February 2013
Volume 54, Issue 2
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Clinical and Epidemiologic Research  |   February 2013
Impact of Glaucoma Severity and Laterality on Vision-Specific Functioning: The Singapore Malay Eye Study
Author Affiliations & Notes
  • Errol W. Chan
    From the Department of Ophthalmology, National University Hospital, National University Health System, Singapore, Republic of Singapore; the
  • Peggy P. C. Chiang
    Singapore Eye Research Institute, National University of Singapore, Singapore, Republic of Singapore;
    Duke-NUS Graduate Medical School, Singapore, Republic of Singapore; the
  • Tien Y. Wong
    From the Department of Ophthalmology, National University Hospital, National University Health System, Singapore, Republic of Singapore; the
    Singapore Eye Research Institute, National University of Singapore, Singapore, Republic of Singapore;
    Centre for Eye Research Australia, The Royal Victorian Eye and Ear Hospital, University of Melbourne, Melbourne, Australia; and the
  • Seang M. Saw
    Singapore Eye Research Institute, National University of Singapore, Singapore, Republic of Singapore;
    Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Republic of Singapore.
  • Seng C. Loon
    From the Department of Ophthalmology, National University Hospital, National University Health System, Singapore, Republic of Singapore; the
  • Tin Aung
    From the Department of Ophthalmology, National University Hospital, National University Health System, Singapore, Republic of Singapore; the
    Singapore Eye Research Institute, National University of Singapore, Singapore, Republic of Singapore;
  • Ecosse Lamoureux
    Singapore Eye Research Institute, National University of Singapore, Singapore, Republic of Singapore;
    Centre for Eye Research Australia, The Royal Victorian Eye and Ear Hospital, University of Melbourne, Melbourne, Australia; and the
  • Corresponding author: Ecosse Lamoureux, Centre for Eye Research Australia, Department of Ophthalmology, University of Melbourne, East Melbourne, VIC 8002; ecosse@unimelb.edu.au
Investigative Ophthalmology & Visual Science February 2013, Vol.54, 1169-1175. doi:10.1167/iovs.12-10258
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      Errol W. Chan, Peggy P. C. Chiang, Tien Y. Wong, Seang M. Saw, Seng C. Loon, Tin Aung, Ecosse Lamoureux; Impact of Glaucoma Severity and Laterality on Vision-Specific Functioning: The Singapore Malay Eye Study. Invest. Ophthalmol. Vis. Sci. 2013;54(2):1169-1175. doi: 10.1167/iovs.12-10258.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose.: We determined the impact of glaucoma severity and laterality on vision-specific functioning (VF) in an Asian population.

Methods.: The Singapore Malay Eye Study (SiMES) was a population-based cross-sectional study of 3280 Malays aged 40 to 80 years. VF was assessed using the VF-11 questionnaire. Associations between VF-11 score and glaucoma clinical indices (glaucoma severity in better and worse eyes, and laterality) were determined by multivariate regression modeling. Glaucoma severity was defined as mild, moderate, advanced, and severe based on the Hodapp-Anderson-Parish system. Rasch analysis was used to validate the VF-11 and determine its psychometric properties.

Results.: Of 926 persons analyzed, 123 had glaucoma (13.3% glaucoma prevalence in analyzed sample). The mean ± SD VF score was 3.64 ± 1.05 log of odds units (Logits). In multivariate models adjusting for sociodemographic, ocular, and systemic variables, poorer VF was associated with increasingly worse eye visual field loss (β = 0.016, 95% confidence interval [CI] 0.004–0.029, P < 0.001), but not that of the better eye (P > 0.05). Compared to controls, VF was reduced in individuals with worse eye advanced and severe glaucoma (β = −0.65, 95% CI −1.03 to −0.28, P < 0.05), but not mild or moderate glaucoma (P > 0.05). Compared to controls, VF was reduced in unilateral (β = −0.29, 95% CI −0.54 to −0.04, P < 0.05), but not bilateral glaucoma (P > 0.05). These associations remained significant after adjusting for presenting and best-corrected visual acuity.

Conclusions.: Among Singaporean Malays, unilateral, and advanced and severe glaucoma in the worse eye significantly impacts on VF. Identifying early-stage glaucoma, preventing progression, and visual rehabilitation in advanced glaucoma are important aspects of glaucoma management.

