glaucoma
Patients at Risk
Myriad factors influence the way we study the development of glaucoma — and treat it.
DANIEL K. ROBERTS, O.D., M.S.

Primary open-angle glaucoma (POAG) is an important public health problem in the United States. It's characterized by a chronic, usually progressive, optic neuropathy in adults, which produces an acquired atrophy of the optic nerve. This is associated with loss of retinal ganglion cells and their axons. Patients with POAG have open anterior chamber angles. There is no other known reason for the glaucomatous optic nerve changes. Intra-ocular pressure (IOP) is often elevated, but may also be normal. Here, we'll review the incidence and prevalence of POAG, as well as risk factors.

Epidemiological evaluations

An important issue in the study of POAG concerns the accuracy and consistency of its diagnosis because it is not necessarily easy to establish the presence of glaucomatous cupping of the optic nerve head. From a clinical perspective, suspicious "cupping" may actually represent normal, physiologic variation, and seemingly normal optic nerves may actually be abnormal. Also contributing to diagnostic difficulty is the fact that the results of automated threshold perimetry, a mainstay of testing, can be notoriously unreliable. Thus far, attempts to solve this problem with new diagnostic testing strategies and methods have not produced the "magic bullet." Certainly additional testing modalities can be helpful, but none is always a reliable indicator to determine the presence or absence of POAG.

Another problem with epidemiologic investigations of POAG is that elevated IOP is not considered as important for the diagnosis of disease as it once was. Evolving and changing diagnostic criteria for POAG can impact the validity of certain disease estimates and comparability among studies. In addition to over- and under-estimation errors, non-homogenous study samples may lead to greater difficulty in identifying factors with true association with POAG.

The prevalence of POAG in the U.S. begins to increase around age 40 in most racial and ethnic groups.

Prevalence

POAG is a worldwide disease with no known population completely unaffected by it. It's estimated that more than 60 million people worldwide are afflicted with the disease. Recently, the Eye Diseases Prevalence Research Group (2004) calculated age-specific POAG prevalence estimates for white, black, and Hispanic persons in the United States based on a meta-analysis of population-based studies conducted in the United States, Australia and Europe. The data pooled from large individual studies supports information relative to race and ethnicity and helped project prevalence figures for the year 2020. (See charts on page 43.)

In whites, for example, about 1% of women age 55-59 have POAG. For those 65-69 years old, prevalence increases to 1.58% and to 3.12% for patients between 75-79 years old. For women, men and different ethnic groups, POAG prevalence increases with age. In most age groups, African Americans consistently have the highest POAG prevalence; whites the lowest. For example, for men age 65-69, the prevalence is 1.64% in whites, 2.07% in Hispanics and 7.24% in African Americans.

Applying age, race, and gender prevalence estimates to 2000 U.S. Census Bureau data, The Eye Diseases Prevalence Research Group estimates POAG currently affects about 2.22 million people. With the aging of the U.S. population, this figure is expected to soar, becoming an even greater public health concern. The number of people in the United States with POAG is projected to increase to 3.36 million by 2020.

Incidence

The incidence of POAG has not been studied as well as its prevalence. In large part, this is due to greater difficulty in collecting relevant data. Whereas prevalence indicates the number of existing cases of disease in a specified population at a given time, incidence rates indicate the number of new cases developing in a specified population during a particular interval of time. Incidence is the percentage of an at-risk population that develops the disease. Alternatively, incidence is commonly reported as the number of new cases per 100,000 people at risk for the disease. Reliable incidence data, therefore, require good population data prior to development of disease and adequate follow-up data to accurately determine if and when the disease developed. 

A long-term, prospective investigation is the ideal study design to determine the incidence of a disease. Because this is difficult and expensive, retrospective studies are often substituted. These may suffer from unavailable and incomplete testing data, the application of highly variable and outdated diagnostic data, and changing disease definitions.

