Ординатура / Офтальмология / Английские материалы / Mechanisms of the Glaucomas_Shields, Tombran-Tink, Barnstable_2008

PREVALENCE OF OAG

Disease Prevalence

Disease prevalence is defined as the number of current cases of a given disease per stated number of individuals in a population. It can be thought of as a snapshot of all the individuals with the disease of interest at a particular moment in time. Factors that affect disease prevalence include (i) how the presence or absence of disease is defined, (ii) the incidence of the disease (the number of new cases of disease per the population at risk over a given time interval), and (iii) the duration of the disease or the length of time individuals survive with the disease.

Defining Glaucoma

When assessing the incidence and prevalence of a given disease, it is important to first define the disease of interest. Traditionally, glaucoma was thought of as a disease of elevated intraocular pressure (IOP) (except for the normal-tension variant), and before 1996, investigators used a now-outdated case definition requiring an elevated IOP, along with the presence of visual field defects and abnormalities of the optic nerve or retinal nerve fiber layer. However, since studies in the mid-1990s demonstrated that IOP was an unacceptably poor predictor of glaucoma (4), elevated IOP has become thought of as a strong risk factor associated with glaucoma but no longer a requirement for the diagnosis.

The current definition of primary open-angle glaucoma (POAG), first promulgated by the American Academy of Ophthalmology (AAO) in 1996, is “a multifactorial optic neuropathy” with “a characteristic acquired loss of optic nerve fibers” (5). The definitive characteristics of glaucoma are based on visual field abnormalities, noted on achromatic automated perimetry or the appearance of the optic nerve or retinal nerve fiber layer. Early or mild glaucoma is characterized by optic-nerve abnormalities with normal visual fields. Thus, perimetric abnormalities also are no longer part of the case definition of glaucoma. Moderate glaucoma is defined as visual field abnormalities in one hemifield, not within 5° of fixation, whereas severe glaucoma involves visual field abnormalities in both hemifields or loss within 5° of fixation (5). Because many of the epidemiologic studies in the literature before 1996 required an elevated IOP or a visual-field defect for a glaucoma diagnosis, these studies underestimated the prevalence of the disease as it is currently defined. This should be kept in mind when comparing the prevalence estimates reported in the population-based studies discussed in this chapter.

Methods of Assessing the Prevalence of Open-Angle Glaucoma

The most widely accepted method of assessing disease prevalence is by using crosssectional surveys. These studies identify individuals with the disease of interest in a well-defined population at the specific time in which the survey is conducted. Large population-based, cross-sectional studies allow investigators to study the overall disease prevalence as well as the disease prevalence of subgroups of individuals within the community based on demographic profile or exposure status. While such studies can provide a wealth of information about the disease of interest, cross-sectional studies

have limitations. First, since these studies are conducted in a specific community, the prevalence rate generated may not represent that of other communities or the population as a whole. Second, these studies identify the presence or absence of disease among individuals at only one point of time; individuals without the condition are not followed longitudinally to determine whether they go on to develop the disease of interest.

Another possible method of determining the prevalence of a given disease is by using large healthcare claims databases. An advantage of using nationally representative claims databases is that investigators can assess the prevalence of disease throughout the USA, not simply in one specific community. Some of these databases, such as the National Long-Term Care Survey, follow individuals prospectively over time, allowing researchers to determine individuals in the cohort who go on to develop the disease of interest (6). A major limitation with using claims data is that it captures only those patients who enter the healthcare system, overlooking those without access to care. Claims data are also limited by investigators’ inability to verify that the data are accurate—that is, that persons submitting the claims have appropriately identified and coded patients with and without the disease of interest. As such, population-based survey studies remain the gold standard for defining disease prevalence.