Introduction
Glaucoma is a leading cause of poor vision-specific functioning and irreversible blindness. 113 In 2010, 65 million individuals worldwide were estimated to be affected by glaucoma, with the majority in Asia. In Singapore, the Tanjong Pagar Eye Study reported a 3.2% 3 population prevalence of glaucoma in Chinese individuals, and the Singapore Malay Eye Study (SiMES) 4 reported a similar rate of 3.4% in Malays. 
It is well known that glaucoma impacts a wide spectrum of activities. The general and vision-specific quality of life is poorer in individuals with glaucoma. 57 Glaucoma sufferers have significant difficulty with key daily living activities, such as reading, 8 walking, 9,10 and driving, 11 and have a higher likelihood of motor vehicle accidents, 12 falls, 13 nursing home admissions, 14 anxiety, and depression 15 compared to people without the condition. Recent data have indicated that hypertension, hyperlipidemia, stroke, and diabetes also are more common in glaucoma sufferers; these conditions, in turn, may affect quality of life as well. 16 Furthermore, the financial burden of the disease also is considerable. 17  
While the qualitative impact of glaucoma is unquestionable, few studies have investigated the level at which glaucoma produces significant visual disability. Individuals with early glaucoma with limited visual field losses may not experience the same magnitude of disability as individuals with advanced glaucoma and tunneled vision. This information may be important for glaucoma management, for example, to identify patients who require escalation of glaucoma treatment, or visual rehabilitation. 18 Furthermore, the clinical measures in glaucoma (e.g., better or worse eye visual field losses) that correlate most robustly with visual functioning (VF) are unclear. 5,6 In addition, ethnic or population differences may impact the level of disease severity linked with disability, illustrated in diabetic retinopathy by the comparative findings of the SiMES 19 and the Los Angeles Latino Eye Study (LALES). 20 However, population-based data on VF in glaucoma mostly have come from a few studies performed in Western countries, 68,10,11 with data from Asia almost nonexistent. 
There are 400 million Malays in Southeast Asia alone. As this ethnic group has distinctive sociocultural characteristics, the impact of glaucoma on VF may be unique to this population. 21,22 The aim of our study was to determine the impact of glaucoma parameters used in clinical practice (glaucoma severity in the better and worse eyes, and glaucoma laterality) on VF in the Singapore Malay population using the Vision-specific Functioning Scale (VF-11), previously validated for this population. 19  
Methods
Study Population
The SiMES was a population-based evaluation of 3280 Malay participants (78.7% response rate) aged 40 to 80 years. The study design and epidemiologic data have been described previously. 4,23,24 This study was approved by the Institutional Review Board of the Singapore Eye Research Institute and performed in accordance with the tenets of the Declaration of Helsinki. 
The age- and sex-standardized prevalence of glaucoma was 3.4% in the SiMES population. 4 However, the glaucoma evaluation strategy of SiMES (described below) was based on a method used in prevalence surveys and did not involve visual field testing for all participants. 4 As such, we first identified 945 cases with available visual field tests. Participants with concomitant ocular conditions that would impact VF or performance on a visual field test then were excluded. Participants with refractive errors, cataracts, mild-to-moderate non-proliferative diabetic retinopathy, or early age-related macular degeneration were included. No significant differences were noted between included and excluded participants in terms of age, sex, smoking status, educational level, monthly individual income, or medical comorbidities (P > 0.05). A final group of 926 participants (123 with glaucoma, 91 with ocular hypertension, and 712 without glaucoma) were included in this analysis. 
Glaucoma Evaluation Procedure
Glaucoma was assessed in SiMES based on a similar protocol used in the Tanjong Pagar Eye Survey and Blue Mountains Eye Study. 3,25 A comprehensive clinical examination involving slit-lamp biomicroscopy and IOP measurement was performed for all participants. IOP was measured with a Goldmann applanation tonometer. Post-dilation, vertical cup-disc ratios (VCDR) were determined by the study ophthalmologists with a +78 diopter (D) lens at 16× magnification with a measuring graticule (Haag-Streit, Bern, Switzerland). 3,25 Digital retinal images centered on the optic disc (Early Treatment of Diabetic Retinopathy [ETDRS], Standard Field 1) were captured after dilation (Canon CR-DGi 10D SLR back; Canon, Tokyo, Japan). Predilation static and dynamic gonioscopy with a Goldmann 2-mirror gonioscope (model 903, Haag-Streit) was performed for cases with IOP (intraocular pressure) >21 mm Hg, VCDR >0.6 or VCDR asymmetry >0.2, shallow peripheral anterior chamber (van Herick grade 2 or less), anterior segment signs of previous acute primary angle closure or secondary glaucoma, and one in five randomly-selected participants from the rest of the sample. 20 This evaluation identified “glaucoma suspects” (n = 430), defined by at least one of the following characteristics: IOP >21 mm Hg, VCDR >0.6 or VCDR asymmetry >0.2, pupil or endothelial deposits consistent with pseudoexfoliation or pigment dispersion syndrome, “occludable” angles (absence of posterior trabecular meshwork ≥180° on static gonioscopy), peripheral anterior synechiae, and a known glaucoma history. 4,23  
Automated static perimetry was performed using the Humphrey Visual Field (HVF) Analyzer II (SITA 24-2 Standard; Carl Zeiss Meditec, Oberkochen, Germany) on “glaucoma suspects” and one in 10 randomly selected participants before the ophthalmic examination. Visual field tests were repeated if test indices were unreliable (i.e., fixation loss >20%, false positive >33%, and/or false negative >33%). A second set of IOP, gonioscopy, and visual field findings for “glaucoma suspects” also were obtained in a separate-day examination. 
Glaucoma Definition
Glaucoma was defined according to the International Society for Geographic and Epidemiological Ophthalmology. 23,26 Final identification, adjudication, and classification of glaucoma status and type was performed by a glaucoma specialist (TA). The glaucoma evaluation strategy described above identified 150 (4.6%) with glaucoma and 91 (2.9%) with ocular hypertension, as described in the original study. 3  
Glaucoma clinical severity was assessed for each eye based on mean deviation (MD) thresholds from the modified Hodapp-Anderson-Parish classification scheme. 27,28 Stage 0 was equivalent to none or minimal visual field defects, and included ocular hypertension (OHT) and eyes not meeting criteria for Stage 1. Stages 1 through 4 indicated early (MD ≥−6.00 dB), moderate (−6.01 to −12.00 dB), advanced (−12.01 to −20.00 dB), and severe (−20.00 dB) glaucoma stages, respectively. 
Assessment of Vision-Specific Functioning
The VF-11 used in the SiMES has been described previously. 13,19,29,30 The VF-11 comprises 11 questions assessing difficulties with the following daily activities: seeing stairs, seeing street or shops signs, recognizing people, watching television, cooking, playing cards or mahjong, reading newspapers, filling out lottery forms, reading small print, driving in the day, and driving at night (Table 1). Nine of the VF-11 items were rated on a scale from 0 (no difficulty) to 4 (unable to perform activity), while the 2 driving items had 3 responses (1, no difficulty; 2, little difficulty; and 3, most difficulty). This was administered through face-to-face interviews by trained and bilingual research assistants in English and/or Malay. Rasch analysis was used to determine the psychometric properties (i.e., validity and reliability) of the VF-11 questionnaire. Rasch analysis was performed with the RUMM2020 (RUMM 2020; RUMM Laboratory, Duncraig, Australia) and the Andrich single rating scale. 31 Rasch analysis is a modern psychometric method that approximates raw ordinal scores of the VF-11 questionnaire into interval-level measurement (expressed in log of odds units, or logits), permitting the use of parametric statistical techniques. It calculates item difficulty (item measure) in relation to person ability (person measure) by placing both on the same linear continuum. A high person measure (in logits) indicates that the participant possesses a high level of the assessed latent trait (e.g., vision-specific functioning). Rasch analysis also provides insight into the psychometric properties of a scale, such as how well items fit the underlying latent trait being measured (i.e., glaucoma-specific QoL), how well items discriminate between the respondents, how well item difficulty targets person ability, and the appropriateness of the response scale used. 32 Validity of the VF-11 was assessed for item fit, behavior of response categories (i.e., if higher categories represented better functioning), measurement precision (minimum person separation value of 2.0), and unidimensionality (i.e., whether the items form a unitary latent trait). 
Table 1. 
 
