A simple eye test for multiple sclerosis

As you step outdoors into the bright sunshine, your pupils automatically contract. Scientists from the Australian Centre of Excellence in Vision Science (ACEVS) based at The Australian National University (ANU) are making use of how this ‘pupil reflex’ is connected to the brain as a potential new way of testing the severity of multiple sclerosis (MS).

Dr Eman Ali and her ACEVS colleagues have used an instrument they are developing to accurately measure the pupil responses of MS patients and have found that the pupils of MS sufferers respond appreciably slower. The finding opens the door to a simple and quick way of tracking the severity of MS over time: the slower the response, the worse the MS.

“Our instrument uses special patterns of flashing lights that the patient looks at for four minutes,” says Professor Ted Maddess, a vision scientist at ANU who is head of the ACEVS team.

“We use infrared cameras to measure light-induced changes in the diameters of both pupils, and with computer tracking we can measure the diameter to within a micrometre 30 times a second.

“We have just published the results of our study of 85 MS patients, and we find that in MS patients the pupil response is about 25 milliseconds slower than in our control group. Although the study is preliminary, we believe the test has good potential in individual patients because it can precisely measure the speed of their response to within a millisecond.

“So instead of an expensive MRI to track the condition, the new method gives an accurate readout after just a few minutes. That quick and easy test might, in the future, allow MS patients to be assessed on the spot and have their medication adjusted accordingly,” he says.

MS is a potentially devastating neurological condition affecting the myelin sheath of nerve fibres, leading to sensory disturbances and muscle weakness. Vision, speech, and walking are most often affected, and pain can occur. Puzzlingly, MS affects different people in different ways, but the condition inexorably gets worse with age and there is currently no cure. Some patients experience acute, inflammatory attacks while others don’t.

“MS is the most common neurological disability in adults, with about 12,000 sufferers in Australia,” says Professor Maddess. “Although it seems to be some sort of immune disorder, its cause is still obscure.

“There are many puzzling aspects to MS, and there are many theories,” he says. “But our main aim in this work was just to find a way of accurately monitoring the progression of the disease, a single measure that relates to the degree of disability. MRI is good for giving insight into the inflammation associated with episodic attacks, but it’s not so good at monitoring the chronic decline that’s always going on.

“If we can use our pupil measurements to monitor the decline, we might be in a better position to adjust medications, which often have unpleasant side-effects.”

The instrument to measure the pupil responses is the same one which has also been shown to be helpful in diagnosing vision loss in glaucoma, diabetes, and age-related macular degeneration. The device was developed by Professor Maddess together with Associate Professor Andrew James and other ACEVS team members. Under the name TrueField, it is being commercially developed by an Australian company, Seeing Machines, which plans to sell it as a multipurpose medical diagnostic instrument.

TrueField has already received American FDA clearance, and Professor Maddess is hopeful it might, after some more research, also find a role in monitoring MS. He believes it has good prospects of reducing the high treatment costs associated with the disease.

The paper by Dr Ali and colleagues, “Pupillary response to sparse multifocal stimuli in multiple sclerosis patients”, is available online in the Multiple Sclerosis Journal.

Can the Eyes Help Diagnose Alzheimer’s Disease?

An international team of researchers studying the link between vision loss and Alzheimer’s disease report that the loss of a particular layer of retinal cells not previously investigated may reveal the disease’s presence and provide a new way to track disease progression.

The researchers, from Georgetown University Medical Center (GUMC) and the University of Hong Kong, examined retinas from the eyes of mice genetically engineered to develop Alzheimer’s disease (AD). They presented their findings today at Neuroscience 2013, the annual meeting of the Society for Neuroscience.

“The retina is an extension of the brain so it makes sense to see if the same pathologic processes found in an Alzheimer’s brain are also found in the eye,” explains R. Scott Turner, MD, PhD, director of the Memory Disorders Program at GUMC and the only U.S. author on the study. “We know there’s an association between glaucoma and Alzheimer’s in that both are characterized by loss of neurons, but the mechanisms are not clear.” 

Turner says many researchers increasingly view glaucoma as a neurodegenerative disorder similar to AD.

Most of the research to date examining the relationship between glaucoma and Alzheimer’s focused on the retinal ganglion cell layer, which transmits visual information via the optic nerve into the brain. Before that transmission happens, though, the retinal ganglion cells receive information from another layer in the retina called the inner nuclear layer.

In their study, the researchers looked at the thickness of the retina, including the inner nuclear layer (not previously study in this setting) and the retinal ganglion cell layer.  They found a significant loss of thickness in both. The inner nuclear layer had a 37 percent loss of neurons and the retinal ganglion cell layer a 49 percent loss, compared with healthy, age-matched control mice.

In humans, the structure and thickness of the retina can be readily measured using optical coherence tomography.  Turner says this new tool is increasing finding applications in research and clinical care. 

“This study suggests another path forward in understanding the disease process and could lead to new ways to diagnose or predict Alzheimer’s that could be as simple as looking into the eyes,” Turner says. “Parallel disease mechanisms suggest that new treatments developed for Alzheimer’s may also be useful for glaucoma.”

