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Retinal Thickness May Augur Brain Atrophy in MS


BALTIMORE -- A noninvasive scan of the retinal nerve fiber layer may offer clues to the progression of multiple sclerosis, investigators here reported.

BALTIMORE, Oct. 15 -- A noninvasive scan of the retinal nerve fiber layer may offer clues to the progression of multiple sclerosis, investigators here reported.

In 40 patients with MS and 15 healthy controls, there was a strong, albeit imperfect correlation between minimum retinal nerve fiber layer thickness and the degree of whole brain atrophy as seen on MRI, according to Peter A. Calabresi, M.D., of Johns Hopkins, and colleagues.

When they looked at a subset of patients with relapsing-remitting MS, the researchers found that the correlation between the optical coherence tomography (OCT) retinal scans and brain parenchymal fraction on MRI was even stronger, the authors reported in the Oct. 16 issue of Neurology.

"This is an encouraging result," said Dr. Calabresi, M.D. "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."

Similar in concept to holography, OCT uses interference patterns of light across a broad spectrum to measure noninvasively the thickness of the retinal nerve fiber layer. Thinning of the retinal nerve fiber layer occurs with various ocular disorders, including macular degeneration, glaucoma, and retinitis pigmentosa.

In addition to its potential as a disease monitoring tool, optical coherence tomography may also provide valuable insights into MS pathogenesis, suggested Stephen G. Waxman, M.D., Ph.D., and Joel A. Black, Ph.D., from Yale University School of Medicine in New Haven, Conn., in an accompanying editorial.

"Serial evaluations of the retinal nerve fiber layer, using OCT, may prove to be useful for clinical studies on the natural history of MS and also on the response to putative treatments," they wrote. "In addition, however, OCT may permit us to capitalize upon the unique structure of retinal ganglion neurons and their axons so that we can learn more about fundamental mechanisms of neuronal injury in MS."

Dr. Calabresi and colleagues enrolled 40 patients with MS and 15 controls into their study. All patients and controls underwent OCT and cranial MRI scans. The authors estimated brain parenchymal fraction, a measure of whole brain atrophy and partial brain volumes. They created multiple linear regression models to examine the association between OCT and MRI measures of atrophy.

The investigators found that a combination of minimum retinal nerve fiber layer thickness and age of the study participant predicted 21% of the variance in brain parenchymal fraction among all MS patients (P=0.005), but not among controls.

In addition, when they looked at the 20 MS patients who had relapsing-remitting disease, they found that retinal nerve fiber layer and age predicted 43% of the variance in brain parenchymal fraction (P=0.003).

Among all patients, the partial correlation coefficient for brain parenchymal fraction and retinal nerve fiber layer thickness controlled for age was 0.46 (P=0.003).

For the patients with relapsing-remitting disease, the age-corrected correlation coefficient was 0.69 (P= 0.001).

However, there was no association between OCT and MRI findings for the 15 patients with secondary-progressive MS; the remaining five patients had primary progressive MS, but this sample size was too small to detect associations, the authors noted.

"These associations are driven by cerebrospinal fluid volume but not by gray or white matter volume. There is no significant association of these variables among controls," the authors wrote.

They concluded that using OCT to quantify axonal thickness in the retinal nerve fiber layer can provide concurrent information about brain abnormalities as seen on MRI, and called for longitudinal studies to see whether the OCT/MRI correlation could be used to monitor outcomes in clinical trials of neuroprotective agents.

In their editorial, Dr. Waxman and Dr. Black noted that "OCT may contribute to a 'mapping' of pathologic events along the various domains of retinal ganglion neurons. To the degree that these cells are a good model, they may help us to understand neurons as disease targets in MS."

The authors acknowledged that the lack of association in the control group may be a function of the small sample size and relative youth of the controls, especially given that retinal nerve fiber layer thinning and brain volume loss can occur in healthy people later in life and may be associated with one another. They suggested longitudinal studies to further explore that issue.

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