Item Content of the VF-11 Questionnaire
Table 1. 
 
Item Content of the VF-11 Questionnaire
Item Number Item Description
1 Difficulty in reading small print in the telephone book even with glasses?
2 Difficulty in reading newspaper size print even with glasses?
3 Difficulty in recognizing friends when you meet them while shopping even with glasses?
4 Difficulty seeing stairs even with glasses?
5 Difficulty in reading street signs or shop signs even with glasses?
6 Difficulty in filling out 4-D or Toto forms even with glasses?
7 Difficulty in playing games—chess or cards—even with glasses?
8 Difficulty in cooking even with glasses?
9 Difficulty in watching television even with glasses?
10 Difficulty in driving during the day because of vision?
11 Difficulty in driving at night time because of vision?
Measurement of Vision and Other Covariates
Presenting visual acuity (PVA) with the participant's habitual (“walk-in”) optical correction was tested using a logarithm of the minimum angle of resolution (LogMAR) vision chart (Lighthouse International, New York, NY) at 4 meters for each eye. 33 The best-corrected visual acuity (BCVA) also was assessed after subjective refraction. Visual impairment was scored as normal (<0.3 LogMAR), mild-to-moderate vision loss (0.3–1.0 LogMAR), and severe vision loss (≥1.0 LogMAR). 
A standardized interviewer-administered questionnaire was used to elicit information on demographic data (age, sex), socioeconomic measures (e.g., education, individual monthly income), and self-reported history of systemic diseases (e.g., stroke, myocardial infarction, angina). Other ocular conditions (e.g., cataract, age-related macular degeneration, refractive errors, diabetic retinopathy) and systemic comorbidities (e.g., hyperlipidemia, diabetes, hypertension, chronic kidney disease) were assessed as described previously. 13,19,23 Cataract was graded from lens photographs according to the Wisconsin cataract grading system. 34 Age-related macular degeneration was graded from retinal photographs according to the Wisconsin Age-related Maculopathy grading system. 35 Diabetic retinopathy was graded from retinal photographs according to the modified Arlie House classification system from the ETDRS Study. 36 Nonfasting venous blood samples were drawn and sent for assay of levels of various lipid fractions, serum creatinine, and serum glucose. Hyperlipidemia was defined as total cholesterol of >6.2 mmol/L or more, or use of lipid-lowering medications. Diabetes was defined by a random glucose ≥11.1 mmol/L, use of diabetic medication, or a physician diagnosis of diabetes. Hypertension was defined as systolic blood pressure of 140 mm Hg, diastolic blood pressure >90 mm Hg, or use of antihypertensive medication. Chronic kidney disease was defined as estimated glomerular filtration rate <60 mL/min/1.73 m2. The estimated glomerular filtration rate was estimated from serum creatinine using the Modification of Diet in Renal Disease equation as described previously. 23  
Statistical Analyses
Descriptive statistical analyses were used to characterize participants' sociodemographic and clinical data. The overall VF score linearly estimated after Rasch analysis was fitted to linear regression models and used t-based 95% confidence intervals (CIs) for the regression coefficients. The associations between VF and glaucoma severity in the better and worse eyes (in terms of mean deviation as a continuous variable and Hodapp-Anderson-Parish categories), and glaucoma laterality were assessed in three multivariate regression models each. In Model 1, adjustment was made for sociodemographic variables (age, sex, individual monthly income, and educational level), other ocular conditions (cataract, mild-to-moderate diabetic retinopathy, refractive errors), and systemic illnesses (myocardial infarction, chronic kidney disease, hypertension, stroke). In Model 2, adjustment was made for all the above covariates and PVA in the better eye. In Model 3, adjustment was made for sociodemographic, ocular, and systemic factors, and BCVA. Statistical analyses were performed with STATA version 11.0 (StataCorp, College Station, TX). 
Results
Participants' Characteristics
The sociodemographic and clinical characteristics of the 926 participants are shown in Table 2. The mean ± SD age was 56.83 ± 10.93 years. The majority of individuals were male (54.7%), had primary school or lower education (71.8%), and a monthly individual income of <SGD$1000 (52.7%). Nearly half (49.7%) of the participants were either retired or not working at the time of the study. Most individuals (94.6%) had normal PVA in the better eye, and 89.2% had normal PVA in the worse eye. The overall VF mean score for the whole population was 3.64 ± 1.05 logits (range −0.92–4.48). The most common systemic comorbidities in this population were hypertension (65.7%), chronic kidney disease (19.3%), and myocardial infarction (6.3%). 
Table 2. 
 
