What clinicians learned from OHTS, EMGT

January 1, 2005

New Orleans-Lowering IOP in patients with ocular hypertension or early glaucoma does help delay or prevent further damage. However, does every 1 mm Hg of pressure reduction really affect patient outcomes?

That was the question that Gregg A. Heatley, MD, associate professor and vice chairman, University of Wisconsin-Madison, was asked to answer during the American Glaucoma Society subspecialty day at the American Academy of Ophthalmology meeting.

First, he reviewed the results of the Ocular Hypertension Treatment Study (OHTS) and the Early Manifest Glaucoma Trial (EMGT). In the OHTS, about 1,600 patients with ocular hypertension were randomly assigned to glaucoma drops to lower pressure by at least 20% or given no treatment. At 5 years follow-up, those treated with medication had half the rate of new visual field loss or optic disc damage (4.4%) compared with the control group (9.5%).

"The EMGT reached the same conclusion as the OHTS," Dr. Heatley explained. "Lowering pressure does indeed make a difference in outcomes in patients with early glaucoma and ocular hypertension."

Answering the harder question Then Dr. Heatley posed the more difficult question: "Does each and every 1 mm Hg truly count? In other words, do we have reason to believe that each and every unit change of pressure produces a unit of effect of outcome?"

Maybe it would be advantageous to look for other examples where one might expect to find a direct correlation between cause and outcome, Dr. Heatley suggested. He searched the literature on four topics:

Studies show that high doses of radiation increase the risk of mutation/cancer in a linear fashion. However, at low doses of radiation, the answer is not so evident. He noted that patients with no known exposure to radiation above normal daily levels still developed mutations. It isn't clear if every unit of radiation counts, he noted.

In the case of speed and rate of traffic accidents, one might assume that every mph increase would put one at higher risk for an accident. Not true. Dr. Heatley discovered that there are more vehicle accidents at slower speeds than higher speeds.

"It turns out that it is not the actual speed of travel that matters most, it is the difference of speed compared with the surrounding vehicles," he said.

Could there be a direct correlation between serum cholesterol and risk of stroke? Apparently not. Several reports showed that in patients with blood pressure in the normal range, there was no increased risk of hemorrhagic or ischemic stroke regardless of cholesterol level, Dr. Heatley said.

At the University of Wisconsin, researchers found that caloric restriction did help with longevity in a mouse model. However, the death rate also increased with too little caloric intake.

"There exists an asymptote where that next calorie does not affect mortality much, if at all. Not every calorie counts," he said.

In these examples, one might have thought that there would be a direct correlation between cause and outcome, but there was not.

"Why should we think that IOP is any different?" Dr. Heatley asked.

In April 2004, Ventura and Porciatti reported that lowering IOP in patients with different types of glaucoma had a positive effect on pattern ERG function, which improved from 40% to 150%. They found that this effect wasn't observed in non-glaucomatous eyes.