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Topic Visual impairment (VI) and cognitive impairment (CIM) are prevalent age-related conditions that impose substantial burden on the society. Findings on the hypothesized bidirectional association of VI and CIM remains equivocal. Hence, we conducted a systematic review and meta-analysis to examine this bidirectional relationship. Clinical Relevance Sixty percent risk of CIM has not been well elucidated in the literature. A bidirectional relationship between VI and CIM may support the development of strategies for early detection and management of risk factors for both conditions in older people. Methods PubMed, Embase, and Cochrane Central registers were searched systematically for observational studies, published from inception until April 6, 2020, in adults 40 years of age or older reporting objectively measured VI and CIM assessment using clinically validated cognitive screening tests or diagnostic evaluation. Meta-analyses on cross-sectional and longitudinal associations between VI and CIM outcomes (any CIM assessed using screening tests and clinically diagnosed dementia) were examined. Random effect models were used to generate pooled odds ratios (ORs) and 95% confidence intervals (CIs). We also examined study quality, publication bias, and heterogeneity. Results Forty studies were included (n = 47 913 570). Meta-analyses confirmed that persons with VI were more likely to have CIM, with significantly higher odds of: (1) any CIM (cross-sectional: OR, 2.38 [95% CI, 1.84–3.07]; longitudinal: OR, 1.66 [95% CI, 1.46–1.89]) and (2) clinically diagnosed dementia (cross-sectional: OR, 2.43 [95% CI, 1.48–4.01]; longitudinal: OR, 2.09 [95% CI, 1.37–3.21]) compared with persons without VI. Significant heterogeneity was explained partially by differences in age, sex, and follow-up duration. Also, some evidence suggested that individuals with CIM, relative to cognitively intact persons, were more likely to have VI, with most articles (8/9 [89%]) reporting significantly positive associations; however, meta-analyses on this association could not be conducted because of insufficient data. Discussion Overall, our work suggests that VI is a risk factor of CIM, although further work is needed to confirm the association of CIM as a risk factor for VI. Strategies for early detection and management of both conditions in older people may minimize individual clinical and public health consequences.

PURPOSE To evaluate associations between choroidal thickness and features of polypoidal choroidal vasculopathy (PCV) lesions based on multimodal imaging. METHODS This cross-sectional analysis included treatment-naive PCV eyes from a prospectively recruited observational cohort. Associations between of subfoveal choroidal thickness (SFCT) and qualitative and quantitative morphologic features of PCV lesions on color fundus photographs, indocyanine green and fluorescein angiography, and spectral-domain optical coherence tomography were evaluated. RESULTS We included 100 eyes with indocyanine green angiography-proven PCV. Subfoveal choroidal thickness showed a bimodal distribution with peaks at 170 µm and 350 µm. There was a significant linear increase in the total lesion area (P-trend = 0.028) and the polypoidal lesion area (P-trend = 0.030 and P-continuous = 0.037) with increasing SFCT. Pairwise comparisons between quartiles showed that the total lesion area (4.20 ± 2.61 vs. 2.89 ± 1.43 mm2, P = 0.024) and the polypoidal lesion area (1.03 ± 1.01 vs. 0.59 ± 0.45 mm2, P = 0.042) are significantly larger in eyes in Q4 (SFCT ≥ 350 μm) than eyes in Q1 (SFCT ≤ 170 μm). Although there was no significant linear trend relating SFCT to best-corrected visual acuity, pairwise comparisons showed that eyes in Q4 (SFCT ≥ 350 μm) have significantly worse vision (0.85 ± 0.63 vs. 0.55 ± 0.27 logMAR, P = 0.030) than eyes in Q2 (SFCT 170-260 μm). CONCLUSION Total lesion areas and polypoidal lesion areas tend to be larger in eyes with increasing SFCT. Choroidal background may influence the phenotype or progression pattern of PCV.

