by K. Bailey Freund, MD
(from
Volume 7, Issue 2, 1999)
When patients with pseudoxanthoma elasticum (PXE) develop
significant visual loss, it is usually due to one of two
processes. The first is a gradual, insidious process in
which degenerative changes beneath the central neurosensory
retina (macula) slowly damage this tissue. These “dry”
changes were discussed by Lawrence A. Yannuzzi, M.D., in our
previously article. This article will focus on the second
type of visual loss from choroidal neovascularization (CNV).
CNV is the growth of abnormal new blood vessels beneath the
retina. These abnormal vessels may leak fluid and/or blood
which distorts the retinal architecture and can eventually
lead to permanent scarring and visual loss. The new blood
vessels arise from a vascular layer beneath the retina known
as the choroid (hence the term “choroidal neovascularization”).
CNV also occurs in other macular diseases such as
age-related macular degeneration (AMD) and myopic macular
degeneration. When it occurs in AMD it is referred to as
the “wet” form of this disease.
The biologic mechanisms that are responsible for creating
CNV are currently being studied extensively. We know that
the macular diseases that develop this complication are all
characterized by degenerative changes in the tissue layers
which separate the neurosensory retina from the choroidal
blood vessels. These layers are known as the retinal
pigment epithelium (RPE) and Bruch’s membrane. In PXE
specifically, breaks in Bruch’s membrane produce secondary
changes of the overlying RPE. These changes are known as
angioid streaks. It is through these defects that CNV tends
to grow. The eye findings of PXE and their cause are
discussed in our previous article.
When choroidal neovascularization begins, often the first
symptom is distortion of straight lines (metamorphopsia).
It is important that patients who are predisposed to
choroidal neovascularization monitor their vision with an
Amsler grid to detect these early symptoms. (See Amsler
Grid pull-out section in the center of this newsletter.)
The treatment of choroidal neovascularization is an area of
intensive research. It is likely that these efforts will
result in continued improvements in our ability to manage
this disease in coming years.
Laser Treatment
To date, the
only treatment proven to be of benefit in some patients with
CNV is laser photocoagulation. The laser treatment
coagulates the vessels and stops them from spreading. The
treatment studies were performed primarily in patients with
CNV secondary to age-related macular degeneration. Thus,
the effectiveness of laser photocoagulation specifically for
CNV secondary to PXE has not been tested in large clinical
trials. However, clinically, many retina specialists feel
that laser is helpful in select cases. Unfortunately, only
a minority of patients with CNV are good candidates for
laser treatment. Eligibility depends on the size and
location of the CNV. In order to treat, one must be able to
identify the borders of the CNV through examination and
angiography. Even if the CNV can be localized, the area of
involvement may be too extensive to treat. After a complete
eye exam, an ophthalmologist can determine if laser
treatment might be beneficial. Your doctor will discuss
with you the benefits and risks of laser treatment for your
particular case.
The laser used for this surgery is a highly concentrated
energy source that emits a tiny spot of colored light. The
laser light passes through the transparent tissues of the
retina and is absorbed by the CNV and retinal pigment
epithelium (RPE) beneath the retina where it is converted
into heat. This heat burns the CNV and some of the
surrounding retinal tissues causing a small scar to form.
Your ophthalmologist will aim the laser directly at the CNV
beneath your retina. Usually, a lens is placed on the
treated eye to magnify the retina and stabilize the eye
being treated. Only minimal discomfort is felt as small
pulses of laser light are directed at the CNV. The
procedure is usually done on an outpatient basis with local
anesthesia (eye drops) and can be completed in a matter of
minutes.
If the CNV is successfully destroyed, it will no longer grow
or leak fluids into the retina. After treatment, the burned
area forms a permanent scar that will cause a blind spot in
your vision. It is important to realize that laser
treatment only sometimes improves vision, and can in some
cases make it worse. This is particularly true if the
location of the vessels means that it is necessary to treat
the central macula (fovea). In most cases, the scar
produced by the laser will be smaller than the scar that
would have resulted if the CNV had continued to grow beneath
the retina. Despite the fact that vision may be somewhat
worse after laser treatment, the rate of severe visual loss
is usually decreased over the long term when treatment is
successful.
Even if successful, laser treatment treats the CNV but not
the underlying disease process. It is not uncommon for CNV
to come back in the future. This high recurrence rate
accounts for a large portion of treatment failures.
Follow-up angiography is often necessary to watch for new
CNV. If new CNV is found, your ophthalmologist may
recommend additional laser treatment to preserve your
remaining vision.
Since
existing treatment options are appropriate for only a small
number of people with CNV, other methods of treatment are
being developed and tested. A wide variety of therapies are
being considered. I will briefly discuss some of these
experimental treatments.
Photodynamic Therapy
A promising
new treatment being studied for CNV is photodynamic therapy
(PDT). PDT involves a weak laser used in conjunction with a
special light-sensitive dye. In a procedure similar to
angiography, the special dye is injected into a vein in the
arm and allowed to circulate throughout the body. When the
dye circulates through the blood vessels of the eye, it
becomes concentrated in the areas of choroidal
neovascularization (CNV). Then, laser energy is applied to
the area of CNV. Sufficient heat to coagulate tissue is
generated only in areas where the dye has collected. In
this way, only the CNV (where the dye is concentrated) is
destroyed. The overlying retina is not damaged. If the
neovascularization recurs after photodynamic therapy, it can
be treated again with the same process. This treatment is
currently being tested and evaluated in a number of
clinics. Initial results appear very encouraging. Many
retina specialists believe that PDT will significantly
change the way CNV is treated in the future.