Sociodemographic and Systemic Participants and Stratified VF Score Analyzed by Univariate Analyses (n = 926)
Table 2. 
 
Sociodemographic and Systemic Participants and Stratified VF Score Analyzed by Univariate Analyses (n = 926)
Characteristic No. (%) VF Score (± SD) P Values*
Sex 0.0050
 Male 503 (54.3) 3.73 (±0.46)
 Female 523 (45.7) 3.54 (±0.51)
Age, y <0.0001†
 40–49 272 (29.4) 3.72 (±0.93)
 50–59 307 (33.2) 3.75 (±0.96)
 60–69 176 (19.0) 3.67 (±1.09)
 70–80 171 (18.4) 3.28 (±1.25)
Education <0.0001
 Primary or lower 662 (71.6) 3.55 (±1.09)
 Primary or higher 263 (28.4) 3.86 (±0.88)
Monthly individual income
  <1000 482 (52.5) 3.53 (±1.10) 0.0006‡
 1000–≤2000 218 (23.8) 3.78 (±0.90)
  >2000 133 (14.5) 3.89 (±0.87)
 Retired 85 (9.2) 3.66 (±1.11)
Smoking status 0.672
 Never smoked 515 (55.7) 3.67 (±1.00)
 Current smokers 224 (24.2) 3.63 (±1.03)
 Past smokers 185 (20.0) 3.58 (±1.17)
Nonocular comorbid conditions
 Chronic kidney disease 179 (19.3) 3.47 (±1.19) 0.0183
 Angina 32 (3.5) 3.69 (±1.00) 0.806
 Myocardial infarction 58 (6.3) 3.38 (±1.35) 0.0526
 Stroke 15 (1.6) 2.89 (±0.39) 0.0047
 Hypertension 609 (65.7) 3.58 (±1.08) 0.0288
There were 123 individuals with glaucoma among the 926 participants analyzed (proportion of glaucoma in 926 participants, 13.3%). Of 926 participants, 9.4% (n = 87) and 3.9% (n = 36) had unilateral and bilateral glaucoma, respectively. Mild, moderate, advanced, and severe glaucoma in the worse eye were present in 5.0% (n = 46), 3.5% (n = 32), 2.4% (n = 22), and 2.2% (n = 20), respectively. Primary open-angle glaucoma (POAG) was present in 90 (9.7%) participants and non-POAG (primary angle closure glaucoma and pseudoexfoliative glaucoma) in 33 (2.6%) participants. 
Validation of the VF-11 Questionnaire in Singaporeans Malays with Glaucoma
All 926 participants answered the VF-11 questionnaire. First, all VF-11 scores (i.e., patient responses) were reversed for Rasch analysis purposes giving participants with good vision functioning ability the higher score and vice versa. Second, the 11 items then were fitted to the Rasch model. Two items demonstrated item misfit, that is, having infit residual values >1.3. These were items 10 (“Do you have difficulty in driving during the day because of vision”?) and 11 (“Do you have difficulty in driving at night time because of vision”?). This implies that these two questions were the least likely to apply to this group of participants. These two items were removed and the remaining nine items all subsequently showed values <1.3. The mean ± SD person and item fit residual values were 1.21 and 0.56, respectively, suggesting that the modified VF-11 has substantial validity with mean and SD approaching 0 and 1, respectively. The person separation reliability value was 1.89 (criteria >2.0), indicating a level of ability to differentiate between different strata of person ability. Unidimensionality also was observed, confirming that the instrument measures the one underlying trait (VF) it purports to measure. 
Association between Glaucoma and Vision-Specific Functioning
Poorer VF was univariately associated with sex, age, education, monthly income, chronic kidney disease, stroke and hypertension, and cataract (all P < 0.05, Tables 2, 3). PVA and BCVA in the better and worse eyes were associated individually with poorer VF (all P < 0.001). All glaucoma endpoints showed significantly poorer VF: glaucoma (P < 0.001), glaucoma severity stage in the better (P = 0.0036) and worse (P < 0.001) eyes, and laterality (P < 0.001). Compared to individuals with no glaucoma or OHT in the worse eye, only individuals with Stage 3 (advanced) or Stage 4 (severe) glaucoma in the worse eye had poorer VF (Stage 3: 2.85 ± 1.47, Stage 4: 2.80 ± 1.73, no glaucoma or OHT: 3.70 ± 0.99, P < 0.05). However the difference in VF in the better eye when comparing between individuals with Stage 3 or 4 glaucoma, and no glaucoma or OHT was not statistically significant (Stage 3 or 4: 3.07 ± 1.21, no glaucoma or OHT: 3.70 ± 0.99, P > 0.05). Compared to individuals with no glaucoma or OHT, individuals with unilateral glaucoma, but not bilateral glaucoma, had poorer VF (unilateral: 3.23 ± 1.40, bilateral: 3.39 ± 1.14, no glaucoma or OHT: 3.69 ± 1.00, P < 0.05 only for unilateral versus no glaucoma or OHT, Table 3). 
Table 3. 
 
