Primary angle closure glaucoma (PACG) is higher in Asians than Europeans and Africans, with over 80% of PACG worldwide in Asia. Previous estimates of PACG were based largely on early studies, mostly using inappropriate case definitions. Therefore, we did a systematic review and meta-analysis to estimate the prevalence of PACG in adult Asian populations and to quantify its association with age, gender, and region.
All primary reports of population-based studies that reported the prevalence of PACG in adult Asian populations were identified. PACG case definition was compatible with the ISGEO definition. Twenty-nine population-based studies were included. The overall pooled prevalence estimates were calculated using a random effect model, and ethnicity-, age- and gender-specific pooled prevalence estimates were also calculated.
The overall pooled prevalence of PACG in those of adult Asians was 0.75% (95% CI, 0.58, 0.96). Ethnicity-specific pooled prevalence estimates were 0.97% (0.22, 4.27) in Middle East group, 0.66% (0.23, 1.86) in South East Asia group, 0.46% (0.32, 0.64) in India group, 1.10% (0.85, 1.44) in China group, and 1.19% (0.35, 3.98) in Japan group, respectively. Age-specific prevalence was 0.21% (0.12, 0.37) for those 40–49 years, 0.54% (0.34, 0.85) for those 50–59 years, 1.26% (0.93, 1.71) for those 60–69 years, and 2.32% (1.74, 3.08) for those 70 years or above. The overall female to male ratio of the PACG prevalence was 1.51∶1 (95% CI 1.01, 2.28).
Citation: Cheng J-W, Zong Y, Zeng Y-Y, Wei R-L (2014) The Prevalence of Primary Angle Closure Glaucoma in Adult Asians: A Systematic Review and Meta-Analysis. PLoS ONE 9(7): e103222. https://doi.org/10.1371/journal.pone.0103222
Editor: Ted S. Acott, Casey Eye Institute, United States of America
Received: April 26, 2014; Accepted: June 25, 2014; Published: July 24, 2014
Copyright: © 2014 Cheng et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: The authors confirm that all data underlying the findings are fully available without restriction. All relevant data are within the paper and its Supporting Information files.
Funding: This work was supported by Shanghai Rising-Star Program (Grant No. 12QA1404600), Shanghai Municipal Natural Science Foundation (Grant No. 10ZR1439300), and National Natural Science Foundation of China (Grant No. 81000374 and 81170874). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
Glaucoma is considered as the leading cause of irreversible blindness worldwide, with Asians accounting for approximately half of the world's glaucoma cases . It also has been accepted that primary angle closure glaucoma (PACG) is higher in Asians than Europeans and Africans, with over 80% of those with PACG in Asia , . Because PACG appears to cause blindness more frequently than primary open angle glaucoma (POAG), it is an important public health issue.
The current understanding of PACG in Asian populations is based largely on previous studies –. Early studies using the definitions of glaucoma based on intraocular pressure (IOP) reported that the prevalence of PACG in adults was 0.34% in Japan , 1.49% in Mongolia , 1.37% in China , and 1.18% in India , respectively. However, the earlier definitions of glaucoma are no longer accepted , and the prevalence rates reported in these earlier studies may not be accurate and comparable .
The International Society of Geographical & Epidemiological Ophthalmology (ISGEO) definition has demonstrated the general accepted classification for the diagnosis of glaucoma in population-based prevalence surveys . However, the current understanding of PACG in Asians is based largely on studies using the earlier definitions of glaucoma, but not the ISGEO definition, which increasingly was seen as inadequate for both clinical and research purposes , , . Recently, many population-based surveys of glaucoma in Asians using the ISGEO definition have been conducted. Because of the uncertainty surrounding the prevalence of PACG, this systematic review was to summarize the available population-based studies reporting prevalence values in Asians, to estimate an overall prevalence of PACG consistent with the ISGEO definition requiring structural and/or functional evidence of glaucomatous optic neuropathy.
