The Association of Blood Pressure and Primary Open-Angle Glaucoma: A Meta-analysis


To conduct a systematic review and meta-analysis of the association between blood pressure levels and hypertension with primary open-angle glaucoma and intraocular pressure endpoints.


Systematic review with quantitative meta-analysis.


Studies were identified by searching the PubMed and EMBASE databases. Inverse-variance weighted random-effects models were used to summarize relative risks. Subgroup analyses and meta-regression were used to explore potential sources of heterogeneity across studies.


Sixty observational studies were included. The pooled relative risk for primary open-angle glaucoma comparing patients with hypertension to those without hypertension was 1.16 (95% CI = 1.05–1.28), with modest heterogeneity across studies ( I 2 34.5%). Virtually all studies reported a positive association between blood pressure and intraocular pressure (IOP). The pooled average increase in IOP associated with a 10 mm Hg increase in systolic blood pressure was 0.26 mm Hg (95% CI 0.23–0.28, I 2 30.7%), and the average increase associated with a 5 mm Hg increase in diastolic blood pressure was 0.17 mm Hg (95% CI 0.11–0.23, I 2 90.5%).


In this meta-analysis, hypertension was associated with increased intraocular pressure. The association between hypertension and primary open-angle glaucoma was stronger in cross-sectional compared with case-control and longitudinal studies. Our findings support a role of increased blood pressure in elevated intraocular pressure and possibly in the development of glaucoma.

Glaucoma is the leading cause of irreversible blindness, affecting more than 60 million people worldwide. The risk and prognosis of primary open-angle glaucoma (POAG), the most common type of glaucoma, is influenced by demographic factors such as age, race, and family history, and by several ocular parameters including myopic refractive error, optic disc shape, and corneal thickness. Increased intraocular pressure (IOP) is the most important modifiable risk factor for POAG, but there is substantial interest in identifying other potentially modifiable risk factors.

Systemic hypertension may contribute to increased IOP via overproduction or impaired outflow of aqueous humor. Some but not all population studies have found statistically significant positive associations of systolic blood pressure (SBP) and diastolic blood pressure (DBP) with IOP. Furthermore, the literature on the association between blood pressure (BP) and POAG is limited and inconsistent. Qualitative reviews have summarized the evidence on BP, IOP, and glaucoma, but these reviews did not conduct systematic searches of the literature to incorporate all relevant studies and did not produce quantitative estimates of the associations. In addition, most studies included in these reviews were published before 2005. The objective of this meta-analysis was thus to summarize and quantitatively synthesize available literature on the association of BP with IOP and POAG.

Materials and Methods

Search Strategy

Our systematic review and meta-analysis was conducted according to the Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines. To identify relevant studies, we searched MEDLINE and EMBASE for observational studies investigating the relation of BP or hypertension with POAG, IOP, or ocular hypertension (OHT), with no restrictions on language or publication date. The search period was through April 2013. Keywords included systolic blood pressure, diastolic blood pressure, blood pressure, hypertension, intraocular pressure, intraocular tension, eye pressure, eyeball pressure, eye internal pressure, intraorbital pressure, ocular pressure, ocular tension, intraocular hypertension, intraocular tension, and glaucoma. In addition, we manually reviewed the reference lists from relevant original research.

Study Selection

We aimed to identify all relevant observational studies that assessed the association of BP or hypertension with IOP, OHT, or POAG in general population settings. We applied the following exclusion criteria: (1) reviews, editorials, or letters; (2) case reports or case series; (3) studies not conducted in humans; (4) studies not conducted in adults; (5) studies conducted in population samples composed only of patients with established glaucoma or ocular hypertension at baseline; (6) studies not reporting glaucoma, IOP, or OHT outcomes; (7) studies not using BP or hypertension as exposure; (8) studies investigating mainly drug effects or metabolism; and (9) studies of populations with specific conditions (eg, pregnancy or eye surgery) that limit their generalizability to general population samples. Furthermore, since age is a strong risk factor for glaucoma and for hypertension development, we further excluded studies that did not adjust for age in the design or the analysis.

