Michelle Py Chan

Global variations and time trends in the prevalence of primary open angle glaucoma (POAG): a systematic review and meta-analysis.

Systematic review of published population based surveys to examine the relationship between primary open angle glaucoma (POAG) prevalence and demographic factors. A literature search identified population-based studies with quantitative estimates of POAG prevalence (to October 2014). Multilevel binomial logistic regression of log-odds of POAG was used to examine the effect of age and gender among populations of different geographical and ethnic origins, adjusting for study design factors. Eighty-one studies were included (37 countries, 216 214 participants, 5266 POAG cases). Black populations showed highest POAG prevalence, with 5.2% (95% credible interval (CrI) 3.7%, 7.2%) at 60 years, rising to 12.2% (95% CrI 8.9% to 16.6%) at 80 years. Increase in POAG prevalence per decade of age was greatest among Hispanics (2.31, 95% CrI 2.12, 2.52) and White populations (1.99, 95% CrI 1.86, 2.12), and lowest in East and South Asians (1.48, 95% CrI 1.39, 1.57; 1.56, 95% CrI 1.31, 1.88, respectively). Men were more likely to have POAG than women (1.30, 95% CrI 1.22, 1.41). Older studies had lower POAG prevalence, which was related to the inclusion of intraocular pressure in the glaucoma definition. Studies with visual field data on all participants had a higher POAG prevalence than those with visual field data on a subset. Globally 57.5 million people (95% CI 46.4 to 73.1 million) were affected by POAG in 2015, rising to 65.5 million (95% CrI 52.8, 83.2 million) by 2020. This systematic review provides the most precise estimates of POAG prevalence and shows omitting routine visual field assessment in population surveys may have affected case ascertainment. Our findings will be useful to future studies and healthcare planning.

Systemic Medication and Intraocular Pressure in a British Population The EPIC-Norfolk Eye Study

Objective To determine the association between systemic medication use and intraocular pressure (IOP) in a population of older British men and women. Design Population-based, cross-sectional study. Participants We included 7093 participants from the European Prospective Investigation into Cancer–Norfolk Eye Study. Exclusion criteria were a history of glaucoma therapy (medical, laser, or surgical), IOP asymmetry between eyes of >5 mmHg, and missing data for any covariables. The mean age of participants was 68 years (range, 48–92) and 56% were women. Methods We measured IOP using the Ocular Response Analyzer. Three readings were taken per eye and the best signal value of the Goldmann-correlated IOP value considered. Participants were asked to bring all their medications and related documentation to the health examination, and these were recorded by the research nurse using an electronic case record form. The medication classes examined were angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, α-blockers, β-blockers, calcium channel blockers, diuretics, nitrates, statins, insulin, biguanides, sulfonylureas, aspirin, and other nonsteroidal anti-inflammatory drugs. We examined associations between medication use and IOP using multivariable linear regression models adjusted for age, sex, and body mass index. Models containing diabetic medication were further adjusted for glycosylated hemoglobin levels. Main Outcome Measures Mean IOP of the right and left eyes. Results Use of systemic β-blockers (−0.92 mmHg; 95% CI, −1.19, −0.65; P<0.001) and nitrates (−0.63 mmHg; 95% CI, −1.12, −0.14; P = 0.011) were independently associated with lower IOP. The observed associations between statin or aspirin use with IOP were no longer significant after adjustment for β-blocker use. Conclusions This is the first population-based study to demonstrate and quantify clinically significant differences in IOP among participants using systemic β-blockers or nitrates. Lower IOP observed in participants using statins or aspirin was explained by concurrent systemic β-blocker use. The study findings may have implications for the management of glaucoma patients with comorbidity, and may provide insight into the pathophysiologic processes underlying IOP.

