Focusing on Glaucoma Solutions

University of Alabama Birmingham, AL

The primary focus of diagnostic exams for glaucoma, and follow-up testing, is measuring pressure inside the eye. A rise in pressure indicates that the disease is worsening, and all current glaucoma treatments work by reducing that pressure. But, say researchers at the University of Alabama (UAB), intraocular pressure isn’t always a reliable indicator of a person’s risk.

Fig. 1 – J. Crawford Downs holds a model of the lamina cribosa, which UAB researchers created with a 3D printer.

Many patients with high pressure don’t develop glaucoma, while others with “normal” pressure do. The researchers noted that while access to health care and socioeconomic factors play a major role, racial differences in the structure where the optic nerve exits the eye can also predispose people of African descent to glaucoma.

Working with UAB Department of Ophthalmology, J. Crawford Downs, PhD, an internationally renowned glaucoma researcher at the Devers Eye Institute, Portland, OR, takes a biomechanics approach to the eye, using engineering principles to model the eye’s complexity and analyze its weak points.

Downs is particularly interested in a part of the optic nerve head known as the lamina cribrosa. This crucial structure, barely wider than a pencil lead, acts as a mechanical seal around the optic nerve as it passes out of the eye on its way to the brain. “It’s the place where Downs says. “We want to understand the mechanics of that structure and what it looks like in three dimensions.”

To do that, he invented and built a “fluorescent three-dimensional histologic reconstruction device.” The fully automated machine takes a section of tissue from a human donor eye and slices it into thousands of pieces, snapping a photo of each slice. These images are combined to generate a high-resolution, three-dimensional model of the donor’s lamina cribrosa at a volumetric resolution some five million times better than the most advanced MRI. (See Figure 1)

Once they have the model, the researchers put it in a computer, apply pressure to it, and examine the results, Downs explains.

By comparing models from patients of different races and ages, the researchers say that they are discovering new insights about the factors that make some patients more likely to suffer nerve damage, even at lower intraocular pressures.

Tracking Pressure

Another inventor in the Ophthalmology Department, Assistant Professor Massimo Fazio, PhD, has built a unique, ultra-precise device to track the eye’s response to pressure. It focuses four laser beams on a donor eye, which is immersed in a saline bath and can be inflated to simulate a range of eye pressures. One beam arrives slightly after the others, allowing the researchers to measure— at nanometric precision—the tiny, fleeting mechanical changes in the shape of the eye as it responds to changes in intraocular pressure. Four synchronized high-speed cameras record the data at 150 images per second.

Downs’s research showed that each time someone blinks or moves the eye, a wave of pressure rolls through the eye within a few milliseconds, forcing it to expand. The effects of these rapid shifts in pressure hadn’t been explored because, until now, scientists had not developed the right technology.

With his laser device, Fazio is now doing those studies on donor eyes from patients of different ages and races. “We are concerned that this pressure impulse is transferred to the posterior pole of the eye, and possibly to the optic nerve head,” he says. “Understanding the eye’s response to these highly variable mechanical events might be very important to understand what’s causing glaucoma—and eventually how to address and prevent it.”

The ultimate goal of all of this research, Downs says, is to develop a test that can identify patients at highest risk for glaucoma years before the disease begins to cause problems. “That’s the holy grail,” he says. “Glaucoma is very expensive to treat, and we have to treat many more people than need to be treated, because we don’t know who will go on to develop glaucoma and who won’t.”