Published Estimates Of Open-Angle Glaucoma

Beginning in the late 1970s, several large cross-sectional population-based studies determined the prevalence of various ocular conditions, including glaucoma. In the USA, these studies include the Baltimore Eye Survey (Baltimore, MD) (7), the Beaver Dam Eye Survey (Beaver Dam, WI) (8), the Framingham Eye Study (Framingham, MA) (9), the Proyecto Vision Evaluation Research (Nogales and Tuscon, AZ) (10), and the Los Angeles Latino Eye Study (LALES) (Los Angeles, CA) (11). Elsewhere, such studies include the Rotterdam Study (Rotterdam, the Netherlands) (12), the Melbourne Visual Impairment Project (Melbourne, Victoria, Australia) (13), the Blue Mountains Eye Study (Sydney, New South Wales, Australia) (14), the Barbados Eye Study (Barbados, West Indies) (15), the Kongwa Eye Project (Tanzania) (16), and a large Japanese study (17). Table 1 shows the number of participants enrolled and the demographic characteristics of the participants in many of these studies (1). Of note, the demographic profiles of the cohorts varied considerably from one study to another. As age, race, and possibly sex are risk factors associated with glaucoma, these variables contribute to some of the differences in prevalence rates reported among the studies.

Also of note, because no universally accepted epidemiologic definition of OAG exists, these studies used different criteria to classify patients as having OAG (see Table 2). Figure 1 shows the results of an analysis by Wolffs and colleagues in which different diagnostic criteria from various large population-based studies were applied to the participants enrolled in the Rotterdam Study (18). The findings show how the use of different criteria can dramatically affect prevalence estimates, thus underscoring the need for an internationally agreed-upon set of criteria for future population-based studies (18).

The overall estimates of OAG prevalence in the population-based studies range from 0.8 (Rotterdam) to 7% (Barbados) (12,15). The POAG prevalence estimates for the studies conducted in the USA range from 1.97 (Proyecto VER) to 4.74% (LALES) (10,11). When principal investigators from many of these studies pooled their data to

Table 1

Demographic Characteristics of individuals in Many of the Large Population-Based Studies (from Reference (1))

determine summary estimates, the overall prevalence of OAG for US adults aged 40 years and older was 1.86% (1).

In addition to the large population-based studies, numerous smaller observational studies have assessed OAG prevalence in different communities. Rudnicka and colleagues recently performed a meta-analysis of all published reports of OAG prevalence from 1973 to 2004, which included 46 studies conducted within and outside of the USA (19). Using a Bayesian approach, the investigators examined simultaneously the relationships between OAG prevalence and age, race, sex, and whether each survey included IOP or visual-field testing in the OAG case definition. In all, they found 2509 cases of OAG in an overall sample of 103,567 persons (2.4%) (19).

EFFECT OF AGE

Each of the large cross-sectional studies found that the prevalences of OAG rose with increasing age (1,7–17). Studies using Medicare claims data support the findings from the population-based studies that OAG prevalence increases with age (20). The increased OAG prevalence with older age is seen in men and women of all racial groups

(1) (see Table 3). The Bayesian meta-analysis showed OAG prevalence to increase exponentially with increasing age for each racial group (19) (see Fig. 2). This study also showed that while the prevalence of OAG was higher in blacks than in other racial

Table 2

Differences in Criteria Used to Classify Participants as Having Open Angle Glaucoma (OAG) in Many of the Large Population-Based Studies (from Reference (18))

Fig. 1. Differences in open-angle glaucoma (OAG) prevalence estimates for individuals in the Rotterdam Study resulting from using definitions of OAG from other population-based studies (from reference (18)).

Table 3

Prevalence of Glaucoma by Age, Gender and Race (from Reference 1)

Fig. 2. Increasing open-angle glaucoma (OAG) prevalence with age for all racial groups (from reference (19)).

groups at all ages, the increase in prevalence of OAG with age was steeper for whites than for blacks or Asians. For blacks and Asians, the odds of being diagnosed with OAG increases approximately 60% per decade, whereas for whites, the odds double per decade (19). It is important to note, however, that the population-based studies may underestimate OAG prevalence for the oldest age groups (>80 years) because of the small sample size of these groups. In contrast, Lee and colleagues have shown that following patients longitudinally, by using healthcare claims data, generates higher prevalence estimates for this oldest segment of the population (6).