The EPIC-Norfolk Eye Study: rationale, methods and a cross-sectional analysis of visual impairment in a population-based cohort

Objectives To summarise the methods of the European Prospective Investigation of Cancer (EPIC)-Norfolk Eye Study, and to present data on the prevalence of visual impairment and associations with visual impairment in the participants. Design A population-based cross-sectional study nested within an on-going prospective cohort study (EPIC). Setting East England population (the city of Norwich and its surrounding small towns and rural areas). Participants A total of 8623 participants aged 48–92 years attended the Eye Study and underwent assessment of visual acuity, autorefraction, biometry, tonometry, corneal biomechanical measures, scanning laser polarimetry, confocal scanning laser ophthalmoscopy, fundal photography and automated perimetry. Outcome measures Visual impairment was defined according to the WHO classification and the UK driving standard, and was based on presenting visual acuity. Summary measures of other ophthalmic measurements are also presented. Results The prevalence (95% CI) of WHO-defined moderate-to-severe visual impairment and blindness was 0.74% (0.55% to 0.92%). The prevalence (95% CI) of presenting visual acuity worse than the UK driving standard was 5.87% (5.38% to 6.37%). Older age was significantly associated with visual impairment or blindness (p<0.001). Presenting visual acuity worse than UK driving standard was associated with older age (p<0.001), female sex (p=0.005) and lower educational level (p=0.022). Conclusions The prevalence of blindness and visual impairment in this selected population was low. Visual impairment was more likely in older participants, women and those with a lower educational level.

Associations With Retinal Nerve Fiber Layer Measures in the EPIC-Norfolk Eye Study

PURPOSE To describe GDxVCC retinal nerve fiber layer (RNFL) measures and associations in a predominantly white British population. METHODS The EPIC-Norfolk Eye Study is nested within a large multicenter cohort study, the European Prospective Investigation of Cancer. RNFL measurements were taken using the GDxVCC. Generalized estimating equation models were used to assess associations of RNFL measures with age, sex, body mass index (BMI), height, blood pressure, social class, education level, alcohol intake, smoking status, axial length, intraocular pressure, and lens status. Models were linearly adjusted for typical scan score to handle scans with atypical retardation. RESULTS There were complete data from 11,030 eyes of 6309 participants with mean age 68 years (48-90 years). Older age (-1.53 μm/decade [95% confidence interval {CI} -1.73, -1.33], P < 0.001), male sex (-0.44 μm [95% CI -0.04, -0.84], P = 0.031), shorter axial length (-0.15 μm/mm [95% CI -0.02, -0.28], P = 0.024), and pseudophakia (-0.49 μm [95% CI -0.94, -0.04], P = 0.033) were associated with thinner RNFL after adjustment for possible confounders. Higher BMI was associated with a thinner RNFL in men only (-0.30 μm/5 kg/m(2) [95% CI -0.58, -0.02], P = 0.039). CONCLUSIONS This analysis of associations with RNFL thickness in a largely healthy population may provide insight into the determinants of glaucoma, suggesting higher risk in those who are older, in men, and in men with a higher BMI.

Corneal Biomechanical Properties and Glaucoma-Related Quantitative Traits in the EPIC-Norfolk Eye Study

PURPOSE We examined the association of corneal hysteresis (CH) with Heidelberg retina tomograph (HRT)- and Glaucoma Detection with Variable Corneal Compensation scanning laser polarimeter (GDxVCC)-derived measures in a British population. METHODS The EPIC-Norfolk Eye Study is nested within a multicenter cohort study--the European Prospective Investigation of Cancer. Ocular response analyzer (ORA), HRT3, and GDxVCC measurements were taken at the research clinic. Three ORA measurements were taken per eye, and the single best value used. Participants meeting predefined criteria were referred for a second examination, including Goldmann applanation tonometry (GAT) and central corneal thickness (CCT) measurement. Generalized estimating equation models were used to examine the associations of CH with HRT and GDxVCC parameters, adjusted for disc area. The GDxVCC analyses were adjusted further for typical scan score to handle atypical retardation. RESULTS There were complete research clinic data from 5134 participants. Corneal hysteresis was associated positively with HRT rim area (P < 0.001), and GDxVCC retinal nerve fiber layer (RNFL) average thickness (P = 0.006) and modulation (P = 0.003), and associated negatively with HRT linear cup-to-disc ratio (LCDR, P < 0.001), after adjustment for Goldmann-correlated IOP and other possible confounders. In the 602 participants undergoing the second examination, CH was associated negatively with LCDR (P = 0.008) after adjustment for GAT, CCT, and other possible confounders. CONCLUSIONS Lower CH was associated with HRT and GDxVCC parameters in a direction that is seen in glaucoma and with ageing. Further research is required to establish if this is a causal relationship, or due to residual confounding by age, IOP, or CCT.

Cross Sectional and Longitudinal Associations between Cardiovascular Risk Factors and Age Related Macular Degeneration in the EPIC-Norfolk Eye Study.