For studies that did not report POAG separately from other types of glaucoma, we used results for open-angle glaucoma or glaucoma as endpoints. For studies that reported both cross-sectional associations at baseline and prospective longitudinal associations, we included both associations separately by design. If more than 1 paper reported on the same association within a study population, we selected the publication with the largest sample size or the longest follow-up. Several studies reported estimates of measures of association without standard errors or any other estimates of statistical variability. These studies were included in the systematic review but were excluded from the quantitative meta-analysis.

Data Extraction and Quality Assessment

Two investigators (D.Z. and M.K.) independently reviewed all search results to identify eligible papers and abstracted data from selected articles, including study design, study population, age and sex distribution, sample size, study outcomes, duration of follow-up, exposure and outcome assessment, main results, and variables included in the adjusted model. Discrepancies between reviewers were solved by consensus. We assessed the risk of bias in studies using the methods described by Sanderson and associates and Viswanathan and associates. We examined the methods for selecting study participants, the criteria for defining exposures and outcomes, the risk of bias associated with different designs, the methods used to control for confounding, and potential conflicts of interest.

Statistical Analysis

The study endpoints were POAG, IOP, and OHT. We used as many endpoints as reported in each study and conducted separate meta-analyses for each endpoint ( Table ). For hypertension, we combined hazard ratios, odds ratios, and relative risks for POAG or OHT, comparing participants with vs those without hypertension, and average differences in IOP (in mm Hg) comparing participants with vs those without hypertension. For SBP and DBP, we combined hazard ratios, odds ratios, or relative risks for POAG or OHT associated with an increase of 10 mm Hg for SBP and of 5 mm Hg for DBP, and average differences in IOP (in mm Hg) associated with an increase of 10 mm Hg for SBP and of 5 mm Hg for DBP. These measures of association and their 95% confidence intervals (CIs) were abstracted or derived from published data. For studies reporting standardized regression coefficients, we used the standard deviations for BP and IOP reported for that population to recalculate unstandardized regression coefficients. Finally, for studies reporting measures of association based on log-transformed SBP or DBP, we calculated the measures of association based on 10 and 5 mm Hg increases in SBP or DBP, respectively, calculated from the population mean.


Characteristics of the Studies Included in the Meta-analysis of the Association Between Blood Pressure and Primary Open-Angle Glaucoma