Materials and Methods
This meta-analysis was performed according to a predetermined protocol, and the methods used conformed to the Meta-analysis of Observational Studies in Epidemiology and the relevant aspects of the PRISMA statement , .
We used three methods to identify publications that reported the prevalence of PACG among Asian populations. First, we conducted a systematic search of the PubMed and EMBASE electronic databases from each database's inception date to February 10, 2014. Broad MeSH terms and keywords were used combining terms related to epidemiology (including MeSH search using exp prevalence*, and exp epidemiology*, and keyword search using words prevalence, epidemiology, and incidence), terms related to disease (including MeSH search using exp glaucoma*, and keyword search using words glaucoma), and terms related to population (including MeSH search using exp Asia*, and keyword search using words Asia, and Asian). Second, we hand-searched the reference lists of the relevant reviews, such as Rudnicka 2006 , Quigley 2006 , Wong 2006 , Zhou 2007 , and Cheng 2013 . Third, we consulted the reference lists of included articles to find additional studies.
Published studies were included if they met the following inclusion criteria: (i) population-based, cross-sectional survey studies, with either random or consecutive sampling; (ii) adult Asian populations, customarily aged 40 years and older; (iii) a examination rate of the eligible population sample not less than 50%; (iv) PACG case definitions compatible with the current ISGEO definition based on structural and/or functional evidence of glaucomatous optic neuropathy in the presence of an occludable anterior chamber angle.
To determine study eligibility, three independent researchers screened the titles and abstracts of all search results, and all citations were classified into one of two categories: (i) relevant; (ii) irrelevant. The full articles of relevant citations were retrieved for further review to evaluate whether they met the inclusion criteria or not. Only eligible trials were assessed for methodological quality. Disagreements were resolved by consensus in both phases.
The following detailed information was extracted into a customized proforma: (i) study information (study name, publication year, citation, and study type), (ii) basic study data (geographical region, country of survey area, conditions in survey area, data collection year, sample size, and sociodemographic characteristics), (iii) quality-related data and outcome measures data (target population, sampling design, completeness of data/response rate, data collection, prevalence, definition and identification procedures for outcomes). Three reviewers independently carried out the data extraction, and inconsistencies were resolved by discussion with another independent reviewer.
Risk of Bias Assessment
Two reviewers independently assessed the risk of bias for each included study, using a checklist developed from an existing tool assessing risk of bias in prevalence studies. The tool includes 10 items that assess measurement bias, selection bias, and bias related to the analysis (all rated as either high or low risk) and an overall assessment of risk of bias rated as either low, moderate, or high risk , . To adapt to the needs of this meta-analysis, we also modified item 9 as “Were the screening process and assessing methods for the parameter of interest appropriate?” , .
Agreement was measured using kappa value as recommended by the Cochrane Handbook for Systematic Reviews of Interventions , and disagreement was resolved finally by discussion. Overall agreement between the reviewers was 93% with a kappa value of 0.76, indicating excellent agreement.
All statistical analyses were performed using Comprehensive Meta-Analysis software version 2.0 (Biostat, Englewood Cliffs, New Jersey) (http://www.meta-analysis.com). The primary outcome for each study was the prevalence proportion, calculated as the ratio of the number of individuals with PACG to the total number of study participants. The I2 statistic was used to determine heterogeneity across studies, which quantify heterogeneity irrespective of the number of studies , . The estimate and its 95% confidence intervals (CI) of overall proportion was calculated using the random effects model where heterogeneity was found , otherwise, the fixed effects model was used .
Ethnicity-specific pooled prevalence estimates of PACG were calculated, using a random effect model, which included the dominant ethnic group of five regions in Asia: Middle East, South East Asia, India, China, and Japan . Age- and gender-specific pooled prevalence estimates of PACG were also calculated. A random-effect meta-regression model was built with ethnicity, age, and gender.