Purpose To examine the cross sectional and longitudinal relationship between cardiovascular risk factors and age-related macular degeneration (AMD) in a large British cohort study. Methods The EPIC Norfolk Eye study is nested in a larger prospective cohort study. Data on cardiovascular risk factors were collected at baseline (1993-1997) and follow up (2006-2011) via clinical examination, validated lifestyle questionnaires and serum blood samples. AMD was ascertained using standardised grading of fundus photographs at the follow up. Logistic regression was used to examine associations between baseline and follow up risk factors with AMD. Results 5,344 pairs (62.0% of total 8623) of fundus photographs were of sufficient quality for grading of AMD in participants with mean age of 67.4 years old (range 44-91) at diagnosis. There were 28 cases of late AMD (0.5%, 95% confidence interval (CI)=0.3-0.8%) and 645 cases of early AMD (12.1%, 95%CI=11.2-13.0.%). In multivariable analysis, older people with higher levels of baseline high density lipoprotein- cholesterol (HDL-C ) and C-reactive protein (CRP) were more likely to have any signs of AMD, after adjusting for sex, education, smoking, and systolic blood pressure. In cross sectional analysis, only older age and higher HDL were significantly associated with AMD. Conclusions We have found that older age and higher levels of CRP and HDL-C were associated with increased odds of AMD in this population in the longitudinal analysis, but older age and HDL-C, not CRP was significantly associated with AMD in the cross sectional analysis. The prevalence of AMD in this cohort was low compared to other cohorts in Europe, the US and Australia, and probably reflects the some selection biases in follow up participation as well as the low rate of smoking among our healthy participants.

Associations with Intraocular Pressure in a Large Cohort: Results from the UK Biobank

Purpose To describe the associations of physical and demographic factors with Goldmann-correlated intraocular pressure (IOPg) and corneal-compensated intraocular pressure (IOPcc) in a British cohort. Design Cross-sectional study within the UK Biobank, a large-scale multisite cohort study in the United Kingdom. Participants We included 110 573 participants from the UK Biobank with intraocular pressure (IOP) measurements available. Their mean age was 57 years (range, 40–69 years); 54% were women, and 90% were white. Methods Participants had 1 IOP measurement made on each eye using the Ocular Response Analyzer noncontact tonometer. Linear regression models were used to assess the associations of IOP with physical and demographic factors. Main Outcome Measures The IOPg and IOPcc. Results The mean IOPg was 15.72 mmHg (95% confidence interval [CI], 15.70–15.74 mmHg), and the mean IOPcc was 15.95 mmHg (15.92–15.97 mmHg). After adjusting for covariates, IOPg and IOPcc were both significantly associated with older age, male sex, higher systolic blood pressure (SBP), faster heart rate, greater myopia, self-reported glaucoma, and colder season (all P < 0.001). The strongest determinants of both IOPg and IOPcc were SBP (partial R2: IOPg 2.30%, IOPcc 2.26%), followed by refractive error (IOPg 0.60%, IOPcc 1.04%). The following variables had different directions of association with IOPg and IOPcc: height (−0.77 mmHg/m IOPg; 1.03 mmHg/m IOPcc), smoking (0.19 mmHg IOPg, −0.35 mmHg IOPcc), self-reported diabetes (0.41 mmHg IOPg, −0.05 mmHg IOPcc), and black ethnicity (−0.80 mmHg IOPg, 0.77 mmHg IOPcc). This suggests that height, smoking, diabetes, and ethnicity are related to corneal biomechanical properties. The increase in both IOPg and IOPcc with age was greatest among those of mixed ethnicities, followed by blacks and whites. The same set of covariates explained 7.4% of the variability of IOPcc but only 5.3% of the variability of IOPg. Conclusions This analysis of associations with IOP in a large cohort demonstrated that some variables clearly have different associations with IOPg and IOPcc, and that these 2 measurements may reflect different biological characteristics.

