and Medicine for Seniors
New Discovery Detects Most Damaging
Age-Related Macular Degeneration
Retinal-scan analysis can predict which AMD
patients may go blind
Nov. 5, 2014 - A new way to forecast which patients
with age-related macular degeneration are likely to suffer from the most
debilitating form of the disease has been found by Stanford University
School of Medicine scientists. AMD is the leading cause of blindness and
central vision loss among senior citizens older than 65.
The new discovery predicts, on a personalized
basis, which patients' AMD would, if untreated, probably make them
blind, and roughly when this would occur. Simply by crunching imaging
data that is already commonly collected in eye doctors' offices,
ophthalmologists could make smarter decisions about when to schedule an
individual patient's next office visit in order to optimize the chances
of detecting AMD progression before it causes blindness.
An estimated 10-15 million people in the United
States suffer from the disease, in which the macula — the key area of
the retina responsible for vision — shows signs of degeneration. During
normal aging, yellowish deposits called drusen form in the retina, which
is the light-sensitive layer of tissue at the back of the eye. As drusen
increase in size and number, they eventually begin to damage the
light-sensitive cells of the macula. This stage of the disease, called
"dry" AMD, can mean blurry central vision and impaired day-to-day
While about four of every five people with AMD have
the dry form of the disease, it's the so-called "wet" form that most
concerns ophthalmologists, because it accounts for 80-90 percent of all
legal blindness associated with the disease. In wet AMD, abnormal blood
vessels accumulate underneath the macula and leak blood and fluid. When
that happens, irreversible damage to the macula can quickly ensue if not
But until now, there has been no effective way to
tell which individuals with AMD are likely to progress to the wet stage.
Current treatments are costly and invasive — they typically involve
injections of medicines directly into the eyeball — making the notion of
treating people with early or intermediate stages of AMD a non-starter.
Doctors and patients have to hope the next office visit will be early
enough to catch wet AMD at its onset, before it takes too great a toll.
Predicting Progression to 'Wet' AMD
In a study published in the November issue of
Investigative Ophthalmology & Visual Science, the researchers derived a
formula that they say predicts, with high accuracy, whether a patient
with mild or intermediate AMD will progress to the wet stage. The
formula distinguishes likely from unlikely progressors by analyzing
patient data that's routinely collected by ophthalmologists and
optometrists when they perform retinal scans with an imaging technique
called spectral domain optical coherence tomography.
This imaging technique is analogous to ultrasound:
The macula is scanned with a beam of focused laser light, and the amount
of reflected light coming back at each point is measured and recorded.
The resulting stream of data is computationally converted into an
extremely high-resolution, three-dimensional image.
"Right now, a patient who goes into the
ophthalmologist's office typically gets an SD-OCT scan anyway," said the
study's senior author, Daniel Rubin, MD, assistant professor of
radiology and of biomedical informatics. "Our technique involves no new
procedures in the doctor's office — patients get the same care they've
been getting anyway. We've simply added on a computerized
image-processing step that analyzes not only that scan but any previous
ones available from that same patient's earlier visits."
Generating a Risk Score
From this computerized analysis, the investigators
are able to generate a risk score: a number that predicts a patient's
likelihood of progressing to the wet stage within one year, three years
or five years. The likelihood of progression within one year is most
relevant, because it translates into a concrete recommendation: how soon
to schedule the patient's next office visit.
Until now, attempts to predict AMD progression have
relied on eye doctors examining color photographs of the retina taken in
their offices. There is no way to translate that information into risk
scores. The high-resolution imaging technique, Rubin said, provides much
richer detail. "You can almost see individual cells," he said.
"Plus," he added, "it is far more amenable to
digital analysis. Previously proposed predictive models have shown some
accuracy over long periods of time, but none has been adequately
accurate over the shorter, one-year time frame that's relevant to making
decisions about office-visit frequency."
In the study, the Stanford team analyzed data from
2,146 scans of 330 eyes in 244 patients seen at Stanford Health Care
over a five-year period. They found that certain key features in the
images, such as the area and height of drusen, the amount of
reflectivity at the macular surface and the degree of change in these
features over time, could be weighted to generate a patient's risk
Patients were followed for as long as four years, and predictions
of the model were compared with actual instances of progression to wet
AMD. The model accurately predicted every occurrence of progression to
the wet stage within a year. About 40 percent of the time when the model
did predict progression to wet AMD within a year, the prediction was not
"No test gets it right 100 percent of the time,"
Rubin said. "You can tweak the model to trade off the risk of telling
someone they will progress when they actually won't against the risk of
telling them they won't progress when they actually will. With AMD you
really don't want any false negatives, so you tune the model
accordingly. The downside is that some patients will wind up being told
to come in sooner than, in fact, they probably need to. But that's
nothing compared with the downside of a patient at high risk for
progression's not coming in soon enough."
Larger Studies Needed
Rubin emphasized that this proof-of-principle study
needs to be followed up by a larger study, ideally using data gathered
from patients seen at other institutions. He and his associates have now
embarked on such a study.
>> For more information about AMD, visit
>> The study's lead author is Luis de Sisternes, PhD,
a postdoctoral scholar in radiology. Other Stanford co-authors are
Robert Tibshirani, PhD, professor of health research and policy and of
statistics; Theodore Leng, MD, clinical assistant professor of
ophthalmology; and former postdoctoral scholar Noah Simon, PhD, now at
the University of Washington.
>> The work was supported by grants from Stanford
Bio-X and Spectrum-Stanford Predictives and Diagnostics Accelerator.
Information about Stanford's Department of
Radiology, which also supported this work, is available at
>> The Stanford University School of Medicine reports
it consistently ranks among the nation's top medical schools,
integrating research, medical education, patient care and community
service. For more news about the school, please visit
http://med.stanford.edu/school.html. The medical school is
part of Stanford Medicine, which includes Stanford Health Care and
Lucile Packard Children's Hospital Stanford. For information about all
three, please visit