Clinical Characteristics of Participants and Stratified VF Score Analyzed by Univariate Analyses (n = 926)
Table 3. 
 
Clinical Characteristics of Participants and Stratified VF Score Analyzed by Univariate Analyses (n = 926)
Characteristic No. (%) VF Score (± SD) P Values*
Ocular comorbid conditions
 Diabetic retinopathy (mild-to-moderate severity) 3 (0.3) 2.67 (±1.59) 0.1075
 Cataracts 327 (35.3) 3.46 (±1.16) 0.0001
 Refractive errors 217 (23.6) 3.64 (±0.98) 0.898
Presenting visual impairment (worse eye logMAR) <0.0001†
 Normal 809 (89.2) 3.74 (±0.95)
 Mild 54 (6.0) 3.22 (±1.18)
 Moderate-to-severe 44 (4.9) 2.96 (±1.26)
Presenting visual impairment (better eye logMAR) <0.0001†
 Normal 876 (94.6) 3.70 (±0.98)
 Mild 31 (33.4) 2.55 (±1.58)
 Moderate-to-severe 17 (1.8) 2.58 (±1.50)
Best corrected visual impairment (worse eye logMAR) <0.0001†
 Normal 809 (89.2) 3.74 (±0.95)
 Mild 54 (6.0) 3.22 (±1.18)
 Moderate-to-severe 44 (4.9) 2.96 (±1.26)
Best corrected visual impairment (better eye logMAR) <0.0001†
 Normal 876 (94.6) 3.70 (±0.98)
 Mild 31 (33.4) 2.54 (±1.58)
 Moderate-to-severe 17 (1.8) 2.58 (±1.50)
Presence of glaucoma 123 (13.3) 3.28 (±1.31) <0.0001
Laterality of glaucoma 0.0001‡
 No glaucoma or ocular hypertension 803 (86.7) 3.69 (±1.00)
 Unilateral 87 (9.4) 3.23 (±1.40)
 Bilateral 36 (3.9) 3.39 (±1.14)
Severity of glaucoma in the worse eye <0.0001§
 No glaucoma or ocular HT 806 (87.0) 3.70 (±0.99)
 Stage 1 (mild) 46 (5.0) 3.45 (±1.15)
 Stage 2 (moderate) 32 (3.5) 3.55 (±1.04)
 Stage 3 (advanced) 22 (2.4) 2.85 (±1.47)
 Stage 4 (severe) 20 (2.2) 2.80 (±1.73)
Severity of glaucoma in the better eye 0.0036¶
 No glaucoma or ocular hypertension 809 (88.3) 3.70 (±0.99)
 Stage 1 (mild) 69 (7.5) 3.41 (±1.09)
 Stage 2 (moderate) 25 (2.7) 3.26 (±1.51)
 Stage 3–Stage 4 (advanced to severe) 13 (1.4) 3.07 (±1.21)
Glaucoma subtypes 0.0002||
 No glaucoma or ocular hypertension 805 (86.7) 3.70 (±0.99)
 Non-POAG (primary angle closure glaucoma, pseudoexfoliative glaucoma) 33 (3.6) 3.26 (±1.40)
 POAG 90 (9.7) 3.28 (±1.29)
A multivariate regression model adjusting for sociodemographic (age, sex, education, income), ocular (cataract, mild-to-moderate diabetic retinopathy, refractive errors), and systemic factors (chronic kidney disease, hypertension, stroke) showed an independent association between poorer VF and more negative MD scores (i.e., more severe visual field loss) of the worse eye (β = 0.025, 95% CI 0.012–0.038, P < 0.001) (Table 4). Adjusting for these covariates in Model 1 showed that compared to controls, persons with Stage 3 or 4 glaucoma in the worse eye (β = −0.65, 95% CI −1.03 to −0.28, P < 0.05), and unilateral glaucoma (β = −0.29, 95% CI −0.54 to −0.04, P < 0.05) had significantly poorer VF. The above associations remained significant after inclusion of either PVA or BCVA (Models 2 and 3). After controlling for PVA, VF still remained associated independently with worse eye MD as a continuous variable (β = 0.016, 95% CI 0.004–0.029, P < 0.001), Stage 3 or 4 glaucoma in the worse eye (β = −0.51, 95% CI −0.90 to −0.11, P < 0.05), and unilateral glaucoma (β = −0.29, 95% CI −0.53 to −0.04, P < 0.01). In all models, VF was not associated with better eye glaucoma severity in terms of MD scores as a continuous parameter, or when categorized in the Hodapp-Anderson-Parish system (P > 0.05). 
Table 4. 
 
Difference in Overall VF Score in Glaucoma in 3 Multivariate Linear Regression Models
Table 4. 
 
