The Latest Research - Glaucoma Progression: Detection and Management

Management of glaucoma progression is an ongoing process requiring frequent surveillance and monitoring to prevent visual impairment and maintain the quality of life. Experts in a panel discussion of progression agreed on the importance of frequent testing and the use of computerized diagnostic tools to assist in the monitoring. The glaucoma experts participated in a continuing medical education symposium Saturday evening at the Sheraton New Orleans Hotel.

Although glaucoma is often thought of as a benign and very slowly progressing disease, it must be closely monitored and followed long-term. The rate of glaucomatous progression varies considerably between individuals, with some studies showing low mean progression rates and others extremely high rates. However, with long-term follow up and frequent testing, progression can be identified in most cases, said Anders Heijl, MD, PhD, professor and chairman of the ophthalmology department at Malmö University Hospital, Lund University, Malmö, Sweden.

Large clinical trials have provided information about the rates of progression among their study populations, but the important concern for the practicing physician?and for the patient?is the individual rate. With frequent testing, this rate can be estimated within approximately three years, Dr. Heijl said.

"We miss a lot of progression because we don't have enough data," he added.

New software for measuring and displaying disease progression simplifies this process, but disc photography remains an important and underused tool for detecting structural progression, said David S. Greenfield, MD, professor of ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller College of Medicine, Miami. Disc photography is used to assess the rim, cup, retinal nerve fiber layer, peripapillary atrophy, and disc hemorrhage. The quality of results is affected by factors such as focus, exposure, media, and magnification, and effectiveness is facilitated by making simultaneous comparisons, Dr. Greenfield said.

Several quantitative imaging systems are also available for detection of change and may be valuable as complementary tools to disc photography, he added. These systems offer greater reproducibility, increased sensitivity, and more robust identification of endpoints. But because they are relatively new, clinicians should regard them as complementary tools to optic disc photography when assessing glaucomatous progression rather than a replacement. Confidence limits are needed, based on disease stage, Dr. Greenfield explained, while software algorithms must be refined. In addition, these systems must be validated in prospective trials.

Both clinical judgment, based on numerous factors, and computer-assisted decision-making are required to assess progression, according to George A. "Jack" Cioffi, MD, Devers Eye Institute, Portland, OR. He is chief medical officer, senior vice president, and Chenoweth chair of ophthalmology at the institute. Technologies used to evaluate the visual field may generate either trend analysis or event analysis, and both are useful for the management of glaucoma patients. Trend analysis measures the rate of change of the visual field and the statistical significance of that rate. In event analysis, the first few visual fields are used as a baseline against which subsequent test results are compared to determine whether change has occurred.

Other factors used to estimate progression include the patient's age and life expectancy, the stage of disease, the progression rate and measurement technique, the risk of future progression, the aggressiveness of therapy, and the definition of visual disability.

To answer the question of whether a patient is getting worse, physicians must begin using computer-assisted decision making in addition to their clinical judgment, Dr. Cioffi said.

"This is the mode of the future and will let us get to the next step, which a way to plot progression over time, not just change," he said.

Jeffrey Liebmann, MD, introduced progression profiles, which are used to identify at-risk patients. Components of the profile include establishing an adequate baseline through data on optic nerve structure, visual function, IOP, and, when possible, old medical records that may contain invaluable prior structure and function information, said Dr. Liebmann, who is clinical professor of ophthalmology, New York University School of Medicine, and director, glaucoma services, Manhattan Eye, Ear, and Throat Hospital, New York.

The next step in the profile is staging the diseases, using structure and function data to classify it as mild, moderate, or severe glaucoma. An individual risk profile is then developed based on ocular and nonocular risk factors and consideration of life expectancy to account for cumulative risk over time. Dr. Liebmann emphasized that this risk profile changes over time and should be reevaluated periodically to get a more accurate picture of disease velocity for the specific patient. Once these steps have been taken, the profiling process is ongoing through regular evaluation of structure and function to detect progression.

Robert N. Weinreb, MD, distinguished professor of ophthalmology and director of the Hamilton Glaucoma Center, University of California, San Diego, School of Medicine, La Jolla, suggested that progression profiling be thought of as a cube, adding a layer to the profiling method Dr. Liebmann discussed to illustrate the complexity of progression management.

He cited a number of causes of retinal ganglion cell death but noted that elevated IOP is currently the only modifiable factor that can be treated.

"IOP may not be the whole story because we need to consider it along with perfusion, microcirculation, and the role of ischemia and hypoxia," Dr. Weinreb said. "Other factors, including excessive glutamate stimulation, other factors within the retina, and aberrant immunity all need to be considered as well."

While the pathology of glaucoma has been studied extensively at the retina and the optic nerve, recent evidence shows that degenerative changes also occur in the brain, said Neeru Gupta, MD, PhD, FRSC, DABO. Studies conducted several years ago demonstrated that lateral geniculate nucleus (LGN) atrophy occurs in primate glaucoma, as does LGN neuron shrinkage and death. More recently, it was shown that similar changes occur in humans. In a 2006 study, Dr. Gupta and colleagues found that in the presence of 50% visual field loss, degenerative changes were observed in major vision centers in the brain.

Further study of this pathway of progression may lead to improved methods of detecting or monitoring progression and managing patients with glaucoma, said Dr. Gupta, associate professor, ophthalmology and vision sciences, laboratory medicine and pathobiology, University of Toronto.

"If we are focusing our treatments on the eye and we understand that there are major changes going on all the way to the vision pathways into the brain, one might consider that anything we could do to boost the entire system would be of value," she said. "Furthermore, let's not forget that the source of major support to the eye is in fact the brain, which sends very important neurotrophic signals and growth factors and nutrients back to the eye to make sure it continues to function. The next time each of you looks at an optic nerve in practice, I would like you to consider the changes that are likely going on beyond the optic nerve head and that this likely represents the tip of the iceberg."

This continuing medical education activity was jointly sponsored by the New York Eye and Ear Infirmary and cme², a wholly owned subsidiary of Advanstar Communications Inc., publisher of Ophthalmology Times, and was supported through an unrestricted educational grant from Allergan.