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The prevalence of primary angle closure glaucoma in European derived populations: a systematic review
  1. Alexander C Day1,2,
  2. Gianluca Baio3,
  3. Gus Gazzard2,
  4. Catey Bunce1,2,4,
  5. Augusto Azuara-Blanco5,
  6. Beatriz Munoz6,
  7. David S Friedman6,
  8. Paul J Foster1,2
  1. 1Department of Genetics and Epidemiology, UCL Institute of Ophthalmology, London, UK
  2. 2NIHR Biomedical Research Centre for Ophthalmology, Moorfields Eye Hospital, London, UK
  3. 3Department of Statistical Science, University College London, UK
  4. 4The London School of Hygiene and Tropical Medicine, UK
  5. 5Health Services Research Unit, University of Aberdeen, UK
  6. 6Dana Center for Preventive Ophthalmology, Wilmer Eye Institute, Johns Hopkins University, Baltimore, USA
  1. Correspondence to Dr Alexander C Day, UCL Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK; alex.day{at}ucl.ac.uk

Abstract

Aim To estimate the prevalence of primary angle closure glaucoma (PACG) in European derived populations.

Method Systematic review and modelling of PACG prevalence data from population studies. PACG was defined according to the ISGEO definition requiring structural and/or functional evidence of glaucomatous optic neuropathy. Prevalence estimates were applied to the 2010 United Nations projected population figures to estimate case numbers.

Results The prevalence of PACG in those 40 years or more is 0.4% (95% CI 0.3% to 0.5%). Age-specific prevalence values are 0.02% (CI 0.00 to 0.08) for those 40–49 years, 0.60% (0.27 to 1.00) for those 50–59 years, 0.20% (0.06 to 0.42) for those 60–69 years and 0.94% (0.63 to 1.35) for those 70 years and older. Three-quarters of all cases occur in female subjects (3.25 female to 1 male; CI 1.76 to 5.94).

Conclusion This analysis provides a current evidence-based estimate of PACG prevalence in European derived populations and suggests there are 130 000 people in the UK, 1.60 million people in Europe and 581 000 people in the USA with PACG today. Accounting for ageing population structures, cases are predicted to increase by 19% in the UK, 9% in Europe and 18% in the USA within the next decade. PACG is more common than previously thought, and all primary glaucoma cases should be considered to be PACG until the anterior chamber angle is shown to be open on gonioscopy.

  • Angle closure glaucoma prevalence
  • Europe
  • iris
  • angle
  • anterior chamber
  • cornea
  • glaucoma
  • ciliary body
  • physiology
  • intraocular pressure
  • imaging
  • diagnostic tests/investigation
  • anatomy
  • treatment lasers
  • clinical trial
  • treatment surgery
  • epidemiology
  • treatment medical
  • field of vision
  • optic nerve
  • public health
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Introduction

Glaucoma is the leading cause of irreversible blindness worldwide.1 Data from East Asia show that while primary angle closure glaucoma (PACG) accounts for a quarter of all primary glaucoma cases compared with three-quarters for primary open angle glaucoma (POAG), it is more severe and the numbers of those blind from each are almost equal.1 Primary angle closure results from a combination of predisposing anterior segment anatomy and unfavourable physiological behaviour. It constitutes a spectrum ranging from those with anatomical risk: occludable angles (primary angle closure suspect, PACS), to primary angle closure (PAC) where there is evidence of trabecular meshwork damage/dysfunction (typically raised intraocular pressure (IOP) or peripheral anterior synechiae), to primary angle closure glaucoma (PACG) where there is additionally structural and/or functional evidence of glaucomatous optic neuropathy.2

The current understanding of angle closure disease (PAC and PACG) is based largely on studies from East Asia3–5 with little published data from European derived populations. Interpretation of population studies reporting the prevalence of PACG is complicated by great variation in diagnostic case definitions used, and without appropriate anterior chamber angle assessment PACG cases may be easily mistaken for POAG. Previous estimates for PACG in European derived populations range from 0.1%6 to 0.25%.1

As a result of the uncertainty surrounding the prevalence of PACG in European derived populations, we have carried out a detailed review of all population studies reporting prevalence values in European derived populations to determine the limits of available data, to estimate an overall prevalence of PACG consistent with the International Society for Geographical & Epidemiological Ophthalmology (ISGEO) definition requiring structural and/or functional evidence of glaucomatous optic neuropathy2 ,7 and to model future case numbers based on current population projections.