Difference in Overall VF Score in Glaucoma in 3 Multivariate Linear Regression Models
Model 1* Coefficient (95% CI) Model 2† Coefficient (95% CI) Model 3‡ Coefficient (95% CI)
Glaucoma laterality
 Normal 3.66 (1.00) 3.66 (0.99) 3.66 (0.99)
 Unilateral§ −0.29 (−0.54, −0.04) −0.29 (−0.53, −0.04) −0.29 (−0.53, −0.04)
 Bilateral −0.20 (−0.57, 0.16) −0.27 (−0.62, 0.09) −0.27 (−0.62, 0.09)
Severity of glaucoma (worse eye)
 No glaucoma/OHT – Stage 0 3.69 (1.00) 3.71 (0.96) 3.71 (0.96)
 Stage 1 −0.24 (−0.55, 0.07) −0.19 (−0.50, 0.13) −0.19 (−0.50, 0.13)
 Stage 2 0.03 (−0.35, 0.41) −0.04 (−0.41, 0.34) −0.04 (−0.41, 0.34)
 Stage 3 and Stage 4§ −0.65 (−1.03, −0.28) −0.51 (−0.90, −0.11) −0.51 (−0.90, −0.11)
Severity of glaucoma (better eye)
 No glaucoma/OHT – Stage 0 3.70 (0.99) 3.70 (0.98) 3.70 (0.98)
 Stage 1 −0.22 (−0.48, 0.04) −0.27 (−0.53, −0.006) −0.27 (−0.53, −0.006)
 Stage 2 −0.25 (−0.71, 0.21) −0.27 (−0.73, 0.19) −0.27 (−0.73, 0.19)
 Stage 3 and Stage 4 −0.40 (−1.00, 0.20) −0.41 (−1.03, 0.22) −0.41 (−1.03, 0.22)
Discussion
To our knowledge, this is the first population-based study among Asian Malays evaluating the impact of glaucoma, and its severity and laterality on VF using the VF-11, a patient-reported outcomes instrument validated using modern psychometric techniques. Our study adds to evidence by Lamoureux et al., who found that glaucoma, among various ocular conditions (age-related macular degeneration, cataract, and uncorrected refractive error), was associated with significantly poorer VF in this population. 24 In this study, a significant worsening of VF was observed with poorer MD scores in the worse eye; however, compared to controls, individuals with advanced and severe glaucoma (Stages 3 and 4; i.e., MD −12 dB or worse) in the worse eye, and unilateral glaucoma had significantly worse vision-specific functioning. These associations persisted after controlling for other ocular conditions and visual acuity parameters. VF was associated more closely with glaucoma severity in the worse eye. 
Our results supported earlier studies demonstrating the negative impact of glaucoma on VF. 6,7 The LALES and SiMES showed that increasing visual field losses is linked with reduced VF. However, a difference lies in the glaucoma severity level when VF is reduced significantly relative to controls. The LALES showed that this was a monotonically linear relationship. In SiMES, significantly poorer vision-specific functioning occurs specifically in fairly advanced disease between moderate and severe glaucoma (MD −12 dB) in the worse eye. Pair-wise comparisons between individuals with no glaucoma, and those with mild or moderate glaucoma showed no differences in VF (Table 3). This may be explained by several hypotheses. First, in early glaucoma, compensation by the better-seeing eye may preserve VF. Second, marked reduction in central visual field, contrast sensitivity, stereopsis, glare, 37,38 or even disruption to normal cortical visual input, 39 may occur above this dB threshold, resulting in a significant decline in performance of vision-related activities. Multiple lines of evidence show that disability is observed only in advanced glaucoma, for example, in face recognition, 40 instrumental activities of daily living (IADL) 41 ; of note, motor vehicle collisions occurred more frequently in individuals with −12 dB or worse of field loss in the worse eye. 42 Third, the National Eye Institute Visual Function Questionnaire (NEI-VFQ) in the LALES and the VF-11 in SiMES differed in the spectrum of activity items measured. In our study, day and night driving items had poor fit, and were excluded from the Rasch model. In LALES, the driving item was related closely to VF. Evidence indicates that driving presents significant difficulty for individuals with glaucoma, including those with early stage disease (e.g., temporal wedge defects). 11,43,44 It is likely that in the LALES population in the United States, driving is an important activity for the elderly. Driving appears to be less important in the Singapore Malay population. As other tasks, such as watching television and reading, are largely dependent on central vision, only advanced glaucoma (with central field impairment) adversely impacts VF. This level of visual field loss may represent a clinically important endpoint where treatment should be escalated to prevent further deterioration in VF, for example, through incremental medication use or filtration surgery. 
In the Singapore Malay population, VF is driven largely by the status of the worse eye. In LALES, VF correlated with visual field loss in better and worse eyes. A better non-glaucomatous eye may not fully “compensate” for the glaucomatous worse eye, indicating importance of preserving the existing visual field in the worse eye. In persons with bilateral glaucoma who may be constrained by inconvenience, costs, or risks of additional medications or surgery, our findings may provide additional treatment considerations. Thus, in the therapeutic decision-making process, treatment of the worse eye may be prioritized more urgently. 
In our study, VF was significantly poorer only for individuals with unilateral but not bilateral glaucoma, compared to controls. Bilateral, but not unilateral glaucoma, was associated with reduced mobility and driving cessation in the Salisbury Eye Evaluation project (SEE), 7,911 and with an increased fear of falling, 45 IADL disability, 41 and poorer performance-based testing. 46,47 This could be explained that in our study, glaucoma was less severe in the worse eye for individuals with bilateral glaucoma (mean MD −4.54 ± 6.22 dB) than those with unilateral glaucoma (mean MD −5.52 ± 5.42 dB), and because VF is influenced more strongly by the worse eye in our cohort. Additionally, participants with bilateral glaucoma in our study could have different levels of adaptation and lower expectations of personal ability with activities listed in the VF-11. 
Our study showed that the association between VF and advanced or severe glaucoma remained statistically significant despite inclusion of best-corrected visual acuity in multivariate models, consistent with the pathophysiologic basis of glaucoma. Thus, appropriate identification, monitoring, and treatment are of utmost importance to retard the progression from early to advanced glaucoma. Because individuals with advanced glaucoma experience poorer VF, visual rehabilitation forms an important management priority in this group. 
There are several strengths and unique contributions of our study. First, this was a population-based evaluation with >90% of individuals with glaucoma previously undiagnosed, allowing examination of the impact of glaucoma without treatment status or knowledge of glaucoma. 4 Cases with other ocular conditions with a significant impact on visual fields or vision-specific functioning were excluded, unlike in the SEE or LALES. 6,7 Rasch analysis was used to validate the VF-11 for the SIMES population. The NEI-VFQ, despite wide usage in major quality of life studies, has not demonstrated convincingly unidimensionality. 6  
Limitations included that the VF-11, which represents only self-reported difficulties with visual-related tasks, may not capture the psychosocial and emotional impact of glaucoma. A holistic assessment of glaucoma-related disability may require an instrument more sensitive to visual field loss (e.g., Glaucoma Quality of Life-15 48 ), rather than just central vision loss. Second, our study used prevalence data, thus the longitudinal relationship between VF and visual field loss could not be determined. Third, other parameters, such as contrast sensitivity and binocular visual fields, were not evaluated. 18 Although the impact of binocular visual fields on VF has been the focus of recent research, 4850 specialized software (e.g., Progressor) required for computation of the “integrated binocular visual field” was unavailable at the time of the study, and Esterman fields were not primary measurements in the SiMES study. In clinical practice, binocular visual fields are not generated readily by Humphrey visual field analyzers. The aim of our study was to assess how standard clinical indices of glaucoma severity relate to VF, allowing clinicians to understand better when glaucoma impacts VF. 41,4547 Jampel has observed similar correlations between VF, and monocular and Esterman binocular fields, 51 and similar findings were observed in the LALES. 6 This would likely be an area of keen research interest in the future. The small number of individuals with primary angle closure or pseudoexfoliative glaucoma (n = 33) indicates that this analysis may be less applicable in these subtypes. Lastly, these findings may be less generalizable to other, that is, rural Malay populations in other parts of South East Asia. 
In conclusion, to our knowledge this is the first population-based Asian study demonstrating a negative impact of glaucoma on VF. Reduced VF in glaucoma was associated significantly with advanced and severe (Stages 3 and 4) glaucoma in the worse eye, and unilateral glaucoma, independent of refractive correction. Our data showed that identification of glaucoma in its early stages is important, as VF is relatively preserved, and IOP management is largely effective in preventing visual field deterioration. Between Stage 2 and 3 glaucoma in the worse eye suggests a point when tighter IOP management and patient counseling are indicated. Individuals with late-stage glaucoma have significant deficits in VF and highlight the importance of visual rehabilitation. These may serve as additional clinical endpoints to complement the use of standard clinical indices in glaucoma management. 
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Footnotes
 The authors alone are responsible for the content and writing of this paper.
Footnotes
 Presented at the Annual Meeting of the Association for Research in Vision and Ophthalmology, Fort Lauderdale, Florida, May 2011.
Footnotes
 Disclosure: E.W. Chan, None; P.P.C. Chiang, None; T.Y. Wong, None; S.M. Saw, None; S.C. Loon, None; T. Aung, None; E. Lamoureux, None
Table 1. 
 
