Eye changes may signal frontotemporal lobe degeneration

September 8, 2017

Frontotemporal degeneration (FTD) is a progressive neurodegenerative condition that is present in tens of thousands of Americans, but is often difficult to diagnose accurately. Now in a study published this week online ahead of print in Neurology, researchers from the Perelman School of Medicine at the University of Pennsylvania have found evidence that a simple eye exam and retinal imaging test may help improve that accuracy.

Using an inexpensive, non-invasive, eye-imaging technique, the Penn Medicine scientists found that with FTD showed thinning of the outer —the layers with the photoreceptors through which we see—compared to control subjects.

The retina is potentially affected by neurodegenerative disorders because it is a projection of the brain. Prior studies have suggested that patients with Alzheimer's disease and ALS may also have thinning of the retina—although a different part of the retina. Thus, imaging the retina may help doctors confirm or rule out FTD.

"Our finding of outer retina thinning in this carefully designed study suggests that specific brain pathologies may be mirrored by specific retinal abnormalities, said study lead author Benjamin J. Kim, MD, assistant professor of Ophthalmology at Penn's Scheie Eye Institute.

Neurodegenerative diseases in general are challenging to diagnose, and often are confirmed only by direct examination of brain tissue at autopsy. Now that science appears to be on the brink of developing effective treatments for these diseases, the need for better diagnostic methods is becoming acute.

"As we enter an era of disease-modifying treatments for neurodegenerative disorders, it is essential for us to have tools that can identify the specific pathologies accumulating in the brain so that we can administer the appropriate treatments to patients who are likely to benefit," said study senior author Murray Grossman, MD, a professor of Neurology and director of the Penn FTD Center.

The study included 38 FTD patients enrolled consecutively as they visited the Penn FTD Center, and 44 control subjects who did not have any neurodegenerative disease. The FTD patients were carefully characterized with clinical exams, cerebrospinal fluid biomarkers to exclude Alzheimer's Disease, and genetic testing. The researchers then employed an eye-imaging technology called spectral-domain optical coherence tomography (SD-OCT), which uses a safe light beam to image tissue with micron-level resolution. SD-OCT imaging is inexpensive, non-invasive, and quick.

Measurements of the retinal layers of the subjects, after adjustments for age, gender, and ethnic background, showed that the outer retinas of the FTD patients were thinner than those in the control subjects. This relative thinning of outer retinas was caused by a thinning of two specific portions of the outer retina, the outer nuclear layer (ONL) and ellipsoid zone (EZ). The ONL of FTD patients was about 10% thinner than controls, and this ONL thinning was the primary source of the outer retina thinning.

The degree of retinal thinning among FTD patients also had a significant tendency to be worse when the patients' scores on a standard cognition test were lower.

Prior studies have found a loss of optic nerve fibers and associated thinning of the inner retina in a few other neurodegenerative disorders including Alzheimer's, ALS, and Lewy-body dementia. The new results suggest that FTD manifests in a different way in the structures of the retina, and that this difference, detectable with a retinal imaging test, might help doctors distinguish one disorder from another. FTD is among the most common causes of midlife dementia, and is often misdiagnosed as Alzheimer's—or vice versa.

FTD itself is not a single disorder but rather a grouping of distinct disorders. The results from the new study suggest that it may be possible to use SD-OCT imaging to distinguish among these FTD subtypes.

Some FTD subtypes involve the abnormal accumulation, in affected brain areas, of thread-like aggregates of a protein called tau. Other FTD subtypes feature abnormal aggregates of a protein called TDP-43. In the study, the Penn researchers used normal clinical criteria to group the FTD patients into probable-tau, probable-TDP-43, and unknown pathology categories. They observed that the outer retinal thinning seemed to occur chiefly in the probable-tau pathology group.

"Prior studies have suggested that tau is expressed in photoreceptor cells, and so we hypothesized that patients with tau brain pathology may have photoreceptor abnormalities," Kim said. "It was exciting to acquire data that appear to confirm our hypothesis."

The Penn researchers now plan larger, more conclusive studies to compare retinal measurements among patients who have different FTD subtypes as well as other neurodegenerative diseases.

Explore further: Zika, cobalamin C deficiency tied to similar retinal problems

Related Stories

Zika, cobalamin C deficiency tied to similar retinal problems

September 8, 2017
(HealthDay)—Retinal maldevelopment associated with congenital Zika syndrome (CZS) is similar to the maldevelopment seen with cobalamin C (cblC) deficiency, according to a study published online Sept. 7 in JAMA Opthalmology.

Zika virus can cause severe damage to retina in infants

November 10, 2016
In a study published online by JAMA Ophthalmology, Rubens Belfort Jr., M.D., Ph.D., of the Federal University of Sao Paulo, Brazil, and colleagues examined the affected retinal layers in infants with congenital Zika syndrome ...

Retinal thinning can be used as an early marker for frontotemporal dementia

August 25, 2014
Researchers at the Gladstone Institutes and University of California, San Francisco have shown that a loss of cells in the retina is one of the earliest signs of frontotemporal dementia (FTD) in people with a genetic risk ...

GARP2 accelerates retinal degeneration in a mouse model

February 15, 2017
In the retina of the eye, rod and cone cells turn light into electrical signals, the first step toward human vision. University of Alabama at Birmingham researchers are studying rod cell proteins GARP1 and GARP2 to learn ...

Eye scan could help track progress of multiple sclerosis

December 24, 2012
(HealthDay)—In-office eye scans that assess the thinning of the retina may also help doctors determine how fast multiple sclerosis (MS) is progressing in patients with the nervous system disease, a new study suggests.

Photoreceptor cell death leads to blindness in CLN5 form of Neuronal Ceroid Lipofuscinosis

May 16, 2017
Researchers from the University of Eastern Finland have discovered a likely cause for visual impairment and eventual loss of vision in the Finnish variant of Neuronal Ceroid Lipofuscinosis (NCL). Visual impairment associated ...

Recommended for you

Research redefines proteins' role in the development of spinal sensory cells

September 19, 2017
A recent study led by Samantha Butler at the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA has overturned a common belief about how a certain class of proteins in the spinal cord regulate ...

The brain at work: Spotting half-hidden objects

September 19, 2017
How does a driver's brain realize that a stop sign is behind a bush when only a red edge is showing? Or how can a monkey suspect that the yellow sliver in the leaves is a round piece of fruit?

Team discovers how to train damaging inflammatory cells to promote repair after stroke

September 19, 2017
White blood cells called neutrophils are like soldiers in your body that form in the bone marrow and at the first sign of microbial attack, head for the site of injury just as fast as they can to neutralize invading bacteria ...

Epileptic seizures show long-distance effects

September 19, 2017
The area in which an epileptic seizure starts in the brain, may be small but it reaches other parts of the brain at distances of over ten centimeters. That distant activity, in turn, influences the epileptic core, according ...

Study uncovers markers for severe form of multiple sclerosis

September 18, 2017
Scientists have uncovered two closely related cytokines—molecules involved in cell communication and movement—that may explain why some people develop progressive multiple sclerosis (MS), the most severe form of the disease. ...

Genetically altered mice bear some hallmarks of human bipolar behavior

September 18, 2017
Johns Hopkins researchers report they have genetically engineered mice that display many of the behavioral hallmarks of human bipolar disorder, and that the abnormal behaviors the rodents show can be reversed using well-established ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.