Background/aimsTo examine the relationship between macular perfusion, as assessed using optical coherence tomography angiography (OCTA), and long-term visual outcome after surgical repair of macula-off rhegmatogenous retinal detachment (RRD).MethodsA prospective study of 29 patients who had undergone successful surgical repair of macula-off RRD. OCTA imaging was performed at month 3 and repeated at months 6 and 12 after surgery. Associations between OCTA parameters including, foveal avascular zone (FAZ) area, vessel density (VD) in the superficial capillary plexus (SCP) and deep capillary plexus (DCP), choriocapillaris flow deficit features and logMAR best-corrected visual acuity (VA) were assessed using a random intercept hybrid linear mixed model.ResultsOver the 1-year follow-up, VA improved (0.025 logMAR/ month, 95% CI 0.015 to 0.035) and FAZ area decreased (−0.020 mm2/month, 95% CI −0.032 to −0.007). Better VA after surgery was significantly associated with denser superficial VD (β=0.079, 95% CI 0.026 to 0.131), lower number of choriocapillaris flow deficits (β=−0.087, 95% CI −0.154 to −0.021) and larger average size of choriocapillaris flow deficits (β=0.085, 95% CI 0.022 to 0.147), after adjusting for baseline VA, types of surgery and other factors.ConclusionsOCTA measures of vascular perfusion in the macula may provide new pathophysiological insights and prognostic information related to macula-off RRD.

Purpose Visual impairment (VI) can have a detrimental impact on vision-related quality of life (VRQoL), but it is still unclear how this relationship varies with age across the VI spectrum. We determined the age-stratified, cross-sectional, and longitudinal associations between VI severity and VRQoL. Design The baseline and follow-up Singapore Chinese Eye Studies (SCES-1/-2; 2009–2011 and 2015–2017). Participants A total of 3068 SCES-1 participants (mean age [standard deviation {SD}]: 59.5 [9.8] years; 50.2% female) and 1919 SCES-2 participants (mean age [SD]: 56.8 [8.3] years; 49.9% female). Methods Visual impairment was defined as visual acuity (VA) of > 0.3 logarithm of the minimum angle of resolution (logMAR) units; VI severity as mild-moderate (logMAR scores less than the median of all individuals with VI) and severe (logMAR scores median or greater); and VI incidence as VI absence at baseline, but evident at follow-up. Age was stratified into 40 to 49 years, 50 to 64 years, and ≥65 years. Main Outcome Measures Rasch-transformed scores from the 32-item Impact of Visual Impairment (IVI) questionnaire were used to measure the “Reading,” “Mobility,” and “Emotional” domains of VRQoL. Multiple linear regression models determined the age-stratified associations of prevalent and incident VI with all 3 VRQoL outcomes, adjusted for potential confounders. Results Of the 807 persons with prevalent VI, 55.9% had mild-moderate and 44.1% had severe VI. Compared with no VI, age-stratified analyses showed that VRQoL decrements were significant only in the older age groups (mild-moderate VI: 6.2% and 8.1% reduction in Mobility and Reading scores in those aged ≥ 65 years; severe VI: 8.5% to 13.4% reductions in the 3 VRQoL scores in those aged ≥ 50 years). This interaction with older age became more pronounced with incident VI (N = 168), where decrements in all 3 VRQoL domains were evident only in those aged ≥65 years compared with persons without incident VI. Conclusions Our results suggest that the VI-VRQoL associations are driven mainly by older individuals aged ≥65 years, highlighting the need for effective regular screening and early intervention modalities to prevent the presence and onset of VI, and subsequent VRQoL declines, in these individuals.

Background The relationship between self-reported visual disability and cognitive impairment in older individuals is unclear. Objective To determine the relationship of vision-specific functioning (VSF), vision-specific mobility (VSM) and visual acuity (VA) with clinically assessed cognitive impairment in the Epidemiology of Dementia in Singapore study. Design Cross-sectional. Setting Population-based. Subjects Eight hundred and seventy-four adults aged ≥60 years at higher risk of possible cognitive impairment by the Abbreviated Mental Test and progressive forgetfulness question. Methods VSF and VSM were measured using Rasch-transformed continuous scores of two Impact of Vision Impairment questionnaire domains. Cognitive impairment was objectively determined using detailed neuropsychological testing and defined as no cognitive impairment (NCI), mild cognitive impairment-no dementia (CIND), moderate CIND only and moderate CIND or dementia. Associations were assessed using multinomial logistic regression models. Results Of the 874 participants (49.0% males, mean age (SD) 65.5 (7.0) years), 277, 281 and 316 had NCI, mild CIND and moderate CIND or dementia, respectively. Compared to NCI, the odds of moderate CIND, and moderate CIND or dementia increased for every SD worsening in VSF (OR: 1.44, 95% CI 1.14–1.82, and OR: 1.52, 95%CI 1.19–1.94, respectively) and VSM (OR: 1.42, 95%CI 1.11–1.81, and OR: 1.50, 95%CI 1.15–1.95). Similarly, the odds of mild CIND (OR: 1.62, 95%CI 1.19–2.22), moderate CIND (OR: 1.93, 95%CI 1.45–2.58), and moderate CIND or dementia (OR: 2.25, 95%CI 1.62–3.11) increased significantly with every SD worsening of VA. Conclusions Our results emphasise the importance of interventions to prevent vision loss and improve quality of life to reduce likelihood of age-related cognitive decline.

