Do Ethnicity and Gender Influence Glaucoma Prevalence?

Your patient's background may put them more at risk

By Hana Takusagawa, MD, and Steven Mansberger, MD, MPH

Is race important when examining your glaucoma patients? Many studies suggest that the prevalence of glaucoma varies significantly according to ethnicity, race and gender. However, the definition of ethnicity and distinction between ethnicity and race are often unclear. Furthermore, race may be a surrogate for other factors related to glaucoma such as central corneal thickness, cup-to-disc ratio and intraocular pressure. This article seeks to review the current literature, review treatment variations when they exist, and suggest alternative factors that may be used in evaluating risk.

Primary Open Angle Glaucoma

Does the prevalence of OAG vary with ethnicity?

Primary open angle glaucoma (OAG) is the most common form of glaucoma in the US, with an estimated prevalence of approximately 1.86% in adults 40 years and older, affecting approximately 2.2 million Americans.¹ According to the literature, primary open angle glaucoma varies significantly according to race and ethnicity. Prevalence estimates in white patients over the age of 40 in the United States is 1.69%.¹ According to the Baltimore Eye Study, OAG is three times more prevalent among African Americans in the United States than among Caucasians.² Likewise, studies of black West Indian populations in St. Lucia and Barbados show a prevalence of 8.8% and 6.6%, respectively.^3,4

Two studies show a higher prevalence of OAG in the Latino population in the United States. Proyecto VER, a population-based study in Arizona, found a prevalence of 1.97% in Latino adults over the age of 40.⁵ The Los Angeles Latino Eye Study (LALES), also a population-based study (with a large percentage of Latinos of Mexican ancestry) shows a prevalence of 4.89%.^6,7

Similar to blacks and Latinos, studies in other ethnic groups show a higher prevalence of glaucoma. Recent analysis of insurance data shows a prevalence of OAG in Asian Americans similar to that of Latinos and between that of Caucasian and African Americans.⁸ Subgroup analyses of the different Asian-American ethnicities in this study show an especially elevated prevalence in those of Japanese ancestry, with a particularly high rate of normal tension glaucoma. This agrees with the Tajima Eye Study, a population-based study in Japan that found an OAG prevalence of 3.9% of the population; 92% of those open angle patients had normal eye pressures.⁹ American Indian/Alaskan Native populations also show a large percentage of normal-tension glaucoma with a 6.2% prevalence of open angle glaucoma, 100% of which had normal eye pressures.¹⁰

Does it vary with gender?

Studies of gender differences present conflicting evidence. The Framingham eye study showed twice the prevalence in men vs women. In Sweden, OAG was more frequent among women. Many other studies have shown no difference.

Should OAG be treated differently based on race/ethnicity?

It is tempting to treat differently based on race and ethnicity. Indeed, the Advanced Glaucoma Intervention Study (AGIS) showed significantly different outcomes in subgroup analysis of African-American and Caucasian-American patients.¹¹ African-American patients had improved long-term visual function outcomes with a sequence of ALT–trabeculectomy– trabeculectomy. Caucasian patients had better outcomes with the trabeculectomy–ALT–trabeculectomy treatment sequence.¹¹ In addition, the Ocular Hypertension Treatment Study (OHTS) showed that black race was a risk factor for conversion from ocular hypertension to open angle glaucoma in a univariate analysis.¹² However, in a multivariate analysis, race was no longer a risk factor in the development of glaucoma if corneal thickness and cup-to-disc ratio were included in a multivariate regression analysis of risk factors. This suggests that corneal thickness and cup-to-disc ratio may present a better means of evaluating risk factors than race.

The Socioeconomic Question

While the prevalence of glaucoma in African-Americans in the United States is three to four times that of Caucasian patients, African-Americans are six to 10 times more likely to go blind from glaucoma when compared to their Caucasian counterparts.¹³ In addition, the Baltimore Eye study found that African-Americans appeared to develop glaucoma 10 years earlier than their white counterparts.¹³ Is this due to inherent increased susceptibility or to socioeconomic factors? Some studies suggest that this difference may be related to poor clinic follow-up, insufficient treatment or late diagnosis.¹⁴ Population-based prevalence studies have found that as many as 80% of participants had previously undiagnosed glaucoma.

Closed Angle Glaucoma

Closed angle glaucoma is the second most common form of glaucoma worldwide, but the most likely cause of blindness from glaucoma. Closed angle glaucoma has several forms, including primary angle closure with pupillary block and chronic angle closure glaucoma. Of these, chronic angle closure (often a “creeping” angle closure) is by far more frequent. A particularly high rate of acute angle closure glaucoma is found in the Inuit population with a prevalence of 2.65% in the adult population over 40 having angle closure, and 17% over the age of 50 having occludable angles. In these studies, women were found to be four times more likely to have angle closure glaucoma than men.^15,16 In mainland China, in the Liwan Eye Study, a population-based study, the prevalence of anatomically narrow angles (but not closed angle glaucoma) has been reported as high as 10%.¹⁷ In this population, closed angle glaucoma appears to be more common than open angle glaucoma.