Item Content of the VF-11 Questionnaire
Table 1. 
 
Item Content of the VF-11 Questionnaire
Item Number Item Description
1 Difficulty in reading small print in the telephone book even with glasses?
2 Difficulty in reading newspaper size print even with glasses?
3 Difficulty in recognizing friends when you meet them while shopping even with glasses?
4 Difficulty seeing stairs even with glasses?
5 Difficulty in reading street signs or shop signs even with glasses?
6 Difficulty in filling out 4-D or Toto forms even with glasses?
7 Difficulty in playing games—chess or cards—even with glasses?
8 Difficulty in cooking even with glasses?
9 Difficulty in watching television even with glasses?
10 Difficulty in driving during the day because of vision?
11 Difficulty in driving at night time because of vision?
Table 2. 
 
Sociodemographic and Systemic Participants and Stratified VF Score Analyzed by Univariate Analyses (n = 926)
Table 2. 
 
Sociodemographic and Systemic Participants and Stratified VF Score Analyzed by Univariate Analyses (n = 926)
Characteristic No. (%) VF Score (± SD) P Values*
Sex 0.0050
 Male 503 (54.3) 3.73 (±0.46)
 Female 523 (45.7) 3.54 (±0.51)
Age, y <0.0001†
 40–49 272 (29.4) 3.72 (±0.93)
 50–59 307 (33.2) 3.75 (±0.96)
 60–69 176 (19.0) 3.67 (±1.09)
 70–80 171 (18.4) 3.28 (±1.25)
Education <0.0001
 Primary or lower 662 (71.6) 3.55 (±1.09)
 Primary or higher 263 (28.4) 3.86 (±0.88)
Monthly individual income
  <1000 482 (52.5) 3.53 (±1.10) 0.0006‡
 1000–≤2000 218 (23.8) 3.78 (±0.90)
  >2000 133 (14.5) 3.89 (±0.87)
 Retired 85 (9.2) 3.66 (±1.11)
Smoking status 0.672
 Never smoked 515 (55.7) 3.67 (±1.00)
 Current smokers 224 (24.2) 3.63 (±1.03)
 Past smokers 185 (20.0) 3.58 (±1.17)
Nonocular comorbid conditions
 Chronic kidney disease 179 (19.3) 3.47 (±1.19) 0.0183
 Angina 32 (3.5) 3.69 (±1.00) 0.806
 Myocardial infarction 58 (6.3) 3.38 (±1.35) 0.0526
 Stroke 15 (1.6) 2.89 (±0.39) 0.0047
 Hypertension 609 (65.7) 3.58 (±1.08) 0.0288
Table 3. 
 
