Promising therapy for ‘eye stroke’

At first, Christine Jablonski didn’t worry about the blurry vision in her right eye. She dismissed it as a flake of morning mascara and went about her daily business in Ellicott City. But within two hours, the eye went dark.

She rushed to Johns Hopkins Hospital, where doctors told her there was nothing they could do to restore her vision – she had suffered an “eye stroke” from a clot blocking a key blood vessel that supplies the retina.

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But her daughter, a doctor, had heard about an experimental treatment pioneered by doctors at Hopkins’ Wilmer Eye Institute. The hospital’s Brain Attack Team, a group of physicians who specialize in strokes of the brain, was called in. They ran a catheter all the way from Jablonski’s groin to her eyeball and injected a clot-busting agent.

“I could see my vision coming back. It was like a curtain of color,” Jablonski said. Within two hours, her eyesight had returned to normal.

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Her experience and reports of success with other volunteers in a seven-year Hopkins study raise hopes for up to 50,000 people who suffer eye strokes each year and would otherwise face irreversible loss of sight in one eye.

But Hopkins doctors caution that the experimental procedure carries its own serious risks, and success seems to depend on getting the patient into treatment as soon as possible. It didn’t work at all on almost 25 percent of patients in the study, and other authorities say more trials are necessary before they can recommend the procedure.

Still, the Hopkins team was heartened by the results: Their volunteers were 13 times more likely than those undergoing conventional therapies to show significant improvement with standard eye charts. And they were almost five times as likely to achieve a final visual acuity of 20/100 or better on a 20/20 scale.

“We have a disorder that was basically irreversible, but with our technique, we see that a majority of patients experienced some level of improvement in their vision,” said Dr. Eric Aldrich, a neurologist at the School of Medicine and lead author of a study published in the June issue of the journal Stroke. “No one has ever reported these types of results on such a large scale in North America.”

An eye stoke, technically known as a central retinal artery occlusion, occurs when a clot forms in a small blood vessel within the eye. The interruption of blood flow destroys the retina, the light-sensitive nerve layer that captures images. The attack is sudden and painless, but it causes partial or complete vision loss in one eye. The other eye is usually unaffected.

Eye stroke is more likely to occur in the elderly, Hopkins researchers said. The condition appears to have the same heightened risk factors as brain stroke and heart disease. Those include diabetes, high blood pressure, elevated cholesterol levels, smoking and a family history of cardiovascular problems.

Under Aldrich’s direction, a team of ophthalmologists, radiologists and neurologists developed a scheme to insert tissue plasminogen activator (TPA), a clot-dissolving agent, into an artery near the eye. They start by inserting a catheter into the patient’s femoral artery in the thigh. Then, using an X-ray video display to show the way, they thread the tube up the bloodstream to the eye, where they administer TPA by drip until the blood clot dissolves.

From 1999 to 2006, 21 patients received TPA, while another 21 in their study received conventional therapies. Overall, 76 percent of the TPA group improved their vision by at least one line on the Snellen chart – the eye chart with the big “E” at the top. Only 33 percent in the standard therapies group showed that much improvement.

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In addition, a third of volunteers in the TPA group experienced an improvement of three lines or better, compared with 5 percent of patients in the standard group.

“This was a condition that has never had any useful treatment. We have done things to help the eye reduce the pressure, but none really work to any degree,” said Dr. Neil Miller, the team’s lead ophthalmologist. “Most patients end up blind or nearly so.”

Current FDA-approved therapies include paracentesis (sticking a needle into the eye and withdrawing fluid), breathing a mixture of carbon dioxide and oxygen gas, and eye massage. All are designed to restore blood flow, but none works well.

TPA is typically used to treat stroke and heart attacks, but in 1996, German researchers tried it on eye stroke victims for the first time. Hopkins researchers modified the technique to reduce the length of the procedure, the quantity of drug used and the danger of complications, which can include bleeding, damage to arteries and stroke.

All of the team’s patients were treated within 15 hours of losing vision. The time element is critical, Aldrich says, because the eye tissue dies gradually over the next few hours.

“Time is retina. If you restore blood to the tissue sooner, then you have a greater chance of recovery,” Aldrich said.

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The time factor might have saved Jablonski’s eyesight in April 2001. The Ellicott City resident, now 68, was on her way to the dry cleaners when she realized she had something far more serious than a speck of mascara in her eye. She called her husband, who took her to Hopkins.

There, doctors from Wilmer stuck a needle in her eye to relieve the pressure but told her there was no way to save her eyesight.

“I never thought this would happen to me,” said Jablonski, a retired nurse. “I’m not overweight. I eat well. I exercise.”

But her daughter, Dr. Donna Perlin, who was working a shift in Hopkins’ pediatric emergency room, asked doctors about TPA treatment. They called Aldrich and the Brain Attack Team.

“I asked a doctor on the team, ‘What would you do if it were your mother?’ ” said Perlin, now 44 and a pediatric emergency medicine physician at Vanderbilt University in Nashville.

“And he said, ‘I would go for it.’ So we went for it.”

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Within 10 hours of losing vision, Jablonski was receiving TPA treatment. Afterward, she recovered in the hospital for several days and left with 20/40 vision – her original eyesight.

“The procedure was very traumatic, and I didn’t know whether I would throw another clot,” Jablonski said. “But I recovered very quickly and am so grateful to the doctors.”

Others in the Hopkins study weren’t so fortunate: Five out of 21 patients who received TPA saw no improvement and remained essentially blind in one eye. Researchers speculate that patients who received TPA later or already suffered from extensive arteriosclerosis (hardening of the arteries) did not respond as well.

Some doctors also caution that the procedure poses its own dangers -including stroke and heart attack – since the catheter works its way through major arteries. “Not all institutions can offer this therapy. They would need very well-trained interventionalists,” Miller said. “But the risks are decreased in experienced hands.”

One ophthalmologist who wasn’t involved in the study called it well-designed and informative. But he wouldn’t recommend the treatment with absolute confidence.

“There’s no definitive conclusion from the study,” said Dr. George Williams, a spokesman for the American Academy of Ophthalmology and chairman of the department of ophthalmology at Beaumont Hospital in Royal Oak, Mich. “The data, although promising, warrants further investigation.”

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He said he would prefer randomized trials with more patients but acknowledged the difficulty in managing such trials, given the rarity of the condition.

“We have one of the busiest hospitals in the U.S., and it took seven years to get 42 patients,” Williams said of the Hopkins study.

Volunteers who arrived more than 15 hours after losing their vision were automatically given standard therapies instead of TPA. That might have skewed the results in favor of the experimental treatment, he said.

In addition, Williams said, he wanted to know more about exactly how well the patients could see before and after the operation – instead of the relative improvement in eyesight that Hopkins reported.

“If the alternative is total blindness, then 20/200 is a great result,” he said. “But if patients are initially presenting with better vision than that, then is that enough improvement to justify the expense and the risk of the procedure?”

For their part, Hopkins researchers said their main concern was improvement in vision – they will address specific visual acuity the next time around. Their next step is controlled, randomized, multicenter trials to confirm their initial success and address the safety of the treatment.

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For patients, they say, the most important message from the report is recognizing the warning signs of an eye stroke.

“If you lose vision abruptly, you need to go to the ER right away,” Miller said. “Do not wait until the next day to see an ophthalmologist, because then it may be too late.”

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