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Wednesday, January 14, 2009

Spotting Cataracts Earlier

Seeing eye: A beam of light from a slit-lamp microscope focused on a cataract.
Credit: Manuel Datiles

Cataracts are the single biggest cause of blindness and are responsible for almost half of all cases worldwide. A new laser probe, originally developed for the U.S. space program, has been shown to detect the condition earlier than is otherwise possible. Its developers say that the technique can tell that a cataract is forming even when an eye looks perfectly clear.

Cataracts are caused by the buildup of damaged proteins within the eye's lens, clouding it over and impairing vision. "The proteins start to unravel when they are damaged, and stick together to form clumps," says Manuel Datiles, a medical officer and senior clinical investigator at the National Eye Institute, in Bethesda, MD, who has been assessing the new technique.

The protein buildup that causes cataracts can be triggered by age, but various stress factors, such as exposure to cigarette smoke and poor blood-sugar management in diabetics, contribute to the problem. Once cataracts have developed, the most common treatment is replacing the impaired lens with an artificial one. But if cataracts can be detected early enough, then it may be possible to slow or stop the accumulation of damaged proteins by reducing relevant factors, says Datiles.

Normally, diagnosis is carried out by looking for protein buildup in the eye with a slit-lamp microscope--a standard ophthalmological device that illuminates the eye with a beam of light so that it can be examined with a microscope. However, slit-lamp microscopes can only detect cataracts once they have formed, Datiles says. "This new method detects cataracts even before they can be detected normally, and before they are symptomatic," he notes.

The new technique uses dynamic light scattering (DLS) to detect small proteins called alpha crystallins in the eye's lens. These are known to play a natural role in preventing cataracts from forming by sticking to larger proteins and stopping them from unraveling. If the larger proteins cannot unravel, then they cannot stick together.

Cataracts can still form because there are only a finite number of these proteins in the eye, and they are gradually depleted. So these alpha crystallins can be a useful biomarker, Datiles says: "If the amount of alpha-crystallin proteins has dwindled, then you know something is happening."

Alpha-crystallin proteins are between one and three nanometers in diameter--too small to detect using conventional equipment. But DLS can spot them by measuring the way that light is reflected by particles in a liquid.

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DLS was originally developed to study protein crystal formation on the International Space Station (ISS), with the goal of exploring possible new drugs. "In space, due to the lack of gravity, you are able to do a better job of growing better-quality and bigger crystals," says Rafat Ansari, a senior scientist at NASA's John H. Glenn Research Center, in Cleveland. When Ansari's father developed cataracts and the NASA researcher learned the role that protein changes play in their formation, Ansari began to explore the use of DLS as a means of earlier detection.

Laser light is shone into the lens of the eye while a highly sensitive photon detector called an avalanche photodiode is used to measure light backscattered at specific wavelengths. Because alpha-crystallin proteins are much smaller than the proteins that make up cataracts, they move differently. "Brownian motion is effectively controlled by the size of the particles," says Ansari, so smaller particles will move faster than larger ones.

By tuning the photon detector to monitor specific wavelengths over a period of about five seconds, it is possible to accurately measure alpha-crystallin levels.

"Alpha-crystallins are a reliable biomarker for cataracts and demonstrating this in humans is an advance," says Krishna Sharma a professor of ophthalmology at the Mason Eye Institute in Columbia, MO. The process is tricky, Sharma says, because pigments within the lens can affect the visible light scattering back.

The device has so far been tested in a clinical trial involving 235 patients. "We had a whole range, from young people with perfectly clear lenses to older people," says Datiles. The results were recently published in the journal Archives of Ophthalmology. "We were surprised that we can detect the alpha-crystallin proteins in a clear lens even before a cataract has appeared," he says.

The group is now working on a longer-term National Institute of Health study to monitor alpha-crystallin levels in patients with existing cataracts. The hope is that the technique will eventually prevent cataracts from forming in the first place. "Our hope is that millions of people will benefit from this," says Datiles.