Other factors play role in improving diagnosis, management of NTG

By Cheryl Guttman Krader

IOP remains the only proven modifiable risk factor for progression of normal-tension glaucoma (NTG), but there is some compelling evidence that a number of other variables play a role, according to Shan Lin, MD.

Dr. Lin reviewed information from studies investigating cerebrospinal fluid (CSF) pressure, myopia, sleep apnea, low blood pressure (BP), oxidant minerals (calcium and iron), and oral contraceptive (OC) use.

“This is by no means an exhaustive list of potential risk factors for glaucoma,” said Dr. Lin, professor of ophthalmology and director of the glaucoma service, University of California, San Francisco. “However, there is probably the most evidence for these factors, and several may be worth considering in patients with NTG that appears to be progressing despite your best efforts to keep IOP under control.”

From the list he presented, low BP, which would result in low ocular perfusion pressure (OPP), probably represents the most modifiable factor. Studies reporting an association between low OPP and glaucoma development/progression include the Barbados Eye Study and the Early Manifest Glaucoma Trial.

“Low BP may be due to overtreatment with systemic antihypertensive medication,” Dr. Lin said. “We should be measuring BP in our NTG patients and if it is low, coordinate care with the patient’s primary physician.”

Sleep apnea explored

Sleep apnea is another issue Dr. Lin explores in his glaucoma patients, even though there is some conflicting data on an association between sleep apnea and glaucoma.

“Nevertheless, I am surprised by the number of my patients with NTG who say they have sleep apnea, and if they are not already being treated, I refer them for a sleep evaluation,” Dr. Lin added. “Now, it will be interesting to see what future research shows about sleep apnea and glaucoma and whether treatment of sleep apnea prevents glaucoma progression.”

Dr. Lin has also begun to ask women with glaucoma about OC use. An association between OCs and glaucoma was first reported in an analysis of data from the Nurses Health Study that showed a 25% higher incidence of glaucoma among women who used OCs for at least 5 years. In a population-based study that is in press, Dr. Lin and colleagues found a 2-fold increase in glaucoma prevalence among women who had used OCs for more than 3 years.

Other recent research from Dr. Lin and colleagues points to an association between glaucoma and excessive supplemental intake of calcium and iron. He noted that the oxidant activity of these minerals provides a scientific basis for understanding how excessive doses could have detrimental health consequences. Triggering of retinal ganglion cell apoptosis by excessive calcium is one of several potential mechanisms that may be involved.

“Interestingly, our research also found a protective effect of higher dietary consumption of calcium and iron,” Dr. Lin pointed out. “However, the explanation for these seemingly contradictory results may be that high doses in the form of supplement ingestion cause spikes in calcium or iron levels that lead to detrimental effects.”

Implications with myopia

Discussing myopia, Dr. Lin noted that it may not be a target for intervention for preventing glaucoma once a patient is in adulthood. Nevertheless, it has relevance to clinical care because of its diagnostic implications.

He noted that analyses of data from the Australian Blue Mountains Eye Study and the Beijing Eye Study showed that myopes had an increased risk of glaucoma compared with emmetropic or non-myopic eyes. More recently, Dr. Lin and colleagues published their results from a U.S. population study.

While they found no association between myopia and either self-reported glaucoma or glaucoma diagnosed based on optic disc appearance, myopes were significantly more likely than emmetropes to have visual field defects; the level of increased risk was related to the level of myopia and ranged from 2.2-fold among mild myopes to 14.4-fold in those with severe myopia.

“It is unclear whether all of the visual field defects were glaucomatous or if some were myopia-related,” Dr. Lin said. “Nevertheless, our findings are compelling evidence that clinicians may be missing glaucoma in some high myopes.”

Dr. Lin noted that like myopia, CSF pressure is not a modifiable factor. However, research showing a relationship between CSF pressure and glaucoma is of interest because the information suggests a possible mechanism for the development of glaucomatous optic nerve damage.