Eye changes may signal frontotemporal lobe degeneration

September 08, 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 patients with FTD showed thinning of the outer retina--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.
-end-
Other Penn co-authors include David J. Irwin, Delu Song, Ebenezer Daniel, Jennifer D. Leveque, Aaishah R. Raquib, Wei Pan, Gui-Shuang Ying, Tomas S. Aleman, and Joshua L. Dunaief, all of Penn Medicine at the time of the study.

Funding for the study was provided by the National Institutes of Health (AG017586, NS053488, AG052943, 2-P30-EY01583-26, and K23NS088341).

Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $6.7 billion enterprise.

The Perelman School of Medicine has been ranked among the top five medical schools in the United States for the past 20 years, according to U.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $392 million awarded in the 2016 fiscal year.

The University of Pennsylvania Health System's patient care facilities include: The Hospital of the University of Pennsylvania and Penn Presbyterian Medical Center -- which are recognized as one of the nation's top "Honor Roll" hospitals by U.S. News & World Report -- Chester County Hospital; Lancaster General Health; Penn Wissahickon Hospice; and Pennsylvania Hospital -- the nation's first hospital, founded in 1751. Additional affiliated inpatient care facilities and services throughout the Philadelphia region include Good Shepherd Penn Partners, a partnership between Good Shepherd Rehabilitation Network and Penn Medicine.

Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2016, Penn Medicine provided $393 million to benefit our community.

University of Pennsylvania School of Medicine

Related Brain Articles from Brightsurf:

Glioblastoma nanomedicine crosses into brain in mice, eradicates recurring brain cancer
A new synthetic protein nanoparticle capable of slipping past the nearly impermeable blood-brain barrier in mice could deliver cancer-killing drugs directly to malignant brain tumors, new research from the University of Michigan shows.

Children with asymptomatic brain bleeds as newborns show normal brain development at age 2
A study by UNC researchers finds that neurodevelopmental scores and gray matter volumes at age two years did not differ between children who had MRI-confirmed asymptomatic subdural hemorrhages when they were neonates, compared to children with no history of subdural hemorrhage.

New model of human brain 'conversations' could inform research on brain disease, cognition
A team of Indiana University neuroscientists has built a new model of human brain networks that sheds light on how the brain functions.

Human brain size gene triggers bigger brain in monkeys
Dresden and Japanese researchers show that a human-specific gene causes a larger neocortex in the common marmoset, a non-human primate.

Unique insight into development of the human brain: Model of the early embryonic brain
Stem cell researchers from the University of Copenhagen have designed a model of an early embryonic brain.

An optical brain-to-brain interface supports information exchange for locomotion control
Chinese researchers established an optical BtBI that supports rapid information transmission for precise locomotion control, thus providing a proof-of-principle demonstration of fast BtBI for real-time behavioral control.

Transplanting human nerve cells into a mouse brain reveals how they wire into brain circuits
A team of researchers led by Pierre Vanderhaeghen and Vincent Bonin (VIB-KU Leuven, Université libre de Bruxelles and NERF) showed how human nerve cells can develop at their own pace, and form highly precise connections with the surrounding mouse brain cells.

Brain scans reveal how the human brain compensates when one hemisphere is removed
Researchers studying six adults who had one of their brain hemispheres removed during childhood to reduce epileptic seizures found that the remaining half of the brain formed unusually strong connections between different functional brain networks, which potentially help the body to function as if the brain were intact.

Alcohol byproduct contributes to brain chemistry changes in specific brain regions
Study of mouse models provides clear implications for new targets to treat alcohol use disorder and fetal alcohol syndrome.

Scientists predict the areas of the brain to stimulate transitions between different brain states
Using a computer model of the brain, Gustavo Deco, director of the Center for Brain and Cognition, and Josephine Cruzat, a member of his team, together with a group of international collaborators, have developed an innovative method published in Proceedings of the National Academy of Sciences on Sept.

Read More: Brain News and Brain Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.