Clinical Characteristics of Participants and Stratified VF Score Analyzed by Univariate Analyses (n = 926)
Table 3. 
 
Clinical Characteristics of Participants and Stratified VF Score Analyzed by Univariate Analyses (n = 926)
Characteristic No. (%) VF Score (± SD) P Values*
Ocular comorbid conditions
 Diabetic retinopathy (mild-to-moderate severity) 3 (0.3) 2.67 (±1.59) 0.1075
 Cataracts 327 (35.3) 3.46 (±1.16) 0.0001
 Refractive errors 217 (23.6) 3.64 (±0.98) 0.898
Presenting visual impairment (worse eye logMAR) <0.0001†
 Normal 809 (89.2) 3.74 (±0.95)
 Mild 54 (6.0) 3.22 (±1.18)
 Moderate-to-severe 44 (4.9) 2.96 (±1.26)
Presenting visual impairment (better eye logMAR) <0.0001†
 Normal 876 (94.6) 3.70 (±0.98)
 Mild 31 (33.4) 2.55 (±1.58)
 Moderate-to-severe 17 (1.8) 2.58 (±1.50)
Best corrected visual impairment (worse eye logMAR) <0.0001†
 Normal 809 (89.2) 3.74 (±0.95)
 Mild 54 (6.0) 3.22 (±1.18)
 Moderate-to-severe 44 (4.9) 2.96 (±1.26)
Best corrected visual impairment (better eye logMAR) <0.0001†
 Normal 876 (94.6) 3.70 (±0.98)
 Mild 31 (33.4) 2.54 (±1.58)
 Moderate-to-severe 17 (1.8) 2.58 (±1.50)
Presence of glaucoma 123 (13.3) 3.28 (±1.31) <0.0001
Laterality of glaucoma 0.0001‡
 No glaucoma or ocular hypertension 803 (86.7) 3.69 (±1.00)
 Unilateral 87 (9.4) 3.23 (±1.40)
 Bilateral 36 (3.9) 3.39 (±1.14)
Severity of glaucoma in the worse eye <0.0001§
 No glaucoma or ocular HT 806 (87.0) 3.70 (±0.99)
 Stage 1 (mild) 46 (5.0) 3.45 (±1.15)
 Stage 2 (moderate) 32 (3.5) 3.55 (±1.04)
 Stage 3 (advanced) 22 (2.4) 2.85 (±1.47)
 Stage 4 (severe) 20 (2.2) 2.80 (±1.73)
Severity of glaucoma in the better eye 0.0036¶
 No glaucoma or ocular hypertension 809 (88.3) 3.70 (±0.99)
 Stage 1 (mild) 69 (7.5) 3.41 (±1.09)
 Stage 2 (moderate) 25 (2.7) 3.26 (±1.51)
 Stage 3–Stage 4 (advanced to severe) 13 (1.4) 3.07 (±1.21)
Glaucoma subtypes 0.0002||
 No glaucoma or ocular hypertension 805 (86.7) 3.70 (±0.99)
 Non-POAG (primary angle closure glaucoma, pseudoexfoliative glaucoma) 33 (3.6) 3.26 (±1.40)
 POAG 90 (9.7) 3.28 (±1.29)
Table 4. 
 
Difference in Overall VF Score in Glaucoma in 3 Multivariate Linear Regression Models
Table 4. 
 
Difference in Overall VF Score in Glaucoma in 3 Multivariate Linear Regression Models
Model 1* Coefficient (95% CI) Model 2† Coefficient (95% CI) Model 3‡ Coefficient (95% CI)
Glaucoma laterality
 Normal 3.66 (1.00) 3.66 (0.99) 3.66 (0.99)
 Unilateral§ −0.29 (−0.54, −0.04) −0.29 (−0.53, −0.04) −0.29 (−0.53, −0.04)
 Bilateral −0.20 (−0.57, 0.16) −0.27 (−0.62, 0.09) −0.27 (−0.62, 0.09)
Severity of glaucoma (worse eye)
 No glaucoma/OHT – Stage 0 3.69 (1.00) 3.71 (0.96) 3.71 (0.96)
 Stage 1 −0.24 (−0.55, 0.07) −0.19 (−0.50, 0.13) −0.19 (−0.50, 0.13)
 Stage 2 0.03 (−0.35, 0.41) −0.04 (−0.41, 0.34) −0.04 (−0.41, 0.34)
 Stage 3 and Stage 4§ −0.65 (−1.03, −0.28) −0.51 (−0.90, −0.11) −0.51 (−0.90, −0.11)
Severity of glaucoma (better eye)
 No glaucoma/OHT – Stage 0 3.70 (0.99) 3.70 (0.98) 3.70 (0.98)
 Stage 1 −0.22 (−0.48, 0.04) −0.27 (−0.53, −0.006) −0.27 (−0.53, −0.006)
 Stage 2 −0.25 (−0.71, 0.21) −0.27 (−0.73, 0.19) −0.27 (−0.73, 0.19)
 Stage 3 and Stage 4 −0.40 (−1.00, 0.20) −0.41 (−1.03, 0.22) −0.41 (−1.03, 0.22)
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