The impact of technology

With newly available technology and treatment options, it's not unusual to find a change in the incidence rate of a disease shortly after the introduction of the new technology. Evaluating newly-diagnosed POAG residents between 1965 and 1980, the authors of a recent study calculated an age- and gender-adjusted annual incidence of 14.5 new cases per 100,000 people, predominantly white. Prior to 1979, the average annual incidence was 12.3 new cases per 100,000, but during the last two years of the study (1979-1980), the incidence was 27.7 new cases per 100,000. The authors propose the dramatic difference in incidence before and after 1979 is most likely due to the advent of new medical therapy, namely beta-blockers, which became available to area practitioners in the last two years of the study.

When a new, promising medical therapy becomes available, it should not be surprising that practitioners may look more diligently for a disease. They may even be more willing to make a particular diagnosis after a new therapy becomes available.

Along with the age- and gender-adjusted incidence estimate for POAG, researchers found POAG incidence rates increased significantly with age. Estimated incidence in the fourth decade of life was 1.6 cases per 100,000 vs. 94.3 cases in the eighth decade. The authors did not find a significant difference in the incidence of POAG relative to gender.

Not much information exists on incidence relative to race and ethnicity. The Barbados Eye Study, conducted from 1988 to 1992, consisted of a simple, random sample of Barbadian-born citizens, between the ages of 40 and 84. In the initial sample, 93% of 4,631 subjects reported their race as black. The observed four-year incidence of POAG was 1.2% in 40-49 year-olds, 1.5% in 50-59 year-olds, 3.2% in 60-69 year-olds and 4.2% in those over 74. Obviously, these four-year estimates are higher than annual incidence rates due to the longer period of study.

Risk factors

Several important risk factors for POAG have been identified (see table below). Age is a well-established risk factor for POAG, with risk increasing significantly after age 40. Although elevated IOP is clearly a risk factor for the disease, it is not a requirement. Contemporary investigation of glaucoma reflects this sentiment, with elevated IOP not required for its diagnosis. Rather, POAG diagnosis depends on demonstrable cupping and visual field loss.

A greater awareness of corneal thickness' role in the accurate measurement of IOP further diminishes the requirement for IOP elevation. Even with adjustment for the influence of corneal thickness, adjustments based on population data may be erroneous for individual patients.

African American race is an important and definitive risk factor for POAG. Depending on the age group, POAG prevalence may be six times higher in African Americans than in whites. In addition, POAG appears earlier and is likely to be more severe in African Americans than whites. Corneal thickness is more likely to be thinner in African Americans, a factor that may result in underestimation of the IOP in some individuals. This may account for some, but not all, of the variation between African Americans and whites relative to POAG. Hispanic and Latino ethnicity is also now considered a risk factor for POAG. These patients are at greater risk than whites, but lower than African Americans.

Family history is another important risk factor for POAG. Clearly, the genetics are complex and not easily unraveled, but POAG in a close relative is an important risk indicator. The Baltimore Eye Survey reported the relative risk of developing POAG is more than three times higher for those who have a sibling with POAG.

Although older age, elevated IOP, decreased central corneal thickness, a family history of glaucoma, and African-American or Hispanic/Latino ethnicity are generally the most recognized risk factors, a few other factors may also put patients at risk. Systemic hypertension and hypotension also appear to be risk factors for POAG. It's speculated that perfusion pressure within the microcirculation of the optic nerve, as well as its auto-regulation, may be a factor in disease development for some patients.

Diabetes is also a suspected risk factor for POAG. Although many patients with diabetes have glaucoma, some believe the relationship disappears if other variables are adequately controlled. Further study is necessary.

Myopia is another suspected risk factor. A two- to three-fold increase in risk for glaucoma has been reported in people with at least low amounts of myopia.

Management

Management goals for POAG include controlling IOP in order to stabilize the optic nerve and nerve fiber layer, which will help stabilize the visual field. The mainstay of treatment is topical medical therapy. Other options include laser, filtering or cyclodestructive surgery. Initial therapy depends on a number of patient-specific factors.

The amount of IOP reduction that will prevent further deterioration of the optic nerve will vary from person to person. There is no way to know exactly how much lowering will be required in a given patient. As a general rule, however, lower IOP by 20% relative to pretreatment levels. Generally, more aggressive IOP lowering is helpful when disease status is more severe. In all patients, continually assess the adequacy of therapy by evaluating the optic nerve, nerve fiber layer and visual field. Then, adjust target IOP based on this reassessment.

References will be furnished upon request.