In addition, to attempt to control for potential methodologic heterogeneity, a random-effect regression model was also used to evaluate sources of variability in the overall pooled-prevalence estimate, such as urbanicity, the definition of occludable angle and the individual risk-of-bias items.
Figure 1 shows the flow chart of the selection process used to identify relevant studies. We reviewed the full text of 117 articles from 1997 studies identified from the literature search, and 88 articles were excluded (Appendix S1). Twenty-nine population studies met all the inclusion criteria and were used to calculate the best evidence PACG prevalence estimates in adult Asian populations (Table 1) –. Seven studies (24%) were conducted in China, 5 (17%) in India, 3 (10%) in Singapore, 2 (7%) in Japan, Korea, and Nepal, and 1 (3%) in Bangladesh, Iran, Mongolia, Myanmar, Oman, Qatar, Thailand, and Sri Lanka. Fifteen studies (52%) were undertaken in rural, 6 (21%) in urban, and 8 (28%) in mixed populations. The age ranges of the studied populations were 30 years and over, with the majority of studies (n = 20, 69%) being 40 years and over, and the male portion of the populations ranged from 36% to 64%. Twenty-five studies (86%) used ISGEO definition for the diagnosis of PACG.
PACG: primary angle closure glaucoma
Risk of Bias
Overall, 22 studies (76%) were rated as having a low risk of bias, 7 (24%) were rated as having a moderate risk of bias (Table 2). High risk-of-bias ratings were most common for item I (national representativeness/target population), item IV (non-response bias), item VI (case definition), and item VII (study instrument).
The prevalence of PACG reported in the included studies varied from 0.13% to 2.50% in adult Asian populations (Figure 2). The heterogeneity in the prevalence of PACG was statistically significant and substantial in considerable. The overall random-effects estimate of the prevalence of PACG in adult Asian populations was 0.75% (95% CI, 0.58, 0.96).
Ethnicity-specific pooled prevalence estimates of PACG of five Asian regions are shown in Figure 3. The pooled prevalence estimates of PACG were 0.97% (95% CI, 0.22, 4.27) in Middle East group, 0.66% (0.23, 1.86) in South East Asia group, 0.46% (0.32, 0.64) in India group, 1.10% (0.85, 1.44) in China group, and 1.19% (0.35, 3.98) in Japan group, respectively. The meta-regression analyses showed there was a strong association of prevalence with ethnic group (β = 0.27, P = 0.009).
Fifteen studies reported age-specific prevalence of PACG, and twenty-two studies reported gender-specific prevalence. The age-specific prevalence was 0.21% (95% CI, 0.12, 0.37) for those 40–49 years old, 0.54% (0.34, 0.85) for those 50–59 years old, 1.26% (0.93, 1.71) for those 60–69 years old, and 2.32% (1.74, 3.08) for those 70 years old or above (Figure 3). Meta-regression analysis showed a high prevalence rate was strongly associated with an older age of sample (β = 0.74, P<0.0001). The pooled prevalence was 0.63% (0.49, 0.82) for male and 0.91% (0.68, 1.21) for female (Figure 3). Meta-regression analyses showed a strong association between a high prevalence rate and a higher proportion of female gender (β = 0.41, P = 0.047), and the overall female to male ratio of the PACG prevalence was 1.51∶1 (95% CI 1.01, 2.28).
The meta-regression analyses showed there was no association of the prevalence rate with urbanicity (β = −0.17, P = 0.524). The prevalence of PACG was also not associated with the definition of occludable angle (β = −0.05, P = 0.717). For risk-of-bias items, the prevalence rate was not associated with a high risk of bias for item I (β = 0.48, P = 0.217), item IV (β = −0.40, P = 0.391), item VI (β = 0.06, P = 0.882), and item VII (β = 0.77, P = 0.112).
