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Sleep Apnea May Play a Role in RVO

It might not be a coincidence that most people with retinal vein occlusion (RVO) discover their visual loss first thing in the morning, according to a study by French ophthalmologists. They found that 77 percent of the 30 RVO patients in whom they did detailed sleep studies had obstructive sleep apnea—more than 10 times the prevalence in the general population.

As they slept, these 23 people repeatedly stopped breathing for at least 10 seconds (apnea), or their nasal airflow decreased by at least half and blood oxygen saturation fell more than 3 percent (hypopnea). Episodes happened an average of 21.3 times per hour, stressing the retina in ways that are mostly unknown. “Our findings suggest that [obstructive sleep apnea] could be an additional risk factor that plays an important role in the pathogenesis of RVO or at least that it is a frequently associated condition that could be a triggering factor,” the group reports.1

Although the study was small and further research is needed, clinical ophthalmologists should take note, said Agnès Glacet-Bernard, MD, lead author of the article. “They should look for sleep apnea in every patient who has any type of retinal vein occlusion, especially if there is a history of snoring or daytime sleepiness,” said Dr. Glacet-Bernard, associate professor of ophthalmology at Intercommunal and Henri Mondor Hospitals, Paris-Est University. “Sleep apnea is largely underestimated. Usually patients are not aware that they have it and that their snoring and obstructed breathing puts them at risk for other health problems.” In the study, only one of the 23 cases of sleep apnea had been diagnosed previously.

Obstructive sleep apnea is known to raise the risk of abnormal glucose metabolism and cardiovascular diseases, including hypertension, heart attack and stroke. In the eye, the syndrome has been associated in small case studies with additional risk for retinal microaneurysms, impaired retinal blood flow, hypertensive retinopathy, and intraocular production of post-ischemic molecules associated with neovascularization, apoptosis and macular edema.

Dr. Glacet-Bernard and colleagues hypothesized two possible mechanisms by which apnea might affect blood and blood vessels, thus triggering RVO.

  • Hyperviscosity. “Hypoxia leads to dilation of vessels, and blood flow slows down. When that happens, there is aggregation of blood cells, hyperviscosity of the blood that can result in stasis, and possibly occlusion,” she said.
     
  • A jackhammer effect. “At the end of an apnea episode, there is an enormous release of catecholamines, and the patient wakes up slightly. This in turn leads to a peak in arterial tension, over and over again, throughout the night. The peak arterial tension may occur 100 or more times each night,” she said.

Known risk factors for obstructive sleep apnea include age older than 40, male gender, obesity and anatomical factors such as a thick neck. But experts stress that obstructive pharyngeal anatomy also occurs in other demographic groups, without obvious risk factors.

The prevalence of obstructive sleep apnea is variously estimated at 2 percent to 7 percent in both U.S. and international studies. Surprised at their 77 percent figure, the French research team looked for confounding factors but found none. They added that, even if the 33 RVO patients who served as controls for the study were assumed to be apnea-free and then added to the analysis, the prevalence would still be abnormally high at 37 percent.

If sleep apnea is proven to increase the risk for RVO, U.S. ophthalmologists would have a big problem ahead—much bigger than in France. Whereas 10.5 percent of the French are obese (BMI = 30) and 26.5 percent are overweight (BMI 25 to 30),2 in the United States 34 percent are obese and another 34 percent are overweight.3

—Linda Roach   

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1 Glacet-Bernard, A. et al. Arch Ophthalmol 2010;128(12):1533–1538.
2 www.oecd-ilibrary.org, choose “Factbook” then “Quality of Life.” Next to “Obesity,” select the PDF.
3 www.cdc.gov/nchs, choose “FastStats” and “Obesity/Overweight.”

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Amblyopia Update 

Acupuncture May Best Patching Therapy

Children between the ages of 7 and 12 with anisometropic amblyopia experienced a substantial improvement in visual acuity within 25 weeks when treated with acupuncture, according to Chinese researchers at the Joint Shantou International Eye Center of Shantou University and The Chinese University of Hong Kong.1

The study’s results showed that the 15-week best-corrected visual acuity (BCVA) for the acupuncture group improved by an average of 2.27 logMAR lines compared with 1.83 lines in the patching group.

And the resolution rate in the acupuncture group (41.5 percent) at 15 weeks was significantly better than in the patching group (16.7 percent; p = 0.01).

