In a study of nearly 650 people with the eye disease
age-related macular degeneration (AMD), half still
had vision 20/40 or better, typically good enough to
drive or to read standard print, after five years of
treatment with anti-VEGF drugs that are injected
into the eye.
The authors of the study, funded by the National Eye
Institute (NEI) at the National Institutes of
Health, say those outcomes would have been
unimaginable about 10 years ago, prior to the drugs'
availability.
The results were published in the journal
Ophthalmology and presented May 2nd at the annual
meeting of the Association for Research in Vision
and Ophthalmology (ARVO) in Seattle.
“This is the most comprehensive study of anti-VEGF
therapy for AMD to date,” said NEI Director Paul A.
Sieving, M.D., Ph.D. “It points to the importance of
long-term follow-up in studies evaluating disease
treatments.”
AMD is the leading cause of vision loss among older
Americans. It causes damage to the central part of
the retina, the light-sensitive tissue at the back
of the eye. AMD often has very few symptoms in its
early stages; but in later stages, it causes loss of
the central, straight-ahead vision needed for
activities like reading and driving.
There are two types of late AMD — geographic
atrophy, and the more common neovascular AMD, also
known as wet AMD.
In neovascular AMD, fragile blood vessels grow under
the retina and leak fluid. This usually starts in
one eye, and is stimulated by a protein called VEGF.
Just 10 years ago, people diagnosed with neovascular
AMD were almost certain to develop severe vision
loss in their affected eye and likely to lose vision
in their other eye, too.
The new study looked at people with AMD who had
regular treatment with drugs designed to block VEGF.
After five years, 50 percent of them had 20/40
vision or better, 20 percent had 20/200 vision or
worse, and the rest were in-between.
Ten years ago, the best available treatment for AMD
was photodynamic therapy — in which an intravenous
drug (injected into a vein) and laser are used to
seal off leaking blood vessels.
Past studies have found that just one year after
diagnosis, less than 15 percent of patients given
this therapy alone retain 20/40 vision, and up to 40
percent decline to 20/200 vision. Without any
treatment, less than 10 percent of patients retain
20/40 vision at one year, and up to 75 percent of
untreated patients decline to 20/200 vision.
In the U.S., state drivers’ licenses generally
require 20/40 vision in at least one eye. A
best-corrected vision of 20/200 in both eyes is
considered legally blind for the purpose of federal
disability benefits.
The Comparison of AMD Treatments Trials (CATT) began
in 2008 and was designed to compare the anti-VEGF
drugs Avastin and Lucentis.
VEGF is important in the growth and development of
new blood vessels in normal and cancerous tissues.
Avastin (bevacizumab) was approved by the Food and
Drug Administration in 2004 for the treatment of
metastatic colon cancer.
Other drugs were later developed specifically to
target blood vessels in the retina, with Lucentis (ranibizumab)
coming to the market in 2006 and Eylea (aflibercept)
in 2011.
For treating AMD, the drugs are injected into the
eye. Before Lucentis was available, many
ophthalmologists began treating the disease with
Avastin, which appeared to have similar benefits, at
least in the short-term. The difference in the cost
of the drugs also made Avastin appealing; the
approximate per-dose price was $50 for Avastin and
$2000 for Lucentis.
In the trial, more than 1200 participants with
neovascular AMD were randomly assigned to receive
either Lucentis or Avastin for two years, through
monthly or as-needed injections. During that time,
the two drugs were equally effective at preserving
visual acuity. These results were later confirmed in
five multicenter clinical trials around the world.
The current study followed up with CATT participants
between March 2014 and 2015, an average of 5.5 years
after enrollment in the trial.
After two years on their assigned drug, participants
were free to work with their eye care providers to
choose their own course of therapy. During that
3.5-year period, more than half received at least
one treatment with a drug or therapy other than the
drug assigned to them. The investigators obtained
visual acuity measurements for 647 of 914
participants who were still living.
In addition to the overall effects of anti-VEGF
therapy at five years, the investigators compared
the outcomes of participants who received Avastin or
Lucentis during the trial.
“Some experts had speculated that two years of
treatment with ranibizumab might have long-term
benefits superior to bevacizumab. However, at five
years, there were no differences in visual acuity
between the two drugs,” said Daniel F. Martin, M.D.,
chair of the Cleveland Clinic Cole Eye Institute and
CATT study chair.
The study also found that after five years,
participants assigned to Lucentis during the trial
had a higher rate of strokes and heart attacks (7.6
percent) than those assigned to Avastin (4.5
percent).
Since most participants received treatments other
than their assigned drug after the two year-trial,
the investigators are cautious about attributing
this difference to the study drugs.
Finally, the study provides information on the
general course of AMD with treatment.
It was already known that many people with
neovascular AMD eventually develop geographic
atrophy, which has no treatment.
In the trial, participants were more likely to
develop geographic atrophy when they received
monthly, rather than as-needed injections of Avastin
or Lucentis.
After the trial, almost all participants stopped
monthly injections in favor of as-needed treatment,
with an average of 4-5 injections per year.
By five years, the rate of geographic atrophy
increased from 20 percent of participants at two
years to 41 percent at five years.
The fraction of participants with geographic atrophy
was similar between the Avastin and Lucentis groups.
“Although anti-VEGF treatment has greatly improved
the prognosis for patients overall, we still need to
find ways to avoid poor vision in these patients and
to decrease the burden of ongoing treatment,” said
Maureen G. Maguire, Ph.D., the study’s principal
investigator and a professor of ophthalmology in the
Perelman School of Medicine at the University of
Pennsylvania in Philadelphia.
For more information
CATT Research Group.
Five-year outcomes with anti-vascular endothelial
growth factor treatment for neovascular age-related
macular degeneration: The Comparison of Age-Related
Macular Degeneration Treatments Trials.
Ophthalmology. May 2, 2016.
DOI: 10.1016/j.ophtha.2016.03.045
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