First Author, Year Country Population Setting Sample Size Recruit (Follow-up) Year Exposure Outcome IOP Measure Mean Age/Range (y) Mean IOP (mm Hg) Prevalence of POAG/OHT (%)
Leske, 1983 USA Framingham Heart Study and Framingham Eye Study Community 2433 1975 HTN OHT GAT NA NA NA
David, 1987 Israel Participants from urban areas in southern Israel Health screening examination 2594 1984 HTN OHT GAT 40–79 15.0 NA
Wormald, 1994 UK African Caribbean immigrants living in London Community 873 1991 HTN Glaucoma NA >35 NA 3.5
Dielemans, 1995 Netherlands The Rotterdam Study Community 4187 1993 SBP, DBP IOP GAT 55–95 14.6 NA
Tielsch, 1995 USA The Baltimore Eye Survey Community 5308 1988 SBP, DBP, HTN POAG NA >40 NA 3%
Nomura, 1999 Japan Office workers and their family members Health screening examination 68 998 1997 SBP, DBP IOP NCT 20–79 11.8 NA
Bonomi, 2000 Italy The Egna-Neumarkt Study Community 4297 NA HTN POAG NA 40–89 NA 1.4
Quigley, 2001 USA Hispanics in Arizona Community 4774 1990 SBP, DBP, HTN OAG GAT >40 15.6 2
Nomura, 2002 Japan National Institute for Longevity Sciences–the Longitudinal Study of Aging program (NILS-LSA) Community 1317 1999 SBP, DBP IOP NCT 40–80 13.5 NA
Yoshida, 2003 Japan Participants from a general hospital Health screening examination 569 2000 SBP, DBP IOP NCT 29–79 12.9 NA
Mitchell, 2004 Australia The Blue Mountains Eye Study Community 3654 1994 HTN OAG GAT 66.2 NA 3
Bai, 2005 China Participants in rural province in China Community 1775 2003 HTN POAG PAT 50–91 NA NA
Chen, 2005 Taiwan Hospital-based healthy subjects Health screening examination 1271 2001 SBP, DBP IOP NCT 50.0 13.6 NA
Mitchell, 2005 Australia The Blue Mountains Eye Study Community 3302 1994 SBP, DBP IOP PAT 49–97 NA NA
Oh, 2005 South Korea Healthy visitors to health promotion center Health screening examination 943 2003 SBP IOP NCT 45.8 15.4 NA
Hulsman, 2007 Netherlands The Rotterdam Study Community 5317 1993 SBP, DBP OAG GAT 68.8 16.0 4
Vijaya, 2008 India The Chennai Glaucoma Study Community 3850 2004 HTN POAG GAT 54.8 15.2 3.5
Tan, 2009 Singapore The Singapore Malay Eye Study Community 3280 2006 SBP, DBP, HTN POAG GAT 58.7 NA 3.2
Wang, 2009 China The Beijing Eye Study Community 3222 2006 HTN POAG NCT 60.4 15.7 2.4
Chang, 2010 Taiwan University hospital Health screening examination 1044 2006 SBP, DBP IOP NCT 50.8 14.5 NA
Imai, 2010 Japan General hospital Health screening examination 14 003 2008 HTN OHT NCT 18–83 14.8 NA
Memarzadeh, 2010 USA Los Angeles Latino Eye Study Community 6130 2003 SBP, DBP OAG GAT 54.7 14.2 4.7
Park, 2010 South Korea Kyunggi Province Community 446 2008 SBP, DBP IOP NCT 41.6 12.4 NA
Graw, 2011 Germany KORA Eye Study Community 2593 1999 HTN Glaucoma NA 32–71 NA 1.5
Ishikawa, 2011 Japan Subjects attending community health screenings Health screening examination 710 2007 HTN POAG GAT >30 15.1 3.7
Topouzis, 2011 Greece Thessaloniki Eye Study Community 2261 1999 HTN POAG GAT 70.4 15.9 6
Goldacre, 2012 UK Analysis of the Oxford Record Linkage Study (ORLS) and English Linked Hospital Episode Statistics (LHES) Community 94 591 ORLS: 1963–1998 HTN Glaucoma NA 0–80+ NA 1.1
LHES: 1999–2010
Kim, 2012 South Korea Survey of local residents Community 1464 2006 HTN POAG GAT 63.7 13.5 3.8
Lee, 2012 South Korea Healthy Twin Study Community 3096 2005 SBP IOP NCT 37.8 13.7 NA
Sun, 2012 China Villagers Community 4956 NA HTN POAG PAT >40 14.0 0.7
Morgan, 1975 Canada Cases drawn from University of British Columbia, and from a private practitioner with a large glaucoma referral practice Hospital outpatient clinic 91 cases, 91 controls NA HTN POAG, OHT NA NA NA NA
Reynolds, 1977 USA Records from pathology clinic Hospital outpatient clinic 87 cases, 87 controls 1975 HTN OAG NA ≥18 NA NA
Wilson, 1987 USA Patients from General Eye Service of the Massachusetts Eye and Ear Infirmary Community 121 cases, 237 controls 1984 SBP, HTN POAG NA NA NA NA
Katz, 1988 USA Patients from Wilmer Institute, Johns Hopkins Hospital Hospital outpatient clinic 94 cases, 94 controls NA SBP, DBP, HTN Glaucoma GAT NA NA NA
Uhm, 1992 USA Patients from Kresge Eye Institute Hospital outpatient clinic 361 cases, 927 controls NA HTN POAG GAT 65.5 NA NA
Charliat, 1994 USA Patients from private practice and public hospitals Hospital outpatient clinic 175 cases, 175 controls 1994 HTN POAG GAT 65.7 16.9 NA
kaimbo, 2001 Congo Patients from an ophthalmologic clinic Hospital outpatient clinic 40 cases, 104 controls 1997 SBP, DBP, HTN OAG GAT 28–81 19.3 NA
Fan, 2004 China Patients from a hospital Hospital outpatient clinic 32 cases, 96 controls 2000 HTN POAG GAT 32–71 20.6 NA
Orzalesi, 2007 Italy Patients from outpatient clinic Hospital outpatient clinic 2879 cases, 973 controls NA HTN POAG GAT 67.2 16.2 NA
Mcleod, 1990 USA Baltimore Longitudinal Study of Aging Community 572 1966, 6 y follow-up SBP, DBP IOP ST 19–89 16.1 NA
Hennis, 2003 West Indies Barbados Eye Study Community 2996 1988, 4 y follow-up HTN IOP GAT 57.5 18.4 NA
Klein, 2005 USA Beaver Dam study Community 4926 1990, 5 y follow-up SBP, DBP IOP GAT 60.4 15.4 NA
Nakano, 2005 Japan Male aircraft crew members Community 2330 1985, 5 y follow-up SBP, DBP IOP GAT 35.9 13.8 NA
Wu, 2006 West Indies Barbados Eye Study Community 2298 1992, 9 y follow-up SBP, DBP IOP GAT 55.1 17.5 NA
Leske, 2008 West Indies Barbados Eye Study Community 3222 1992, 9 y follow-up SBP, DBP, HTN OAG NA 56.9 18.0 NA
Newman-Casey, 2011 USA InVision Data Mart database Community 2 182 315 2001, 6 y follow-up HTN OAG NA 54.5 NA Incidence: 2.5