EFFECT OF RACE

When assessing the impact of race on prevalence estimates, it should be remembered that for most studies, race is a self-reported variable. Furthermore, the number and types of races listed in population-based surveys vary from one survey to another, and this ultimately affects prevalence estimates. For example, in the Barbados Eye Study, the rate of glaucoma among non-US blacks was considerably higher than that among US blacks (15). When some studies combine these groups and others do not, the result can be a significant difference in disease estimates among studies (21). Using singlenucleotide polymorphisms obtained from blood samples, investigators are now starting to quantify the percentage of African and European ancestry of study participants (22). Girkin and colleagues (Personal communication, December 2006) are identifying whether self-reported race correlates well with study participants’ genetic profile. Data from such investigations will be useful for gauging the accuracy of self-reported race in previously conducted large population-based studies. These points must all be kept in mind when comparing the various glaucoma prevalence estimates reported according to race.

Whites

Three major population-based studies generated OAG prevalence rates for a cohort of predominantly white participants. The prevalence of OAG was 2.1% in the Beaver Dam Eye Survey (8) and 1.4% in the Framingham Eye Study (9). In the Baltimore Eye Survey, the prevalence of definite OAG was 1.1% and of definite or probable OAG was 1.4% (7). Pooling data from these studies along with the other population-based surveys involving persons of predominantly European-derived ancestry (Blue Mountains Eye Study, Rotterdam Study, and Melbourne VIP), the Eye Disease Prevalence Research Group found an OAG prevalence of 1.7% among whites aged 40 and older (1).

The Bayesian meta-analysis identified 21 observational studies assessing prevalence rates of OAG in whites, with a pooled OAG prevalence among these cohorts was 2.1% (19) (see Fig. 3). As most of these studies were conducted in Europe, however, this pooled prevalence may not reflect the OAG prevalence among US whites.

Blacks

The Baltimore Eye Survey was the largest US population-based, cross-sectional study to enroll blacks with OAG. Of the 5308 participants with OAG, 45% were black. The prevalence of definite OAG among blacks in this study was 4.2% while that for definite or probable OAG was 4.7% (7). According to logistic regression analyses, the prevalence of OAG in blacks was nearly three times that in whites (OR = 2.82) (7). Moreover, the magnitude of the difference in prevalence between blacks and whites increased with age. For participants aged 40–49, the rate of glaucoma was 0.92% for whites compared with 1.23% for blacks. However, the rate of OAG in white participants aged 80 or older was 2.2% compared with 11.3% among blacks in the same age group (7).

By using data from the 10 studies with black participants, the Bayesian metaanalysis found a pooled OAG prevalence of 4.23% for blacks (19). Figure 3 shows

Fig. 3. Meta-analysis of prevalence of open-angle glaucoma (OAG) stratified by racial group (from reference (19)).

the prevalence rates for each of the 10 individual studies included in this pooled prevalence estimate for blacks, as well as pooled prevalence estimates for other races (19). However, nine of the ten studies examined in the meta-analysis were conducted outside the USA (in Africa or the West Indies) and only one study (the Baltimore Eye Survey) included blacks residing in the USA.

Ostermann and colleagues (20) determined rates of glaucoma prevalence by using Medicare claims data linked to the National Long-Term Care Survey, a longitudinal study of 21,644 Americans aged 65 and older followed from 1991 through 1999. They found that the rate of POAG in 1991 was 7.5% in blacks, compared with 4.7% in whites while in 1999 the rates were 20.2 and 13.9%. The POAG prevalence ratio of blacks to whites was 1.6 in 1991 and 1.5 in 1999 (20). The joint prevalence of glaucoma and diabetic retinopathy was also higher in blacks than whites. For suspected glaucoma and other forms of manifest glaucoma, prevalence estimates throughout the study period did not differ between races (20).

All of these studies show that glaucoma is more prevalent among blacks than whites. The differences in OAG prevalence ratios between blacks and whites, which vary from approximately 1.5 to 1 up to 4 to 1, may be due, in part, to differences in study design. Unlike the Baltimore Eye Survey, which used specific criteria to clarify study participants as having POAG, Ostermann and colleagues (20) determined prevalence estimates on the basis of clinicians’ diagnostic criteria. Furthermore, because the ages of the study samples differed and older age is an independent risk factor for glaucoma, this variable also may have influenced the disparate prevalence rates for the two groups. Finally, the study by Ostermann and coworkers assessed glaucoma prevalence among patients over time, whereas the other studies evaluated individuals at only one point of time.