Methods

A literature review was performed using a systematic multi-staged approach to identify all studies with data on angle closure disease prevalence in European derived populations. PubMed was searched for all studies with ‘glaucoma’ and ‘prevalence’ as title words or medical subject headings (MeSH) from 1 January 1948 onwards. No language search limits were used. A final search was made on 5 September 2011. All abstracts were reviewed independently by two authors (ACD and AAB); population-based studies reporting on glaucoma prevalence conducted in European derived populations were identified and articles retrieved. Only studies reporting PACG prevalence data were included for this analysis. The searches were additionally cross-checked using the references from retrieved articles.

Population studies reporting PACG prevalence data were then assessed independently by two authors (ACD and GG) to determine their agreement with the following desirable criteria, all of which had to be met for inclusion for the current analysis: (a) Caucasian or predominantly Caucasian population, (b) random sampling of participants with (c) ≥70% examination rate of the eligible population sample; (d) PACG case definitions compatible with the current ISGEO definition2 ,7 using the uniform definition of glaucoma based on structural and/or functional evidence of glaucomatous optic neuropathy by (e) visual field testing and (f) optic disc evaluation by an ophthalmologist in the presence of an occludable anterior chamber angle determined by (g) gonioscopy. Prevalence study quality criteria were based on those suggested by Boyle in the evaluation of prevalence studies, and are more stringent than those used previously used.1 ,8 Figure 1 shows the flow path by which prevalence studies were identified.

Figure 1

Details of data sources for prevalence modelling.

PACG prevalence modelling was performed using an evidence synthesis framework.9 We considered a multi-level structure for the parameters (figure 2). At the first level, we considered parameters describing age-specific (40–49, 50–59, 60–69, 70+ years old) prevalence from studies reporting these data to estimate the prevalence for each age group. Second-level evidence was used to inform each age group parameter accounting for the relative weight estimated by the population age range sampled in each study. By assuming a common probabilistic structure based on random effect meta-analysis modelling, the information conveyed by each study was used to derive an estimation for each age-specific prevalence and an overall prevalence value for those 40 years old or more. The latter was based on population profile data from the 2010 revision of the UN World Populations Prospects database10 and was derived from the weighted sum of the age-specific values accounting for variability in the age-specific prevalence.

Figure 2

Flowchart showing identification method of studies for analysis.

Expected PACG case numbers were calculated using the age-specific prevalence values applied to the UN age-specific predicted population data from the medium variant of the UN World Populations Prospects database10 for UK, Europe and USA to calculate case numbers. As European derived populations are the predominant population group in the UK, Europe and the USA, no modelling was performed to account for immigration.

Results

Eighteen population studies reporting angle closure disease prevalence rates in European derived populations were identified (see table 1 and supplementary table 1, figure 1). Seven of these met all the inclusion criteria and were used to calculate the best evidence PACG prevalence estimates11–18 (Friedman et al, unpublished work, 2011) (table 1). Age-specific prevalence values (in addition to overall PACG prevalence values) were given by only two studies.11 ,12 Gender-specific data were available from four studies, with 58% (Friedman et al, unpublished work), 80%12, 85%11 and 100%16 PACG cases being in female subjects, resulting in an overall female to male ratio of 3.25:1 (95% CI 1.76 to 5.94).

Table 1

Details of the seven population studies included for analysis

PACG prevalence modelling using data from the seven population studies meeting the inclusion criteria showed age-specific prevalence of 0.02% (CI 0.00 to 0.08) for those 40–49 years old, 0.60% (0.27 to 1.00) for those 50–59 years old, 0.20% (0.06 to 0.42) for those 60–69 and 0.94% (0.63 to 1.35) for those 70 years old or above. The overall prevalence of PACG in those 40 years old or more is estimated to be 0.4% (95% CI 0.3% to 0.5%) in European derived populations (see figure 3).

