Optic Nerve Disease May Cause Sleep Disorders

In the February issue of the journal Ophthalmology, the investigators report on a study involving 25 students, ages 12 to 20, from the Missouri School for the Blind and 12 students with normal sight from the Thomas Jefferson School, a boarding school in suburban St. Louis. The visually impaired students were divided into two groups: Those whose visual problems were related to optic nerve disease and those whose vision loss did not involve the optic nerve. The optic nerve is made up of ganglion cells, the type of cells targeted by eye diseases such as glaucoma.

Participants with optic nerve disease were 20 times more likely to be pathologically sleepy (napping 20 or more minutes per day) than those with normal sight. They also were nine times more likely to have pathologic sleepiness than children who were blind from non-optic nerve diseases.

"We suspect these patients have difficulty using daylight to synchronize their internal rhythms to the outside world," says senior investigator Russell N. Van Gelder, M.D., Ph.D., assistant professor of ophthalmology and visual sciences and of molecular biology and pharmacology at the School of Medicine.

In recent research, Van Gelder found that the retina contains not only the photoreceptor cells called rods and cones, which translate light into vision, but it also houses non-visual photoreceptor cells called intrinsically photosensitive retinal ganglion cells (ipRG cells) that function as the eye's "light meter."

In a camera, the light meter helps a photographer determine how to set the shutter speed and whether to use a flash. By determining light levels, ipRG cells help synchronize the body's sleep/wake cycle, reset the internal body clock, control the pupil of the eye's response to light and regulate the release of hormones such as melatonin. These ipRG cells continue to gather and use information about light even in animals that otherwise are visually blind.

"In our basic research, we have demonstrated that animals that lack rods and cones in the retina still have very normal circadian, or body clock, functions," he says. "But animals that lack the ganglion, or 'light meter' cells cannot synchronize their clocks to the outside world."

The ipRG cells that act as the eye's light meter are concentrated together at the head of the optic nerve, so Van Gelder's team wondered whether children with optic nerve disease might have problems regulating their internal body clocks. To measure the impact of the loss of those cells, first author Raymond Wee, a graduate student in Van Gelder's laboratory, had participants wear a device known as a wrist-worn actigraph. Worn like a watch, the actigraph measures every movement a person makes. A sophisticated computer algorithm then uses this movement information to determine whether a person was awake or asleep, active or inactive. Children in the study wore the actigraphs every day for two weeks.

Those with optic nerve disease had highly variable wake-up times and also had trouble falling asleep, compared to blind children without optic nerve damage and sighted children. Those sleep problems led them to nap more frequently, and children with optic nerve disease napped, on average, about 28 minutes a day.

None of the children in the study had any other conditions that might contribute to sleep disorders. None took sedative drugs, had attention-deficit hyperactivity disorder (ADHD) or were being treated with stimulant medications. So, the researchers believe the sleep problems these children experienced were directly related to their eye disease.

"Taken together, these results lead to the unexpected conclusion that eye disease can be a risk factor for sleep disorders, and the health of the optic nerve strongly influences risk," Van Gelder says.

In future studies, Van Gelder hopes to test whether treatment with melatonin helps regulate sleep patterns in children with optic nerve disease. Melatonin is a naturally occurring hormone that helps regulate the circadian clock. Its release is related to the eye's light meter function.

But even before he learns whether it's possible to help these patients to synchronize their internal clocks to the outside world, Van Gelder believes it is important for health professionals to begin considering the impact of eye disease on sleep.

"Physicians and other health-care professionals should be sensitive to the possibility of daytime sleepiness or insomnia, particularly in patients with severe optic nerve disease," Van Gelder says. "Your eye doctor might want to make a point of asking how you've been sleeping."

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Wee R, Van Gelder RN. Sleep disturbances in young subjects with visual dysfunction. Ophthalmology, 111:2 pp. 297-302, Feb 2004.

This research was supported by grants from the Doris Duke Foundation, Research to Prevent Blindness, the Becker/Association of University Professors of Ophthalmology/Research to Prevent Blindness Physician-Scientist Award, the Culpepper Physician-Scientist Award, the National Alliance for Schizophrenia and Affective Disorders and the National Eye Institute of the National Institutes of Health.