Evidence supports pressure-dependency of most glaucoma damage

Chicago-While epidemiologic studies indicate that only one-third of glaucoma damage is attributable to an excessive IOP over the normal distribution, the good news is that, nevertheless, much of the remainder is also pressure-dependent and, therefore, preventable.

That was the core message of the Robert N. Shaffer Glaucoma Lecture delivered by Paul F. Palmberg, MD, PhD, professor of ophthalmology at the Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, during the Prevent Blindness America Glaucoma Symposium at the American Academy of Ophthalmology. He spoke on the topic "How much of glaucoma damage is pressure-dependent?"

Dr. Palmberg pointed out that epidemiologic studies overall found only a weak relationship between IOP and glaucomatous damage. For example, in the 1966 study by Graham and Hollows that screened 4,000 persons in the United Kingdom, only one in 10 with a statistically elevated IOP had glaucoma. One-third of those with glaucoma had an IOP in the normal range. Nevertheless, there was only a single patient with glaucoma in the lower half of the pressure distribution of the whole sample, suggesting that lower normal pressures might protect against whatever else is responsible for glaucoma damage. Similarly, the Baltimore Eye Survey found a fairly steep dose-response relationship between IOP and the risk of visual field damage in the population, with an extremely low prevalence of glaucoma among persons with low IOP.

Lower IOP targets

Dr. Palmberg credited Paul A. Chandler, MD, for first advancing the concept that it is valuable to seek lower IOP targets in some patients, especially those with advanced glaucoma. In a landmark paper published in the American Journal of Ophthalmology in 1960, Dr. Chandler reported cases with long-term outcomes in which he had observed that eyes with damage to both poles of the disc usually required an IOP below the normal average to be stable, eyes with cupping confined to one pole of the optic disc usually did well with an IOP in the mid to upper normal range, and most eyes with a normal disc tolerated ocular hypertension for years without damage. Dr. Chandler's colleague, W. Morton Grant, reported a similar outcome study in 1982 on a series of eyes followed for 10 to 20 years.

By contrast, other studies that looked at glaucoma outcomes in patients in whom the strategy had been to maintain the IOP in the presumably safe upper normal range showed higher rates of progression. For example, Hart and Becker reported in 1982 that 73% of patients with manifest glaucoma experienced visual field loss over 10 years at an average IOP of 18 mm Hg.

Other information subsequently accumulated to support seeking lower pressures in patients with glaucoma damage severe enough to warrant surgery. In 1989, while helping to craft the AAO's preferred practice pattern for primary open-angle glaucoma, Dr. Palmberg performed a meta-analysis of glaucoma surgery outcome studies that suggested patients achieving an IOP in the low normal range were much less likely to experience progression than their counterparts with IOPs in the upper range of normal. At that time Palmberg coined the term "target pressure" to focus attention on patient-specific goals.

Aggressive intervention

More recently, the results from the large, prospective, multicenter, National Eye Institute (NEI)-sponsored, randomized clinical trials have helped to establish appropriate target pressures that are quite beneficial for patients with advanced glaucoma, normal-tension glaucoma, and even those with early damage.

"It is a good thing that the NEI and others provided the evidence to validate glaucoma treatment, because otherwise patients and health-care funding agencies might have lost confidence in what we do for a living. In 1987, a very annoying person named David Eddy had pointed out to health-care funding agencies that we had very little information about the natural history of glaucoma or evidence for the benefit of treatment. It was part of the push to have evidence-based guidance to justify treatments in all of medicine. Fortunately, during the following decade, large prospective studies have helped to clarify the role of IOP in glaucoma development and progression and provided evidence-based guidance for treatment of various forms of the condition," he said.