Glaucoma
March 2016

by Tony Realini, MD, MPH

Over the past 2 decades, numerous epidemiologic studies have revealed that normal tension glaucoma (NTG) represents a much higher proportion of all open-angle glaucoma than previously thought. These studies have also demonstrated significant regional variation in the prevalence of NTG. This was the focus of one of the glaucoma sessions at the 2016 World Ophthalmology Congress (WOC) in Guadalajara, Mexico.

“In Japan, 92% of open-angle glaucoma is NTG,” said Ki Ho Park, MD, Seoul, Korea. “In Korea, it is 95% according to a recent study from the Korea National Health and Nutrition Examination Survey.”

Makoto Araie, MD, Tokyo, agreed. “The prevalence of NTG is particularly high in eastern Asians and Hispanics. Although estimates vary widely between studies, taken together, epidemiologic studies suggest that throughout the world, NTG represents perhaps 50% or more of all open-angle glaucoma.”

“The more we look, the more we find,” Dr. Park said. “Retinal nerve fiber layer photography and optical coherence tomography (OCT) can detect normal tension glaucoma and its progression before the visual field changes.”

Who is at risk for NTG?

The risk factors for both the development of normal tension glaucoma and its progression have been evaluated in many studies. Most of these come from east Asian countries, where NTG is most prevalent and most easily studied.

“Risk factors for developing NTG in Japan and Korea are increasing intraocular pressure (IOP), myopia, and advancing age,” Dr. Park said. “In Korea, additional risk factors include male gender, systemic hypertension, and not being overweight. In younger people—those under age 40—additional risk factors include high fasting blood glucose and low HDL cholesterol.”

“Based on a study conducted in the United States, risk factors for progression of NTG include disc hemorrhage, female gender, and a history of migraine headaches,” he added.

Disc hemorrhages have long been considered an ominous sign of progression in NTG.

“Longitudinal detection of disc hemorrhages in open-angle glaucoma plateaus after 5 years,” Dr. Park said, “with 46% of NTG eyes and 23% of high tension open-angle glaucoma eyes manifesting one or more disc hemorrhages. This suggests that there is a specific subpopulation of glaucoma patients who are at risk for disc hemorrhages. The higher prevalence of disc hemorrhages in NTG versus HTG suggests the possibility that NTG eyes have a higher susceptibility of small blood vessels to rupture.”

Is sleep apnea an unrecognized risk factor?

The ongoing search for risk factors in glaucoma has recently revealed a new potential factor: obstructive sleep apnea.

“There is a very strong connection between obstructive sleep apnea and normal tension glaucoma,” said Robert Ritch, MD, New York. Based on a handful of small studies, estimates for the prevalence of sleep apnea among patients with NTG range from 6–50%, with obstructive sleep apnea increasing with age in cohorts of NTG patients.

Sleep apnea may directly contribute to the pathophysiology of NTG by inducing ischemia by reducing ocular perfusion pressure. “Sleep apnea occurs at night,” Dr. Ritch explained, “when IOP is typically at its highest and blood pressure at its lowest. These 3 separate risk factors for glaucoma are present simultaneously and are additive. I think NTG is primarily a nocturnal disorder.”

We may not be very good at identifying which of our patients have sleep apnea. “The typical patient with sleep apnea is an overweight male with a thick neck who consumes alcohol, particularly just before bedtime, and who snores,” Dr. Ritch said. “But many patients do not fit this risk pattern. Anyone can have sleep apnea.”

“It is important to know that at present, it is estimated that about 80% of obstructive sleep apnea patients remain undiagnosed as such,” Dr. Ritch said. “I order polysomnography on many of my NTG patients who are progressing despite what appears to be adequate IOP control and in whom nocturnal blood pressure overdipping has been ruled out.” He pointed out that treatments such as continuous positive airway pressure (CPAP) can reduce ischemia and may reduce glaucoma risk in patients with sleep apnea.

He also advised that patients with sleep apnea be screened for glaucoma.

NTG and the risk of blindness

Tetsuya Yamamoto, MD, Gifu, Japan, has conducted long-term analysis of patients with NTG. “The 20-year incidence of blindness in normal tension glaucoma is 9.9% in 1 eye and 1.5% in both eyes,” he said.

How can blindness be avoided? “Achieving a consistent IOP reduction of 20–30% is associated with a 93–96% probability of stable NTG without visual field progression over 15 years of treatment,” he explained. “Likewise, achieving target IOP of 1011 mm Hg confers a 90% or greater probability of NTG stability over 15 years.”

Is there an optimal modality for IOP reduction in NTG? Dr. Yamamoto thinks so. “Trabeculectomy is effective in achieving target IOP and stabilizing the visual field.”

He added, “Patients treated with medications achieved a mean IOP reduction of approximately 20%, which was associated with a 1.4-fold reduction in visual field progression. In contrast, patients treated with surgery achieved a mean 40% IOP reduction and a 5.7-fold slower rate of visual field progression. If medications alone fail to achieve target IOP reduction of at least 20–30%, surgery should be considered.”

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Editors’ note

The physicians have no financial interests related to their comments.

Contact information

Araie: araie-tky@umin.net
Park: kihopark@snu.ac.kr
Ritch: ritchmd@earthlink.net
Yamamoto: mmc-gif@umin.net