and blood. Pilot experience with neovascularization from
macular degeneration suggests that low-dose radiotherapy (up to
2500 rads) offers a method to treat subretinal neovascularization
without destroying the overlying retina.
We have treated a number of patients with this type of irradiation.
These patients were either not eligible or were poor candidates
for laser photocoagulation, primarily because of the subfoveal location
of the CVM associated with pigment epithelial detachment, with or
without some subretinal fibrosis as defined by Digital Angiography,
and/or ICG.
Initial visual acuities ranged from 1/400 to 5/200. With a mean
follow-up of 8 months (3-18 months), we found 63% of the patients
were within two lines of their pretreatment visual acuity. Digital
angiographic imaging showed there was stabilization of subfoveal
neovascular membranes in 65%. New neovascular membranes have been
noted in five patients.
We believe that these results in this type of patient with poorly
defined choroidal neovascular membranes, with pigment epithelial
detachments, with or without an element of subretinal fibrosis can
affect active subretinal neovascularization. The technique does
buy time, but it is unlikely to prevent new neovascular events produced
by this chronic disease. Further investigation is warranted.
Our observations in this group of patients support the conclusion
that many patients will have improved or stable vision after treatment
with low-dose irradiation for age-related wet-type macular degeneration.
Gene Transfer
Biochemical mediators are being developed in major research and
development programs. This important class of therapeutic agents
are due to the advances in genetic engineering and biotechnology.
Delivery of genes to target sites is accomplished directly by putting
vector agents carrying the therapeutic genes to a target tissue.
This is accomplished by removing cells from the patient and placing
the desired gene into these cells which may then be placed back
into the patient. These therapeutic genes would be theoretically
used to cause a variety of effects including killing abnormal cells,
such as endothelial cells, which are causing the loss of vision
or to cause proliferation of cells to replace damaged cells which
normally do not proliferate, i.e., photoreceptor cells within the
retina.
The main challenge of this gene transfer approach is perfection
of the method for delivering the therapeutic gene to the patient's
target tissue. These vectors must provide a safe and efficient gene
delivery vehicle. The development of viral "smart vectors"
would carry the therapeutic gene to the specific tissue and cell
type. At present, it is possible to modify a virus and substitute
the desired therapeautic gene instead of an undesirable gene for
viral replication. The genetically altered virus could then transfer
the desired therapeutic genes to target tissues for the destruction
of abnormal cells or the production of new cells. The biggest challenge
at present is developing and altering these viruses so their ability
to deposit their genes into the target cells is controlled. In the
future, researchers will be able to choose one or a variety of gene
delivery systems for target tissues. This avenue of research offers
the most promise for the long term treatment of conditions, such
as AMD.
New Drug Treatments
AG 3340: Agouron Pharmaceuticals. A matrix metallaproteinases
inhibitor. This compound will enter phase III clinical trials. We
will be testing this compound in the national clinical trial.
anti-VEGF rhuFab: Genentech Pharmaceuticals. An inhibitor
of vascular endothelial growth factor (VEGF). This is in phase I
clinical trials.
anti-VEGF aptamer: Gilead/Nexstar Pharmaceuticals. Phase
1 clincial trials.
Anecortave acetate. Alcon Pharmaceuticals. This drug works
by preventing further angiogenesis (new blood vessel formation).
Phase I clinical trials.
LY3353l. Eli Lilly Pharmaceuticals. This compound is a
protein kinase L-Beta isoform inhibitor.
Click Here to find out about
our New England Retina Research and Education Foundation
Click Here to link to The Foundation
Fighting Blindness
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