DBP = diastolic blood pressure; GAT = Goldmann applanation tonometer; HTN = hypertension; IOP = intraocular pressure; NA = not available; NCT = noncontact tonometer; OAG = open-angle glaucoma; OHT = ocular hypertension; PAT = Perkins applanation tonometer; POAG = primary open-angle glaucoma; SBP = Systolic blood pressure; ST = Schiotz tonometer.

When several models for a given endpoint were reported in the same study, we selected the maximally adjusted model. For studies reporting results separately by subgroups (eg, men and women, hypertension with and without medication, hypertension only and with other diseases, or participants from different locations), we used each group as an independent result for the meta-analyses. For studies reporting both overall and subgroup results, we used overall estimates.

We used DerSimonian and Laird’s random-effects models to calculate summary relative risks across studies. Between-study heterogeneity was quantified using the I 2 statistic, which describes the proportion of total variation in study estimates attributable to heterogeneity. We also assessed the relative influence of each study by omitting 1 study at a time from the pooled analysis. Publication bias was evaluated using funnel plots and Egger’s tests. The funnel plots depict the distribution of the measures of association vs their standard errors. The null hypothesis of Egger’s test is that the regression of measures of association over their standard error has an intercept of zero. The rejection of the null hypothesis ( P < .05) suggests that the measures of association depend on the study sample size, which may reflect publication bias. We assessed heterogeneity of the association of hypertension or BP with study outcomes by study type (case-control, cross-sectional, longitudinal), location (Europe, America, Asia, others), and year of publication (<2000, ≥2000) using meta-regression with restricted maximum likelihood estimates of between-study variance. We did additional meta-regression by adjustment for IOP (Yes, No) and adjustment for central corneal thickness (Yes, No).

Studies presenting measures of association for BP in 3 or more categories or as continuous exposures were also combined using a random-effects dose-response meta-analysis. One study reporting the dose-response association between BP and POAG was excluded because of the small number of POAG cases in each BP interval. All statistical analyses were conducted with Stata version 12 (STATA Corp, College Station, Texas, USA).


Study Characteristics

We identified 60 studies (44 cross-sectional, 9 case-control, and 7 longitudinal cohort studies) that met our inclusion criteria ( Figure 1 , Supplementary Table 1 , available at ). Twenty-six studies were performed in Asia, 13 in the United States, 9 in Europe, 3 in the West Indies, 3 in Australia, 3 in Canada, 2 in the Middle East, and 1 in Congo. The prevalence of POAG in cross-sectional studies ranged from 0.7% to 9%. The number of studies that presented quantitative estimates and 95% CIs that could be incorporated in our meta-analysis was 29 for POAG (27 with estimates for hypertension, 10 for SBP, and 8 for DBP), 5 for OHT (4 with estimates for hypertension, 1 for SBP, and 1 for DBP), and 18 for IOP (3 for hypertension, 17 for SBP, and 14 for DBP).

Figure 1

Flow chart of study selection process for the meta-analysis of the association between blood pressure and primary open-angle glaucoma.

