Eye Health Headlines

The eyes are the window into the soul — or at least the mind, according to a new paper published in Perspectives on Psychological Science, a journal of the Association for Psychological Science. Measuring the diameter of the pupil, the part of the eye that changes size to let in more light, can show what a person is paying attention to. Pupillometry, as it’s called, has been used in social psychology, clinical psychology, humans, animals, children, infants — and it should be used even more, the authors say.

The pupil is best known for changing size in reaction to light. In a dark room, your pupils open wide to let in more light; as soon as you step outside into the sunlight, the pupils shrink to pinpricks. This keeps the retina at the back of the eye from being overwhelmed by bright light. Something similar happens in response to psychological stimuli, says Bruno Laeng of the University of Oslo, who cowrote the paper with Sylvain Sirois of Université du Québec à Trois-Rivières and Gustaf Gredebäck of Uppsala University in Sweden. When someone sees something they want to pay closer attention to, the pupil enlarges. It’s not clear why this happens, Laeng says. “One idea is that, by essentially enlarging the field of the visual input, it’s beneficial to visual exploration,” he says.

However it works, psychological scientists can use the fact that people’s pupils widen when they see something they’re interested in.

Laeng has used pupil size to study people who had damage to the hippocampus, which usually causes very severe amnesia. Normally, if you show one of these patients a series of pictures, then take a short break, then show them another series of pictures, they don’t know which ones they’ve seen before and which ones are new. But Laeng measured patients’ pupils while they did this test and found that the patients did actually respond differently to the pictures they had seen before. “In a way, this is good news, because it shows that some of the brains of these patients, unknown to themselves, is actually capable of making the distinction,” he says.

Pupil measurement might also be useful for studying babies. Tiny infants can’t tell you what they’re paying attention to. “Developmental psychologists have used all kinds of methods to get this information without using language,” Laeng says. Seeing what babies are interested in can give clues to what they’re able to recognize — different shapes or sounds, for example. A researcher might show a child two images side by side and see which one they look at for longer. Measuring the size of a baby’s pupils could do the same without needing a comparison.

The technology already exists for measuring pupils — many modern psychology studies use eye-tracking technology, for example, to see what a subject is looking at, and Laeng and his coauthors hope to convince other psychological scientists to use this method.

Gene therapy for congenital blindness has taken another step forward, as researchers further improved vision in three adult patients previously treated in one eye. After receiving the same treatment in their other eye, the patients became better able to see in dim light, and two were able to navigate obstacles in low-light situations. No adverse effects occurred.

Neither the first treatment nor the readministered treatment triggered an immune reaction that cancelled the benefits of the inserted genes, as has occurred in human trials of gene therapy for other diseases. The current research targeted Leber congenital amaurosis (LCA), a retinal disease that progresses to total blindness by adulthood.

Scientists from The Children’s Hospital of Philadelphia and from the Perelman School of Medicine at the University of Pennsylvania led the study, recently published in Science Translational Medicine.

“Patients have told us how their lives have changed since receiving gene therapy,” said study co-leader Jean Bennett, M.D., Ph.D., F.M. Kirby professor of Ophthalmology at Penn. “They are able to walk around at night, go shopping for groceries and recognize people’s faces — all things they couldn’t do before. At the same time, we were able to objectively measure improvements in light sensitivity, side vision and other visual functions.”

Other objective results came from brain signals seen in neuroimaging. When a dimly flickering checkerboard pattern flashed in front of a patient’s recently treated eye, an area in the brain responsible for vision lit up during functional magnetic resonance imaging (fMRI).”This finding is telling us that the brain is responding to the eye’s sensitivity to dim light,” said radiology researcher Manzar Ashtari, Ph.D., of The Children’s Hospital of Philadelphia, the study’s co-leader.

LCA is a group of hereditary retinal diseases in which a gene mutation impairs production of an enzyme essential to light receptors in the retina. The study team injected patients with a vector, a genetically engineered adeno-associated virus, which carried a normal version of a gene called RPE65 that is mutated in one form of LCA.

The researchers in the current study previously carried out a clinical trial of this gene therapy in 12 patients with LCA, four of them children aged 11 and younger when they were treated. Exercising caution, the researchers treated only one eye — the one with worse vision. This trial, reported in October of 2009, achieved sustained and notable results, with six subjects improving enough to no longer be classified as legally blind.

The Center for Cellular and Molecular Therapeutics (CCMT) at The Children’s Hospital of Philadelphia sponsored both the initial clinical trial and the current study, and manufactured the vector used to carry the corrective gene. Katherine A. High, M.D., a co-author of both studies, is the director of the CCMT, and a pioneering gene therapy researcher.

The research team’s experiments in animals had showed that readministering treatment in a second eye was safe and effective. While these results were encouraging, the researchers were concerned that readministering the vector in the untreated eye of the patients might stimulate an inflammatory response that could reduce the initial benefits in the untreated eye.

“Our concern was that the first treatment might cause a vaccine-like immune response that could prime the individual’s immune system to react against a repeat exposure,” said Bennett. Because the eye is “immune-privileged” — relatively isolated from the body’s immune system — such a response was considered less likely than in other parts of the body, but the idea needed to be tested in practice.

As in the first study, retina specialist Albert M. Maguire, M.D., a study co-author, injected the vector into the untreated eyes of the three subjects at The Children’s Hospital of Philadelphia. The patients had been treated one and a half to three years previously.

The researchers continued to follow the three patients for six months after readministration. They found the most significant improvements were in light sensitivity, such as the pupil’s response to light over a range of intensities. Two of the three subjects were able to navigate an obstacle course in dim light, as captured in videos that accompanied the published study.