Figure 3

Prevalence of primary angle closure glaucoma (PACG) in European derived populations (% population).

The estimated case numbers for PACG in European derived populations based on UN population projections for those 40 years old or more are shown in table 2 for UK, Europe and USA as calculated using the age-specific prevalence data. The relative increase in case numbers compared with those in 2010 due to predicted population structure change is shown in table 2.

Table 2

Estimated population with PACG (thousands) by region (95% CI)

Discussion

Of those over 40 years old in European derived populations, 0.4% are estimated to have PACG. Three-quarters of cases occur in female subjects. Our analysis suggests that PACG is between almost two and four times more common than previous estimates1 ,6 and there are 1.60 million people in Europe, 581 000 people in the USA and 130 000 people in the UK with PACG today. Accounting for the ageing population structure in these areas, cases are predicted to increase by 19% in the UK, 9% in Europe and 18% in the USA within the next decade. Our estimate of PACG prevalence is higher than previous estimates of 0.1%6 and 0.25%.1 The reasons for this are multifactorial. First, the accepted definition of PACG has changed considerably, data from new population studies are now available (Friedman et al, unpublished work)14 ,16 and also the analysis methods used to derive overall prevalence values differ.

Interpretation of PACG prevalence values from population studies is complicated by the inconsistent case definitions used (see table 1 and supplementary table 1) with some studies diagnosing PACG based only on a narrow anterior chamber angle with raised IOP19–21 (ie, PAC).2 In 2002, Foster et al proposed a standardised definition for PACG requiring structural and/or functional evidence of glaucomatous optic neuropathy in the presence of an ‘occludable’ angle with evidence of previous trabecular meshwork obstruction by peripheral iris (eg, raised IOP or peripheral anterior synechiae (PAS)).2 They defined an occludable angle as ≥270° of posterior trabecular meshwork not seen on gonioscopy in keeping with previous population studies.22 Thomas et al used a definition requiring ≥180° of irido-trabecular contact (ITC) for their studies in India.23 Later analysis by Foster et al showed the original 270° ITC definition to be too stringent as it excluded half of all individuals who had angle closure (seen by the presence of PAS) and glaucomatous optic neuropathy from being defined as PACG.24 The original description for occludable angle by Becker and Shaffer is believed to be the most inclusive definition7 with angle closure ‘probable’, and ‘possible’ with anterior chamber widths of 10° and 20° (grades 1 and 2), respectively.25 This variability in the gonioscopic definitions of an occludable angle is highlighted by comparison of the Egna-Neumarkt study11 where a Shaffer grade 0 was required for PACG diagnosis, whereas in the Ponza12 study, a Shaffer grade 2 or less was required. Clearly this will influence disease prevalence. Unpublished data from the Salisbury Eye Study show that using the ≥270° ITC definition, cases numbers are more than halved compared with when the ≥180° ITC definition is used (Friedman et al, unpublished work).14 While a revised consensus definition for an occludable angle has not been published, 180° or more of ITC has been proposed7 and is now the accepted clinical and research definition.26 Additionally, the advent of anterior segment OCT imaging suggests that gonioscopy does not detect all cases with ITC.27 We also found marked variability in the exact detail given for PACG definitions with PAS being described as part of the definition only in the Egna-Neumarkt11 ,18 and Salisbury Eye Evaluation Glaucoma Studies,14 and is assumed to have been part of the Wroclaw16 study based on their POAG definition. Furthermore, a raised IOP is only listed as a part requirement of a PACG definition in the Egna-Neumarkt,11 ,18 Ponza12 and Wroclaw16 studies. Ultimately, we used a pragmatic approach to identify studies with PACG definitions similar to the current ISGEO definition and included studies where the authors believed trabecular meshwork obstruction by peripheral iris to be the cause of the glaucoma. There were no studies with PACG definitions identical to the current ISGEO definition (although the Wroclaw16 study was closest), presumably as there are no prevalence studies that have been published following the ISGEO definition. The criteria for performing gonioscopy differed between studies, with gonioscopy typically only being performed once glaucoma was suspected,11 ,13–15 ,18 while others additionally performed gonioscopy if there was a shallow anterior chamber found on slit lamp or Van-Herrick grading.12 ,16 ,28 This may influence the identification of PACG cases.