Vision restored with total darkness

Restoring vision might sometimes be as simple as turning out the lights. That’s according to a study reported on February 14 in Current Biology, a Cell Press publication, in which researchers examined kittens with a visual impairment known as amblyopia before and after they spent 10 days in complete darkness.

Researchers Kevin Duffy and Donald Mitchell of Dalhousie University in Canada believe that exposure to darkness causes some parts of the visual system to revert to an early stage in development, when there is greater flexibility.

"There may be ways to increase brain plasticity and recover from disorders such as amblyopia without drug intervention," Duffy says. "Immersion in total darkness seems to reset the visual brain to enable remarkable recovery."

Amblyopia affects about four percent of the general population and is thought to develop when the two eyes do not see equally well in early life, as the connections from the eyes to visual areas in the brain are still being refined. Left untreated, that imbalance of vision can lead to permanent vision loss.

In the new study, the researchers examined kittens with amblyopia induced by experimentally depriving them of visual input to one eye. After those animals were plunged into darkness, their vision made a profound and rapid recovery. Further examination suggested that the restoration of vision depends on the loss of neurofilaments that hold the visual system in place. With those stabilizing elements gone, the visual system becomes free to correct itself.

Darkness therapy holds promise for the treatment of children with amblyopia, the researchers say, but don’t try this at home. They think that the darkness must be absolute to work, with no stray light at any time. It is also important to address the original cause of the amblyopia first, and to ensure that a period of darkness will not harm an individual’s good eye.

The researchers are still working out just how much darkness is required, and for how long. Regardless, they say it is unlikely that a drug could ever adequately mimic the effects of darkness that they’ve seen.

"The advantage of a simple nonpharmacological sensory manipulation, such as a period of darkness, is that it may initiate changes in a constellation of molecules in a beneficial temporal order and in appropriate brain regions," they write.

Research finds protein that prevents light-induced retinal degeneration

Research led by Minghao Jin, PhD, Assistant Professor of Ophthalmology and Neuroscience at the LSU Health Sciences Center New Orleans Neuroscience Center of Excellence, has found a protein that protects retinal photoreceptor cells from degeneration caused by light damage. This protein may provide a new therapeutic target for both an inherited retinal degenerative disease and age-related macular degeneration. The paper is published in the February 13, 2013 issue of the Journal of Neuroscience.

The visual cycle is essential for regenerating visual pigments that sense light for vision. However, abnormal visual cycles promote formation of toxic byproducts that contribute to the development of age-related macular degeneration (AMD), the leading cause of vision loss in elderly people that affects an estimated 2 million Americans. The mechanisms that regulate the visual cycle have been unclear. Identification and characterization of regulators of the visual cycle enzymes are critical for understanding these mechanisms.

RPE65 is a key enzyme involved in the visual cycle. RPE65 mutations have been linked to early onset vision loss, retinal degeneration, and blinding eye diseases. Despite such importance, the mechanisms that regulate the function of RPE65 are unknown. To identify and characterize previously unknown inhibitors of RPE65, the scientists tested five candidate proteins. Using gene screening, the LSUHSC research team discovered that one of them – fatty acid transport protein 4 (FATP4) – is a negative regulator; it inhibits RPE65.

"We found that FATP4 protects retinal photoreceptor cells from experimentally-induced retinal degeneration," notes Nicolas Bazan, MD, PhD, Boyd Professor, Ernest C. and Yvette C. Villere Endowed Chair of Retinal Degeneration, and Director of the LSU Health Sciences Center New Orleans Neuroscience Center of Excellence, who is a co-author of the paper.

Recently, mutations in the human FATP4 gene have been identified in patients with a certain recessive disorder which also features one of the toxic byproducts associated with abnormal visual cycles. This byproduct, called A2E accumulates in retinal pigment epithelial cells with age, prompting a call for further investigation to determine whether FATP4 mutations cause age-related vision impairment and retinal degeneration.

"These findings suggest that FATP4 may be a therapeutic target for the inherited retinal degenerative disease caused by RPE65 mutations and AMD," concludes Dr. Jin.

(Image: Eyeland Design Network)

Ontario man’s sight restored with help of stem cells

When Taylor Binns slowly began going blind because of complications with his contact lenses, he started to prepare for living the rest of his life without vision. But an innovative treatment using stem cells has changed all that, and returned to him the gift of sight.

Four years ago, while on a humanitarian work mission to Haiti, Binns developed intense eye pain and increasingly blurry vision. Doctors at home couldn’t figure out what was wrong and, over the next two years, Binns slowly went legally blind, no longer able to drive or read from his textbooks at Queens University, where he was studying commerce.

“Everything you could do before was being taken away, day by day, and it got worse and worse,” he recalls.

Doctors finally diagnosed him with a rare eye disease called corneal limbal stem cell deficiency, which was causing the normal cells on Binns’ corneas to be replaced with scar tissue, leading to painful eye ulcers that clouded over his corneas.

A variety of things can cause the condition, including chemical and thermal burns to the corneas, which are the glass “domes” over the coloured part of our eyes. But it’s also thought that microbial infections and wearing daily wear contact lenses for too long without properly disinfecting them can lead to the disease, too.

Since a corneal transplant was not an option for Binns, his doctors at Toronto Western Hospital proposed something new: a limbal stem cell transplant.