Although acupuncture has been used for treating various ophthalmic disorders, including dry eye, myopia and amblyopia, this single-center randomized controlled trial was the first of its kind to compare the effectiveness of acupuncture with conventional therapies for amblyopia. Thirty-eight girls and 50 boys were randomly assigned to either two hours a day of patching the sound eye or five sessions each week of acupuncture. All patients received constant optical correction and daily one-hour sessions of near-vision activities. “Our results are very encouraging. We found that acupuncture, when administered five times per week, was statistically superior to patching, potentially making it a good alternative treatment for amblyopia,” said Dennis S. C. Lam, MD, coauthor of the study and professor and chairman of ophthalmology and visual sciences at the Chinese University of Hong Kong.

And, although effective, this treatment regime is very time-consuming, he said. “It is therefore worthwhile to investigate whether the treatment routine could be optimized by reducing treatment frequency and duration—thus decreasing the total number of hospital visits.” For example, he indicated that whether or not five acupuncture sessions performed on three days, rather than five days per week, will generate similar outcomes deserves further investigation—and that it is important to determine whether or not part of the treatment can be conducted at home, such as applying acupressure at the therapeutic acupoints.

“We should be open-minded to new and alternative treatments such as acupuncture for amblyopia,” said Dr. Lam. “Furthermore, the effect of acupuncture should be evaluated in a data-driven and evidence-based manner.”

Because his group found that acupuncture and patching had equivalent treatment effectiveness, they have a follow-up study to investigate whether a combined treatment regimen of acupuncture and patching has a synergistic effect, producing a superior outcome that neither acupuncture nor patching alone can achieve.

—Leslie Burling-Phillips   

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1 Zhou, J. et al. Arch Ophthalmol 2010;128(12):1510–1517.

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Retina Report 

Good Glycemic Control May Have a Downside

A team of Danish researchers may have discovered the pathogenesis of diabetic papillopathy, which has been unknown until now. Their retrospective survey of type 1 diabetes patients identified tight glycemic control as the possible trigger of bilateral diabetic papillopathy (BDP).1 A small cup-to-disc diameter ratio appears to be a contributing risk factor.

Diabetic papillopathy, an optic disc edema of no detectable cause other than diabetes, may be unilateral or bilateral. The study considered only bilaterality, to help exclude other diagnoses. And it was restricted to type 1 diabetes, which has a clearly defined onset.

The study included 2,066 patients who were enrolled in a diabetic retinopathy screening program at the Steno Diabetes Center in Denmark between January 2001 and December 2008. It was designed to test the hypothesis that diabetic papillopathy may follow rapidly improved metabolic control.

Previous studies had already identified that some diabetes patients develop accelerated retinopathy progression in the first year of tight glycemic control, a phenomenon called “early worsening of diabetic retinopathy.”2,3 A similar finding was observed in the BDP study, said lead author Christoffer Ostri, MD, a resident ophthalmologist at Glostrup University Hospital in Copenhagen.

In the BDP study, metabolic control was determined by HbA1c values measured at three-month intervals. Normally, higher rates of glycated hemoglobin in the blood could lead to complications from diabetes, but in this study metabolic control had a downside. BDP was observed in five cases following a reduction of serum glucose.

In the overall study population, the trend toward a decrease in glycemic levels was –0.04 percentage points per quarter year. But the change rate in the five BDP patients before the incident was significantly higher, averaging –2.5 percentage points per quarter year.

What’s more, three of the five cases had concurrent progression of diabetic retinopathy. “We think that the same mechanisms may be involved,” possibly a deficit of adaptation, said Dr. Ostri.

An earlier study by The Diabetes Control and Complications Trial Research Group showed the benefits of glycemic control outweighed the worsening effects after one or two years. Similarly, Dr. Ostri said, “We found BDP to last for one year on average.” However, the small number of patient cases precludes drawing solid conclusions about edema duration, he said, adding that BDP resolves over time, with varying degrees of optic nerve damage.

While the BDP study points to less stringent glycemic control as a preventive measure, Dr. Ostri said that raising blood sugar in four of the five cases failed to yield any clear effect on diabetic papillopathy.

Since patients with type 1 diabetes with a cup-to-disc diameter ratio of 0.18 or less were at greater risk of BDP, Dr. Ostri suggests that precautions should be taken if patients have small cup-to-disc ratios. In such cases, endocrinologists could oversee a gentler lowering of glycemic levels, he said.

A follow-up study is planned. It is expected to include more cases of BDP that the researchers identified from the same population. And they are considering expanding their investigation to include type 2 diabetes patients because newer, potent, oral antiglycemic agents can lower blood sugar levels very rapidly, Dr. Ostri said.

—Miriam Karmel   

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1 Ostri, C. et al. Ophthalmology 2010;117(11):2214–2217.
2 Diabetes Control and Complications Trial Research Group. Arch Ophthalmol 1998;116:874–886.
3 Lauritzen, T. et al. Lancet 1983;1:200–204.

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