Low Dose Radiation Therapy
Radiation
therapy for CNV has received considerable attention in the
media. This treatment is currently under investigation in a
number of research centers. Since growing blood vessels are
very sensitive to radiation, it has been suggested that low
doses of radiation may stop or slow CNV. The studies
conducted so far have not yielded consistent results:
several small studies have demonstrated some beneficial
effects of radiation while other trials have shown no
benefit. Further study will be necessary to determine what
role (if any) radiation may play in the treatment of CNV in
the future.
Submacular Surgery
Submacular surgery attempts to remove CNV and/or blood from
beneath the retina. This technique requires that an
operative procedure known as vitrectomy be performed. In a
vitrectomy, the vitreous gel is surgically removed from the
eye and replaced with a saline solution. This is
accomplished using tiny instruments under an operating
microscope. Following the removal of the gel, a small
incision is made in the retina to gain access to the
subretinal space. Using fine microsurgical instruments, the
surgeon pulls the neovascular vessels out from under the
retina. He or she may also remove subretinal blood.
Although considerable advances have been made in technique
and instrumentation, results so far for the treatment of
degenerative macular diseases have been somewhat
disappointing. This appears to be largely due to the
limited capacity of the retinal tissues to heal and a high
rate of recurrence post-operatively. The effectiveness of
this technique is currently being evaluated in a large
clinical trial involving many centers.
Retinal Pigment Epithelial Transplantation
Retinal pigment epithelia (RPE) transplantation attempts to
replace diseased RPE with healthy RPE cells. It is hoped
that by re-establishing a normal RPE layer, degeneration of
the overlying retina can be prevented and perhaps partially
reversed. The procedure is similar to that of submacular
surgery. First, a vitrectomy is performed to remove the
vitreous gel from the eye. Then, a small incision is made
in the retina to gain access to the sub-retinal space. At
this point, healthy RPE cells are injected under the
retina. As time passes and the retina heals, it is hoped
that these transplanted RPE cells will arrange themselves
properly to replace the absent or diseased RPE. This
technique is being investigated in animal and human
studies. Rejection of transplanted tissue represents a
major obstacle to the success of this technique.
Macular Translocation
Macular translocation is another experimental surgical
procedure. The idea behind macular translocation is to move
the center of the macula when it is overlying sick
sub-retinal tissues such as CNV or diseased RPE. If the
central macula can be surgically moved to an area of healthy
tissue, it might be possible to prevent the damage that
would have otherwise occurred. With the macula moved away
from the CNV, the vessels can be treated more safely with
laser.
Several techniques have been tried to translocate the
central macula. All involve a vitrectomy procedure as the
initial step. Part of the retina is then detached from the
underlying tissues, cut and then rotated into a new
position. The rotated retina is reattached to an adjacent
area of healthier sub-retinal tissue. In some procedures,
the retinal rotations is combined with a foreshortening of
the wall of the eye. Surgically foreshortening the eye wall
limits the amount the retina has to be rotated, thereby
simplifying the procedure and possibly reducing potential
complication. While promising, these techniques are still
in the early stages of research.
Anti-angiogenic Drugs
We still do
not know the precise biochemical and physiological processes
that lead to CNV in some eyes with PXE. It has been
hypothesized that there are chemical stimulants called
angiogenic factors which are produced by sick and dying
tissues in the retina and that these substances stimulate
the onset of CNV. Angiogenesis is an area of active
research. It is hoped that through further understanding of
the underlying physiology, better drugs can be developed
which would inhibit choroidal neovascularization. In fact,
there are already several such drugs undergoing clinical
trials. However, their benefit has not yet been proven.
Conclusion
Although CNV
remains a difficult clinical challenge, converging lines of
research are progressing rapidly towards better treatments.
Through a better understanding of the biochemical causes of
CNV, novel approaches such as those described above are
being developed and pursued. We hope and expect that one or
more of these therapies will be successful in greatly
reducing the impact that CNV has on the patients who develop
it from PXE/angioid streaks and other maculopathies.
Note: This
article comes from the LuEsther T. Mertz Retinal Research
Center. Dr. K. Bailey Freund is a member of Vitreous
Retinal Macula Consultants of New York. He is an instructor
in Clinical Ophthalmology at the Edward S. Harkness Eye
Institute; Assistant Attending Surgeon at New York
Presbyterian Hospital; Assistant Attending Surgeon at
Manhattan Eye, Ear, & Throat Hospital. Dr. Freund is
currently collaborating with the Department of Dermatology
at the Mt. Sinai School of Medicine studying how an oral
medication which lowers serum phosphate levels affects the
skin and eye changes of PXE. For information on this study
and other research contact Katherine Burke at the LuEsther
T. Mertz Retinal Research Center (212) 605-3777.
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