Latinos

Latinos are the fastest growing minority group in the USA. Presently, they constitute 12.5% of the US population, and census estimates predict that 25% of the US population will be of Latino or Hispanic origin by the year 2050 (11). Thus, the need to understand how glaucoma affects this segment of the population is becoming increasingly important.

Two large population-based, cross-sectional studies were designed to study the prevalence of glaucoma in Latinos. LALES studied OAG rates in Latinos, mostly of Mexican ancestry, residing in California. In this cohort of 6357 Latinos aged 40 or older, the prevalence of OAG was 4.7% (11). The Proyecto VER identified glaucoma prevalence rates among Latinos residing in Nogales and Tuscon, AZ. Of the 4773 Latinos aged 40 or older enrolled in this study, most of whom were of Mexican ancestry, the prevalence rate of POAG was 2% (10).

As both of these studies evaluated OAG in Latinos, primarily of Mexican ancestry, one can not infer that Latinos of Puerto Rican, Cuban, or Central American ancestry have similar prevalence rates of disease. Differences in OAG estimates between LALES and Proyecto VER may be due to actual differences between OAG rates among Latinos in these two communities. However, it may also be attributable to differences in study design, including the case definitions used or the inclusion of other forms of OAG in LALES but not in Proyecto VER.

Asians

The only large population-based study to report OAG prevalence for individuals of Asian descent was conducted outside the USA. A study of 8126 individuals in Japan

by Shoise and colleagues (17) found the prevalence of OAG to be 0.58% and of lowtension glaucoma to be 2.04%. The Bayesian meta-analysis, which pooled data from 14 small observational studies, generated a pooled OAG prevalence estimate of 1.41% among Asians (see Fig. 3) (19). However, of note, only one of the smaller studies included in the meta-analysis was conducted in the USA and that study noted only one case of OAG among 1686 individuals—considerably lower than the pooled estimate (19). Additional studies are warranted to obtain OAG rates for Asian Americans.

ESTIMATING THE NUMBERS OF INDIVIDUALS

IN THE USA WITH GLAUCOMA

By using the pooled prevalence data from the population-based studies, along with data from the 2000 US census, researchers have estimated that 2.2 million US citizens have OAG (23). As the population ages, the number is expected to increase by 50%, to 3.4 million, by 2020 (23). Another study, by Quigley and Vitale (24), that used statistical modeling to predict OAG prevalence rates estimated that 2.47 million US citizens had OAG in 2000. However, of note, if investigators were to use the AAO’s current criteria for case definition, the estimated number of persons in the USA with OAG could conceivably be as high as 15 million (7).

PREVALENCE OF BLINDNESS DUE TO GLAUCOMA

Quigley (25) estimated that 6.7 million people worldwide had bilateral blindness due to glaucoma in 2000, making glaucoma the second leading cause of blindness in the world. The World Health Organization reported that in 2002, 12% of blindness worldwide was attributable to glaucoma (26). Recently, the Eye Diseases Prevalence Research Group pooled data from many of the major population-based, cross-sectional studies to determine summary prevalence estimates of blindness and low vision in the USA. Using a definition of blindness as a best-corrected visual acuity (BCVA) of 20/200, or worse, in the better-seeing eye, this group found that glaucoma was the third most common cause of blindness among whites (6.4% of blindness attributable to glaucoma), behind macular degeneration and cataract (23). In blacks, it was the second leading cause of blindness (26% of blindness attributable to glaucoma), behind cataract (23). In Latinos, glaucoma was the leading cause of blindness (with 28.6% of blindness resulting from glaucoma) (see Fig. 4) (23). It is important to note that this pooled study included individuals considered to be blind due to glaucoma on the basis of BCVA only. By using data from a predominantly white cohort collected over a 34-year period in Olmstead, MN, in which blindness was based on visual acuity and visual field loss, researchers estimated that 19% of persons with glaucoma progressed to blindness (27). Tielsch and colleagues (28) found that the prevalence of bilateral blindness due to glaucoma (defined as BCVA of 20/200 or worse) was 5 and 14% among white and black nursing-homer patients, respectively.

Considering the findings of some studies that a higher percentage of blacks than whites experience blindness as a result of glaucoma, Ostermann and colleagues (20) performed additional analyses using claims data to try to explain the differences by race in the prevalence of blindness from OAG. They found that, on average, blacks