In the US, the prevalence of anatomically narrow angles in white Americans is estimated to be 2-6%, with only 0.2% of the population developing angle closure glaucoma.^18,19 Recent studies of Asian Americans have also found a high prevalence rate of narrow angles in Asian Americans when compared to their Caucasian, African, and Latino-American counterparts.⁸ In subgroup analyses by ethnicity, those with Vietnamese, Chinese, Indian, Korean, Filipino and Japanese backgrounds had a significantly elevated prevalence of closed angle glaucoma compared to the general US population. The prevalence of primary angle closure glaucoma in Latinos in the US appears to be similar to or less than that of the white population at 0.1%. It also appears to be uncommon in the African-American population.²⁰

A glaucomatous optic nerve from a Caucasion male. Rather than using race to evaluate glaucoma, looking at factors like nerve appearance, anterior segment examination and gonioscopy are far more effective.

This information highlights the difficulty of using race as a risk factor. Asians may have a higher rate of narrow angles, however “Asian” refers to a heterogeneous population. There are significant differences between those of Chinese background, who have a high prevalence of narrow angles and narrow angle glaucoma, and those of Japanese background, whose risk is similar to the Caucasian population in the US. Similar issues can be found in defining other races, such as African-Americans. Studies show the highest prevalence in West Indian blacks with a fourfold increase in comparison to blacks in South Africa. Overall, race may be a surrogate for other factors related to glaucoma such as CCT, cup-to-disc ratio, gonioscopic angle appearance and perhaps socioeconomic status.

Pigmentary Dispersion Glaucoma

Traditionally thought to be fairly uncommon, pigment dispersion syndrome can lead to elevated IOP in approximately 50% of those affected, as excess pigment clogs the trabecular meshwork. It was found in 2.45% of white patients undergoing glaucoma screening in one US study²¹ and is thought to affect Caucasian patients much more frequently than black or Asians. Though the prevalence of pigment dispersion is equal between men and women, glaucoma is more likely to affect men more commonly than women throughout most ethnicities. Women who are affected have an onset of glaucoma 10 years later than their male counterparts. However, one study indicates that a subpopulation of black patients with pigment dispersion has a female preponderance, an older age of onset and hyperopic refraction.²² The reason for this gender difference in development of glaucoma is unknown.

Pseudoexfoliation Glaucoma

Also a secondary glaucoma, pseudoexfoliation was first found to have a high prevalence in Scandinavian countries. However, it is found in all populations to varying degrees. Prevalence by race and ethnicity appears to vary widely within and between regions. For example, in South Africa it is found more frequently among black patients than among white patients with glaucoma.

However, in a study based in Louisiana, it is much more common in white patients than black patients. Recently, a strong genetic association with polymorphisms of lysyl oxidase-like 1 gene (LOXL1) has been found.²³ Yet, while 92% of patients with pseudoexfoliation have this gene, 74% of the control population also has this gene, suggesting that other factors likely play a role.²⁴ One study found that environmental factors may play an important role in the formation of this syndrome, with increasing incidence at lower ambient temperatures, and higher sunlight levels as potential triggers from pseudoexfoliation.²⁵ No strong evidence suggested variation according to gender, though several recent studies point to a female predominance.²⁶

This suggests another difficulty of using race in relationship to glaucoma — risk factors may be associated with environmental factors separate from an inherent susceptibility to glaucoma.

Conclusions

Using race and ethnicity factors in glaucoma diagnosis and treatment is a tempting proposition, but it is one fraught with pitfalls. Perhaps the strongest correlation between race and glaucoma risk and treatment effectiveness appears in the study of primary open angle glaucoma. Here, it seems clear that African-American patients are more likely to develop OAG and more likely to become blind from the disease. However, few papers in the literature precisely define race and ethnicity, and such categories may be particularly problematic for ophthalmologists to apply in clinical practice. Furthermore, it is unclear if the differences observed between race/ethnicity and disease prevalence vary according to genetics, environment, socioeconomic status and cultural differences (including compliance/adherence to treatment regimens and access to care).

It is not clear how much each of these factors plays in the risk of developing glaucoma, and how a patient may respond if glaucoma does develop. For now, make sure to evaluate intraocular pressure, the optic disc, central corneal thickness and the angle with gonioscopy. Be sure to evaluate the anterior chamber to diagnose secondary glaucomas such as pseudoexfoliation and pigment dispersion. These have fewer pitfalls when compared to race.

One thing that is certain in patients across all racial and ethnic divides: many are not aware that they have glaucoma. OM

References

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	Hana L. Takusagawa M.D. is a glaucoma fellow at the Devers Eye Institute and the Casey Eye Institute in Portland, Oregon. After the completion of her fellowship, she will be staying as an Assistant Professor of Ophthalmology at Oregon Health Science University's Casey Eye Institute. Her email is takusaga@ohsu.edu.
	Steven L. Mansberger, M.D., M.P.H. is an Associate Scientist and Director of Glaucoma Services and Ophthalmic Clinical Trials for the Devers Eye Institute in Portland, Oregon. He also holds appointments at Oregon Health Science University (OHSU) as Clinical Associate Professor of Ophthalmology and Public Health and Preventive Medicine.