Glaucoma biomarkers under study

September 15, 2010

The relationship between IOP and scleral response could serve as a biomarker for glaucoma and represents one direction glaucoma research is taking.

Biomarker studies investigating this complex relationship could be particularly important because half or more of the people with open-angle glaucoma never have an eye pressure above normal, said Harry A. Quigley, MD, at the annual meeting of the Association for Research in Vision and Ophthalmology.

"We should no longer be surprised that open-angle glaucoma happens to people with normal pressure," said Dr. Quigley, the A. Edward Maumenee Professor of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore.

Future directions

The ability to measure scleral stiffness would be helpful, although currently there is no method of doing this in living eyes.

Researchers at several centers are developing methods to measure scleral stiffness indirectly, and as technology improves it may be possible within a few years to measure the stiffness of the sclera and changes in the behavior of the lamina cribrosa directly in response to changes in eye pressure, Dr. Quigley said. This accomplishment might make it possible to use IOP change as a biomarker.

Another avenue of research would be to determine whether the mean level of IOP or the degree of fluctuation is the more important biomarker indicator.

"Our ability to measure the IOP on a continuous basis represents a very important second future direction," Dr. Quigley said. "It's only when we have continuous readout of eye pressures that we're finally going to understand much more about the risk of IOP."

He also said that ophthalmologists are familiar with the concept of eye pressure pushing out on the optic nerve, a force opposed slightly by the cerebrospinal fluid pressure. However, engineering studies suggest that the behavior of the sclera is equally or even more important since the scleral in-plane stress that generates strain pulling outward on the lamina cribrosa may be a greater force. And this force may be potentially much more important in many humans in translating IOP stress to the axons.

In the eyes of human specimens that have changed due to glaucoma, the lamina cribrosa is pulled outward and compressed downward, he added. It is the outward stress behind Bruch's membrane that potentially generates damage to astrocytes, axons, and capillaries in the nerve head.

Dr. Quigley also commented on the recent discovery that there are at least two components to damage in the optic nerve head. The prelaminar loss of axons, where there is no connective tissue in the primate or human nerve head, is one component, and the deformation of the laminar cribrosa is the second. IOP is associated with both of those, but topography measurements assess both together, suggesting that the topography measurement is not a direct measure of ganglion cell loss but rather a measurement of both of those components.

According to Dr. Quigley, the pressure-related component of glaucoma would relate to the change in the sclera, but once the axons are injured, many other variables must be taken into account. And how well the ganglion cells tolerate the injury would not necessarily be related to an individual's IOP.

"The IOP component of glaucoma is not going to explain everything," Dr. Quigley said. "Nothing explains everything."