Although there are no data comparing POAG and PACG disease severity in European populations, data from East Asia suggest that the risk of serious vision loss is considerably higher in PACG.5 As treatments including peripheral iridotomy and lens extraction can effectively arrest disease progression,29 ,30 there should be greater emphasis on accurate gonioscopy to discriminate between PACG and POAG when suspects are referred for glaucoma phenotyping. Following from this, we suggest that all primary glaucoma cases should be considered to be PACG until the anterior chamber angle is shown to be open on gonioscopy.

Our analysis has several limitations. The primary limitation being a consequence of the heterogeneity in PACG definitions and methods of anterior chamber angle assessment used as discussed. It is possible in our literature search that we missed prevalence studies that were not PubMed listed and we attempted to correct for this by reviewing the reference lists of all the prevalence studies we identified. In our model, we estimated the age-specific prevalence for 60–69 years old to be lower than that for those 50–59 or 70+ years old. This is surprising as PACG prevalence, like POAG, is believed to increase with age.1 This dip in the age-specific prevalence is also seen in the Ponza study,12 implicating this as a possible cause. However, a sensitivity analysis shows that even if there were no dip in observed prevalence in the Ponza study, it would still be present in our estimated age-specific prevalence values. We agree that it is likely that our 60–69-year age-specific prevalence is an underestimation, presumably due to the small number of studies contributing to the analysis. However, it is also possible that this finding is real and could be explained by different pathophysiological mechanisms that predominate at different ages, or that there may be increased cataract surgery rates in this age group leading to a cohort effect. Another limitation is that none of the PACG population studies from which we drew data enrolled all eligible participants and thus there is potential for response bias. Angle closure disease is more common in female subjects, who have longer life expectancy than male subjects, and our model did not account for this potentially underestimating case numbers. We also did not account for different PACG prevalence in ethnic minority populations. Again, this is likely to underestimate case numbers as PACG prevalence is higher in people of Asian and East Asian descent compared with European descent.1 In the USA especially, ethnic groups other than Caucasians form a large part of the whole population. In the Salisbury14 and Baltimore17 eye studies, 77% and 55% subjects respectively were Caucasian with the remainder being of African-American descent; the other studies did not report on the ethnicity of their populations. Finally, we assumed that the true PACG prevalence will not vary for any reason except population dynamics. This is unlikely to be the case as an analysis of UK hospital episode statistics showed the incidence of PACG appeared to be decreasing after reaching a peak in the late 1990s. The decline was attributed to increasing rates of phacoemulsification.31 More recent hospital episode statistics data show the decrease in PACG cases previously reported has reversed, with higher case numbers now than ever before and also that the incidence of acute angle closure in the UK appears to have halved in the past decade.32 These findings may in part be explained by increased physician awareness and increasing rates of phacoemulsification and laser peripheral iridotomy.

This analysis provides a current evidence-based estimate of PACG prevalence in European derived populations. PACG is more common than previously thought, and all primary glaucoma cases should be considered to be PACG until the anterior chamber angle is shown to be open on gonioscopy.

References

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Supplementary materials

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    This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.

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Footnotes

  • An additional table is published online only. To view this file please visit the journal online (http://bjo.bmj.com).

  • Funding Funding for this project was provided by The RD Crusaders Charitable Trust (via Fight for Sight, London; grant reference 1956). Dr Day and Professor Foster acknowledge a proportion of their financial support from the Department of Health through the award made by the National Institute for Health Research to Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology for a Specialist Biomedical Research Centre for Ophthalmology. Dr Baio is partly funded by the Department of Health through the award made by the National Institute for Health Research to UCL. The Health Services Research Unit, University of Aberdeen, UK, is core funded by the Chief Scientist Office of the Scottish government Health Directorates (AAB). The views expressed in this manuscript are those of the authors and not necessarily those of the Department for Health.

  • Competing interests None.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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