There were no safety problems and no significant immune responses. There was even an unexpected benefit — the fMRI results showed improved brain responses not just in the newly injected eye, but in the first one as well, possibly because the eyes were better able to coordinate with each other in fixating on objects.

The researchers caution that follow-up studies must be done over a longer period and with additional subjects before they can definitively state that readministering gene therapy for retinal disease is safe in humans. However, said Bennett, the findings bode well for treating the second eye in the remaining patients from the first trial — including children, who may have better results because their retinas have not degenerated as much as those of the adults.

Furthermore, Bennett added, the research holds promise for using a similar gene therapy approach for other retinal diseases. Ashtari said that fMRI may play a future role in helping to predict patients more likely to benefit from gene therapy for retinal disease.

We don’t see only what meets the eye. The visual system constantly takes in ambiguous stimuli, weighs its options, and decides what it perceives. This normally happens effortlessly. Sometimes, however, an ambiguity is persistent, and the visual system waffles on which perception is right. Such instances interest scientists because they help us understand how the eyes and the brain make sense of what we see.

Most scientists believe rivalry occurs only when there’s “spatial conflict” — two objects striking the same place on the retina at the same time as our eyes move. But the retina isn’t the only filter or organizer of visual information. There’s also the “non-retinal reference frame” — objects such as mountains or chairs that locate things in space and make the world appear stable even when our eyes are moving.

“We asked: what if visual ambiguities are not presented on the same spot on the retina, but on the objects [in the frame] as they move around,” says California Institute of Technology cognitive scientist Jeroen J.A. van Boxtel. Indeed, he and colleague Christof Koch found evidence of rivalry in this reference frame, with surprising effects on the better-understood spatial conflict. The findings, which will appear in an upcoming issue of Psychological Science, a journal published by the Association of Psychological Science, offer intriguing clues to how the visual system works.

In their experiments, van Boxtel and Koch created spatial conflict with a “motion quartet,” which changes the arrangement of four dots. If the dots are displaced in certain ways, the visual system isn’t sure if the movement is vertical or horizontal. If the dots move to an altogether different space, there’s no rivalry. Then the researchers upped the perceptual ante by creating an object reference frame with three white discs and shifting it, too, along with or in opposition to the smaller dots.

Seven male and female participants viewed the changing arrangements in four conditions. In one, both dots and discs remained stationary (creating spatial rivalry); in each of two, either dots or discs moved right or left; in the fourth, both moved horizontally together (creating ambiguity in the frame). Each time, participants had to press a button indicating whether the dots moved horizontally or vertically. The presses were analyzed for perceived movement “bias” (more horizontal or vertical) and duration — evidence either of rivalry or visual clarity.

The results: Even when the dots moved to another space altogether — so there was no spatial conflict — the moving discs created the effect of perceptual ambiguity. But the researchers also found that visual rivalry disappeared when the dots were stationary and the disks moved (that is, the dots were not linked to the disks). It was as if the brain had bigger fish — object-frame rivalry — to fry.

In subsequent experiments — one changing the vertical relationship of the dots and one placing the dots outside the white discs — the researchers got results similar to those they would have gotten without the frame. Their conclusion: The visual system is working out object-frame rivalry as it would spatial rivalry, probably with the same brain regions and processes.

When we gaze at a shape and then the shape disappears, a strange thing happens: We see an afterimage in the complementary color. Now a Japanese study has observed for the first time an equally strange illusion: The afterimage appears in a “complementary” shape — circles as hexagons, and vice-versa.

“The finding suggests that the afterimage is formed in the brain, not in the eye,” the author, Hiroyuki Ito of Kyushu University, wrote in an email. More specifically, the illusion is produced in the brain’s shape-processing visual cortex, not the eye’s light-receiving, message-sending retina. The findings appear in an upcoming issue of Psychological Science, a journal published by the Association for Psychological Science.

Ito conducted three experiments with 82, 92, and 44 participants respectively. In the first two, he showed participants yellow circles or hexagons — outlined or filled, static or rotating on a gray ground. In each, after they observed the images for 10 seconds, the images disappeared, leaving only the blank gray field. The observers were asked to indicate which of seven shapes, on a piece of paper, the afterimage most resembled.

In the third experiment, Ito split the visual field between the two eyes. In the left eye, participants saw rotating circles and hexagons, as well as rotating asterisk-like “stars” — shapes that were neither round nor angular. The right eye viewed static circles in all conditions. When the circles, hexagons, and stars disappeared, the left field was black, which suppressed the formation of afterimages, and the right was white, which heightened it.

In Experiments 1 and 2, participants tended to see circles after hexagons and hexagons after circles. In the third, the right eye produced the most angular afterimages when rotating circles had been projected in the left eye; the most rounded ones after the rotating hexagons; and after the “stars,” images that were neither circular nor edged.

How did Ito infer that the brain, not the eye, was producing these afterimages? He eliminated the theory that the afterimage was a manifestation of “retinal bleaching” — when the photoreceptors on the retina become ineffective or fatigued through prolonged exposure to light. Viewing static circles or hexagons produce circular or hexagonal bleached areas on the retina. However, the afterimage shapes were not in the bleached shapes. A spinning circle or hexagon produces a circular trace of light on the retina, causing circular shape of retinal bleaching just as painting on the retina. However, spinning circles produced hexagonal afterimages and vice versa.

Retinal bleaching could not produce “an afterimage shape different from the [typical] retinal bleaching shape.” Neither could the retina transfer information taken in by the left eye to produce an afterimage in the right eye. “The only site that can happen is the brain.”

The research adds to science’s understanding of the role of the brain in vision. “People tend to think that afterimages are meaningless by-products arising from the physiological characteristics of the eye,” wrote Ito. “But I think that the afterimages reflect brain activities and provide us the means to know those activities in a directly visible form.”