A five-minute eye exam might prove to be an inexpensive and
effective way to gauge and track
the debilitating neurological disease multiple sclerosis,
potentially complementing costly magnetic
resonance imaging to detect brain shrinkage, a characteristic of
the disease's progression.
A Johns Hopkins-based study of a group of 40 multiple
sclerosis patients used a process called
optical coherence tomography to scan the layers of nerve fibers
of the retina in the back of the eye,
which become the optic nerve. The OCT process, which uses a
desktop machine similar to a slit-lamp, is
simple and painless. The retinal nerve fiber layer is the one
part of the brain where nerve cells are not
covered with the fat and protein sheathing called myelin, making
this assessment specific for nerve
damage as opposed to brain MRI changes, which reflect an array of
different types of tissue
processes in the brain.
Results of the scans were calibrated using accepted norms
for retinal fiber thickness and then
compared to an MRI of each patient's brains, also calibrated
using accepted norms. Experimenters
found a correlation coefficient of 0.46, after accounting for age
differences. Correlation coefficients
represent how closely two variables are related — in this
case MRI of the brain and OCT scans.
Correlation coefficients range from -1 (a perfect opposing
correlation) through 0 (no correlation) to +1
(a perfect positive correlation). In a subset of patients with
relapsing remitting MS, the most common
form of the disease, the correlation coefficient jumped to 0.69,
suggesting an even stronger
association between the retinal measurement and brain atrophy.
"This is an encouraging result," said Johns Hopkins neurologist Peter
Calabresi, lead author of
the study, which appears in the October issue of
Neurology. "MRI is an imperfect tool that measures
the result of many types of tissue loss rather than specifically
nerve damage itself. With OCT we can
see exactly how healthy these nerves are, potentially in advance
of other symptoms."
In addition, Calabresi said, OCT scans take roughly
one-tenth as long and cost one-tenth as
much as the MRI, which means they are faster and cheaper to use
in studies that track the
effectiveness of new treatments for MS.
Approximately 400,000 people in the United States have MS,
which is marked by an abnormal
immune system that attacks and kills a person's own brain cells.
As these neurons die, the volume of
the brain decreases. MRI of the brain, which can measure total
volume, has long been the primary tool
used to monitor MS. But MRI, aside from being expensive and
uncomfortable, is often misleading since
brain inflammation — also a symptom of the disease —
can skew brain volume readings. Also, the brain
begins shrinking relatively late in the progression of the
disease, and MRI isn't as good at detecting
the disease in its early stages, when treatments are most
effective. OCT scans look directly at the
thickness, and therefore health, of the optic nerve, which is
affected early on in the disease, often
before the patient suffers permanent brain damage.
Calabresi added that many of the disabilities suffered by MS
patients — numbness, tingling,
visual impairment, fatigue, weakness and bladder function
disturbance — are the result of nerve cell
degeneration, so a test that specifically measures nerve cell
health is potentially the clearest picture
of the status of the disease.
He cautions that optic nerve damage can point to a number of
diseases and is not a unique
diagnostic tool for MS. However, he said, it certainly sends up a
flag suggesting that MS might be
present. And since optic nerve damage is one of the first
recognizable symptoms of MS, doctors
potentially have a chance to identify the disease before the
patient suffers the physical limitations
generally associated with its advanced stages.
"Treatments for MS cannot reverse the damage, but they can
arrest it, so the earlier we get
someone on medication, the quicker we can stop the disease from
causing more harm," Calabresi said.
Also, this tool may be useful as an outcome measure in MS
clinical trials to assess the efficacy of
neuroprotective drugs.
In the study, researchers recruited 40 patients from the
Johns Hopkins MS clinic. Twenty had
relapsing remitting MS, 15 had secondary progressive MS, and five
had primary progressive MS. As a
comparison group, researchers recruited 15 healthy control
patients free from ophthalmological or
neurological disease.
Calabresi said his next step will be to look at changes in
the fiber layer thickness in 100
patients over a period of three years.
Additional researchers who worked on this study include
Eliza Gordon-Lipkin and Daniel S.
Reich, both of the Johns Hopkins School of Medicine; Seth A.
Smith and BettyAnn Chodkowski, of the
Kennedy Krieger Institute; Mathew Pulicken, of the Johns Hopkins
Bloomberg School of Public Health;
Elliot M Frohman, of the University of Texas, Dallas; Gary
Cutter, of the University of Alabama; and
Laura Balcer, of the University of Pennsylvania.
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