Glaucoma and intraocular pressure in EPIC-Norfolk Eye Study: cross sectional study

Objectives To report the distribution of intraocular pressure (IOP) by age and sex and the prevalence of glaucoma. Design Community based cross sectional observational study. Setting EPIC-Norfolk cohort in Norwich and the surrounding rural and urban areas. Participants 8623 participants aged 48-92 recruited from the community who underwent ocular examination to identify glaucoma. Main outcome measures Prevalence and characteristics of glaucoma, distribution of IOP, and the sensitivity and specificity of IOP for case finding for glaucoma. Results The mean IOP in 8401 participants was 16.3 mm Hg (95% confidence interval 16.2 mm Hg to 16.3 mm Hg; SD 3.6 mm Hg). In 363 participants (4%), glaucoma was present in either eye; 314 (87%) had primary open angle glaucoma. In the remaining participants, glaucoma was suspected in 607 (7%), and 863 (10.0%) had ocular hypertension. Two thirds (242) of those with glaucoma had previously already received the diagnosis. In 76% of patients with newly diagnosed primary open angle glaucoma (83/107), the mean IOP was under the threshold for ocular hypertension (21 mm Hg). No one IOP threshold provided adequately high sensitivity and specificity for diagnosis of glaucoma. Conclusions In this British community, cases of glaucoma, suspected glaucoma, and ocular hypertension represent a large number of potential referrals to the hospital eye service. The use of IOP for detection of those with glaucoma is inaccurate and probably not viable.

Retinal Nerve Fiber Layer Measures and Cognitive Function in the EPIC-Norfolk Cohort Study

Purpose We examined the relationship between retinal nerve fiber layer (RNFL) thickness and cognitive function in a population of older British adults. Methods Participants of the European Prospective Investigation of Cancer (EPIC) Norfolk cohort study underwent ophthalmic and cognitive assessment. Measurements of RNFL thickness were made using the Heidelberg Retina Tomograph (HRT). Cognitive testing included a short form of the Mini-Mental State Examination (SF-MMSE), an animal naming task, a letter cancellation task, the Hopkins Verbal Learning Test (HVLT), the National Adult Reading Test (NART), and the Paired Associates Learning Test. Multivariable linear regression models were used to assess associations of RNFL thickness with cognitive test scores, adjusted for age, sex, education level, social class, visual acuity, axial length, and history of cataract surgery. Results Data were available from 5563 participants with a mean age of 67 years. A thicker HRT-derived RNFL thickness was associated with better scores for the SF-MMSE (0.06; 95% confidence interval [CI], [0.02, 0.10], P = 0.005), HVLT (0.16, 95% CI [0.03, 0.29]; P = 0.014), and NART (−0.24, 95% CI [−0.46, −0.02], P = 0.035). The associations of RNFL thickness with SF-MMSE and HVLT remained significant following further adjustment for NART. Conclusions We found a significant association between HRT-derived RNFL thickness and scores from cognitive tests assessing global function, recognition, learning, episodic memory, and premorbid intelligence. However, the associations were weak and not currently of predictive value. Further research is required to confirm and clarify the nature of these associations, and identify biological mechanisms.

Laser Scanning Tomography in the EPIC-Norfolk Eye Study: Principal Components and Associations

PURPOSE To describe Heidelberg Retina Tomograph (HRT) measures, their principal components, and their associations in a British population. METHODS The European Prospective Investigation of Cancer (EPIC)-Norfolk Eye Study is nested within a multicenter cohort study. Measurements were taken with the HRT-2 and the software subsequently updated to yield HRT-3 parameters. Principal components analysis (PCA) was used to identify distinct components of the HRT variables. Generalized estimating equation models were used to examine associations of these components with age, sex, height, body mass index (BMI), blood pressure, social class, education, alcohol intake, smoking status, axial length, IOP, and lens status. RESULTS Complete data were available from 10,859 eyes of 6430 participants with a mean age of 68 years. Principal components analysis identified three components with an eigenvalue greater than 1, explaining 79.9% of the variance of all the HRT measures. These were named cup, retinal nerve fiber layer (RNFL), and rim based on the factor loadings they were most correlated with. Older age was significantly associated with a greater cup (P = 0.003), smaller RNFL (P < 0.001), and smaller rim (P < 0.001). Female sex (P = 0.001), higher education (P < 0.001), and shorter axial length (P < 0.001) were associated with a greater RNFL. Lower BMI and higher IOP were associated with a greater cup (both, P < 0.001) and a smaller rim (BMI, P = 0.001; IOP, P < 0.001). CONCLUSIONS Heidelberg Retina Tomograph measures in this cohort were largely explained by three principal components related to optic disc cup, RNFL, and rim. Associations with cup and rim were distinct to associations with RNFL, suggesting different underlying determinants.