This comprehensive systematic review was conducted to investigate the prevalence of PACG in Asian, and to understand the reasons of estimate variability. The findings showed that for those of adult Asian populations, 0.75% were estimated to have PACG. This systematic review also quantified the variability in the prevalence of PACG for age, gender and ethnic group. The rate of PACG prevalence increased with age, approximately double per decade. PACG prevalence in women was approximately 1.5 times that in men. There was a strong variability of PACG prevalence rates by ethnic group.
It has been established that the prevalence of glaucoma varies significantly by region , , , . On the basis of the findings from this systematic review, there was also significant ethnic variation in the prevalence of PACG among five Asian regions. The highest prevalence rates of PACG were reported in Japan (1.19%) and China (1.10%), followed by Middle East (0.97%), South East Asia (0.66%), and India (0.46%). A recent systematic review found that the prevalence of PACG in those 40 years or more in European derived populations is 0.4% (95% CI 0.3% to 0.5%) . Therefore, the prevalence of PACG in Asians, especially in East Asians and South East Asians, is higher than those in Europeans. However, the findings should be interpreted with caution, especially for the Japan, Middle East and South East Asia groups, because of the very wide confidence interval of prevalence rates, and the significantly large heterogeneity across included studies.
The pooled prevalence of PACG in five Asian ethnic group from the present review was inconsistent with the results reported in the previous reviews , . In the previous reviews , , the prevalence of PACG was over-diagnosed in South East Asia, India, and China regions, and under-diagnosed in Middle East and Japan regions. Interpretation of the over- and under-diagnosis of PACG prevalence values is complicated by the inappropriate case definitions used in some studies diagnosing PACG, especially those based only on a narrow anterior chamber angle with raised IOP .
An appropriate case definition is the keystone of epidemiological research, and the ISGEO definition has commonly been accepted since it was published . A consensus definition of an “occludable” angle in which the posterior (usually pigmented) trabecular meshwork is seen for less than 90°of angle circumference has come into common usage to indicate the anatomical predisposition to angle closure , , . However, the definition of an “occludable” angle excluded around half of all participants who have primary peripheral anterior synechiae (PAS) . Although a slightly more liberal threshold, 180 degrees of iridotrabecular contact (ITC), was used in many population studies, it is still likely to exclude many people who have primary PAS. Therefore, the most widely used epidemiological definition of an “occludable” angle, 180–270 degrees of ITC, is too stringent. The traditional view that primary angle closure becomes a significant possibility in the iridotrabecular angle of 20 degrees probably represents the most inclusive of approaches , . In addition, gonioscopy using visible light probably under-detects cases where ITC is occurring . Although the results of this present review showed no association between the prevalence of PACG and the definition of occludable angle, in future, the definition of an “occludable angle” used in epidemiological studies of glaucoma still should be reconsidered.
There are several limitations of this systematic review should be discussed. First, similar to most systematic reviews, a potential limitation is the publication bias. We attempted to avoid the potential for publication bias by conducting an extensive search. However, the studies published in languages other than English probably was missed. Second, available studies were from only 14 countries. Thus, more population-based studies should be required to estimates the whole prevalence in Asian populations. Third, the diagnostic criteria for glaucoma and occludable angle also differed among studies. Although no association between the prevalence and case definitions was found, the expanding definition of an ‘occludable’ angle will allow for better consideration of this possibility through research and clinical practice .
Nevertheless, this systematic review provides a current evidence-based estimate of PACG prevalence in Asian populations. In the past, the number of PACG worldwide probably was misestimated. PACG affects approximately 0.75% adult Asian populations, and the prevalence rates vary greatly by ethnic region. The findings of this present systematic review provide benefit to estimate the burden of PACG in Asia.
The excluded articles and the reason for exclusion.
Conceived and designed the experiments: JWC YZ YYZ RLW. Performed the experiments: JWC YZ YYZ RLW. Analyzed the data: JWC YZ YYZ. Contributed reagents/materials/analysis tools: JWC YZ YYZ. Contributed to the writing of the manuscript: JWC YZ YYZ RLW.
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