POAG, open-angle glaucoma, and glaucoma criteria differed across studies. To identify and define glaucoma cases, 9 studies considered characteristics of the optic disc, anterior chamber angle, optic nerve damage, or visual field changes; 14 studies also considered OHT as an additional criterion; 2 studies used self-reported glaucoma; 1 study used medical history records; and 1 study used ICD-9 codes from a medical database. Among the studies that assessed the association between BP and IOP, 5 measured IOP using a Goldmann applanation tonometer, while the rest used noncontact tonometers, Schiotz tonometers, or handheld tonometers. The average IOP of the study populations ranged from 11.5 to 16.1 mm Hg ( Table ). For studies reporting OHT as an outcome, 1 study defined OHT as IOP >20 mm Hg, 1 as IOP ≥21 mm Hg, and 3 as IOP >21 mm Hg. The studies also differed in their definition and ascertainment methods for hypertension ( Supplementary Table 2 , available at ) and in the covariates adjusted for ( Supplementary Table 3 , available at ).

Primary Open-Angle Glaucoma

The association between hypertension and POAG was heterogeneous across studies. Eighteen studies reported a positive association and 9 studies reported an inverse or null association. Seven studies adjusted for IOP and 2 studies adjusted for central corneal thickness (CCT) in their analysis. The pooled relative risk (RR) for POAG comparing participants with vs those without hypertension was 1.16 (95% CI 1.05–1.28), with modest across-study heterogeneity ( I 2 34.5%) ( Figure 2 ). The pooled RR was significant for cross-sectional studies (1.24, 95% CI 1.06–1.44), but it was smaller and not statistically significant for case-control (1.08, 95% CI 0.92–1.28) and longitudinal studies (1.05, 95% CI 0.69–1.59), although only 2 longitudinal studies contributed to the pooled estimates. The overall pooled RR in sensitivity analysis based on studies that defined POAG without using IOP as a diagnostic criterion was 1.14 (1.03–1.25, I 2 24.0%). In dose-response meta-analysis of studies that presented data using 3 or more categories of BP or that reported BP as a continuous exposure, the pooled RR for POAG associated with a 10 mm Hg increase in SBP was 1.01 (95% CI 1.00–1.03, I 2 26.1%) and the pooled RR associated with a 5 mm Hg increase in DBP was 1.02 (95% CI 0.99–1.04, I 2 25.9%) ( Figure 3 ).

Figure 2

Relative risks for primary open-angle glaucoma comparing patients with hypertension to those without hypertension. The size of the box representing the point estimate for each study in the forest plot is proportional to the contributing weight of that study estimate to the summary estimate. Horizontal lines represent 95% confidence intervals.

Figure 3

Relative risk for primary open-angle glaucoma with increasing levels of blood pressures in dose-response meta-analysis. Circle areas are inversely proportional to the variance of the log relative risks from studies using categorical systolic blood pressure or diastolic blood pressure intervals. Dashed lines correspond to studies that used systolic blood pressure or diastolic blood pressure as a continuous variable. The pooled linear risk trend (thick solid line) and its 95% confidence band (shaded region) were obtained using a random-effects dose-response meta-analysis. The individual studies were (first author, year): (1) Tan, 2009; (2) Kaimbo, 2001; (3) Memarzadeh, 2010; (4) Tielsch, 1995; (5) Hulsman, 2007; (6) Katz, 1988; (7) Quigley, 2001; (8) Dielemans, 1995; (9) Leske, 2008; (10) Wilson, 1987.

Intraocular Pressure

Virtually all studies reported a positive association or correlation between SBP, DBP, and IOP ( Figure 4 , Supplementary Table 4 , available at ). The pooled average increase in IOP associated with a 10 mm Hg increase in SBP was 0.26 mm Hg (95% CI 0.23–0.28, I 2 42.5%), and the average increase associated with a 5 mm Hg increase in DBP was 0.17 mm Hg (95% CI 0.11–0.23, I 2 91.2%), with similar results in cross-sectional compared to longitudinal studies. The pooled average difference in IOP comparing participants with vs those without hypertension was 0.33 mm Hg (95% CI 0.25–0.40, I 2 0%), although this estimate was based on only 3 studies ( Figure 5 ).

Figure 4

Increase in intraocular pressure associated with a 10 mm Hg increase in systolic blood pressure and a 5 mm Hg increase in diastolic blood pressure. The square represents the point estimate for each study. The area of each square is proportional to the inverse of the variance of the estimate. Horizontal lines represent 95% confidence intervals.

Jan 8, 2017 | Posted by in OPHTHALMOLOGY | Comments Off on The Association of Blood Pressure and Primary Open-Angle Glaucoma: A Meta-analysis

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