Healthy Diet May Reduce Risk for Exfoliation Glaucoma

Miriam E. Tucker

March 04, 2014

WASHINGTON, DC — High folate intake is associated with a reduced risk for exfoliation glaucoma, according to an analysis of data from 2 large prospective cohort studies.

"Normalizing folate levels by eating a diet high in fruits and vegetables may reduce the risk of exfoliation glaucoma," said Louis Pasquale, MD, associate professor of ophthalmology at Harvard Medical School and director of the glaucoma service at the Massachusetts Eye and Ear Infirmary in Boston.

He presented the results here at the American Glaucoma Society 24th Annual Meeting.

"Since exfoliation glaucoma is very common in some populations, all patients would benefit from increasing their folate consumption to the recommended daily allowance of 400 µg per day simply by consuming fruit and vegetables," Dr. Pasquale, who is also codirector of the Harvard Glaucoma Center of Excellence, told Medscape Medical News.

Session moderator George Cioffi, MD, chair of the Department of Ophthalmology and director of the Edward S. Harkness Eye Institute at New York Presbyterian Hospital/Columbia University Medical Center in New York City, praised the study and called Dr. Pasquale and his group "probably the leading experts in the world in exfoliation glaucoma."

"It was good that they were careful enough not just to pursue the B vitamins, but also folate. I think we're starting to tease apart a system that we don't have all the answers for. But now we've got some genetic markers and blood levels of things like homocysteine and folate that are modifiable environmental factors," Dr. Cioffi told Medscape Medical News.

However, he cautioned, "every time we tease out an environmental exposure, it's not a causative experiment, so the causal relationship is not identified. That said, this is a big step."

Homocysteine and Exfoliation

Exfoliation glaucoma arises from exfoliation syndrome, an extracellular matrix disorder characterized by early cataract and secondary glaucoma. It often involves systemic manifestations, including sensorineural hearing loss, cardiovascular disease, and stroke.

In exfoliation glaucoma, there is an accumulation of large molecules on the surface of cells in the anterior segment of the eye. This material dislodges and clogs the internal drainage system of the eye, leading to elevated intraocular pressure and optic nerve damage. It is believed that elevated homocysteine contributes to this accumulation of material on the surface of intraocular cells, although the mechanisms of action are not entirely clear, Dr. Pasquale explained.

Previous research has strongly linked elevated serum homocysteine levels to exfoliation glaucoma. One meta-analysis found a correlation between high serum homocysteine levels and exfoliation glaucoma (Graefes Arch Clin Exp Ophthalmol. 2012;250:1067-1074). In addition, reduced levels of folate, which reduce homocysteine, were associated with an increased risk for the condition, but serum vitamins B6 and B12 were not.

Folate Findings

In their analysis, Dr. Pasquale and colleagues evaluated follow-up data from 78,980 women enrolled in the Nurses' Health Study from 1980 to 2010 and from 41,221 men enrolled in the Health Professionals Follow-up Study from 1986 to 2010. At baseline, all subjects were at least 40 years old and had no history of glaucoma or cancer.

In those studies, participants were asked every 2 years whether they had received a diagnosis of glaucoma. The diagnosing eye care practitioner and patient records provided confirmation of the condition.

Patients with definite exfoliation glaucoma had exfoliation material on the slit-lamp exam, 2 or more reliable visual fields, and reproducible loss. Patients with suspected exfoliation glaucoma met the slit-lamp criteria plus had an intraocular pressure above 21 mm Hg, a cup-to-disc ratio of at least 0.6, or at least 1 reliable abnormal visual field consistent with glaucoma.

Dietary folate was assessed every 2 to 4 years with a food frequency questionnaire.

Over the study period, 329 women and 70 men developed either definite or suspected exfoliation glaucoma. Mean intraocular pressure in the women was 28 mm Hg and in the men was 29 mm Hg.

The right eye was affected in about one third of the cohort, the left eye was affected in about one third, and both eyes were affected in about one third.

Interestingly, over 50% of the cohort, which consisted of healthcare professionals, was not getting the recommended 400 µg daily intake of folate, Dr. Pasquale noted.

On age-adjusted and multivariate analyses, no association was found between total vitamin B6 or vitamin B12 intake and exfoliation glaucoma, either definite or suspected.

However, there was a significant inverse trend for increased folate intake and reduced risk for definite or suspected exfoliation glaucoma. Risk was 25% lower for those in the highest quintile of folate intake (at least 650 μg/day) than for those in the lowest quintile (P trend = .02). This relation barely missed statistical significance, because "the confidence interval did cross 1.0, slightly," Dr. Pasquale reported.

Eating Fruits and Veggies

"More research is needed to understand how elevated homocysteine levels contribute to the development of exfoliation glaucoma," Dr. Pasquale told Medscape Medical News. "This is clearly an important path forward in understanding this disease at the molecular level. Fresh fruit and vegetables are a major source of dietary folate, and given their other health benefits, consumption of these food groups should be reinforced."

Dr. Cioffi said that although he often recommends green leafy vegetables to his patients, he is generally cautious about new association data. "I think there is harm in telling a patient to chase various bits of evidence," he said. "One day coffee is good for you, the next day it's bad for you. I don't modify patient care based on the first association study. But this is as good an association study as you're going to get, so it got my attention."

As for the finding that 50% of healthcare professionals aren't getting enough folate, Dr. Cioffi noted that, "just like everybody else, none of us eat very well. That's not surprising at all."

Dr. Pasquale and Dr. Cioffi have disclosed no relevant financial relationships.

American Glaucoma Society (AGS) 24th Annual Meeting: Abstract 21. Presented March 1, 2014.

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