Purpose To assess the impact of delaying anti–vascular endothelial growth factor (VEGF) treatment of active disease at any point during a patient’s treatment journey on clinical outcomes in a real-world cohort of patients with neovascular age-related macular degeneration (nAMD). Design Longitudinal cohort study. Participants Consecutive treatment-naive nAMD eyes commencing anti-VEGF monotherapy (bevacizumab, ranibizumab, or aflibercept) from January 2014 from a tertiary eye center in Singapore. Methods We conducted a real-world study using registry data comparing delayed re-treatment (defined as not receiving treatment at 2 or more monitoring visits when disease was graded as active) versus timely re-treatment (defined as receiving treatment when disease was active). Main Outcome Measures The primary outcome was the change in visual acuity (VA) in the timely and delayed re-treatment groups at 12 months. Results Data from 286 eyes were included and categorized into the timely (188 [66%]) or the delayed (98 ([34%]) group. The mean numbers of anti-VEGF injections over 12 months were similar: 5.6 (standard deviation [SD], 2.9) versus 4.9 (SD, 3.2; P = 0.11) for the timely and delayed groups, respectively. Timely treated patients showed larger gains in VA (6.4 letters [SD, 8.1 letters] vs. 1.2 letters [SD, 5.3 letters; P = 0.04), a higher proportion with VA of 6/12 or better (30% vs. 8%; P = 0.01), and greater reduction in OCT-measured central subfield thickness (135 μm [SD, 154 μm] vs. 87.8 μm [SD, 129 μm]; P = 0.04) at 12 months. A longer delay between detection of active disease and re-treatment was associated with poorer vision outcomes (0.02-letter decrease/day; P = 0.03; R2 = 0.29). Conclusions Although it has been established that adequate numbers of injections are required for favorable outcomes, timely re-treatment of active disease also is important. This should be emphasized to patients to ensure optimal outcomes in real-world clinical settings.

Although the impact of vision-related quality of life (VRQoL) is assessed optimally using binocular visual acuity (VA), uniocular VA remains the preferred measurement method in clinic-based and epidemiologic studies. We compared the impact of distance presenting binocular VA and uniocular VA in the better-seeing (better-eye VA) and worse-seeing (worse-eye VA) eye on VRQoL.The Singapore Chinese Eye Study 2 (2015-2017), a population-based, cross-sectional study.One thousand eight hundred twenty-two individuals (mean age, 66.2 years [standard deviation, 8.9 years]; 51.1% women) were included.Presenting uniocular VA and binocular VA were assessed using a logarithm of the minimum angle of resolution number chart at a distance of 4 m under standard lighting by trained and certified study optometrists. Multiple linear regression models were constructed to determine the independent associations between binocular VA, better-eye VA, and worse-eye VA and the outcome (VRQoL), adjusted for potential confounders, including age, gender, socioeconomic status, and presence of comorbidities. In addition, a cluster sandwich estimator was used to determine if any differences in β estimates between the associations were statistically significant.Vision-related quality of life was measured using Rasch-transformed scores from the emotional, mobility, and reading domains of the Impact of Visual Impairment (IVI) questionnaire.Although every 2-line increase (worsening) in binocular VA and uniocular VA was associated independently with decrements in emotional, mobility, and reading IVI scores (P0.05 for all), the reductions in all VRQoL domains were substantially lower (P0.1) when using either the better-eye VA (compared with binocular VA β-estimates, -27.8%, -19.4%, and -24.2% difference in emotional, mobility, and reading IVI scores, respectively) or worse-eye VA (compared with binocular VA β estimates, -38.9%, -58.1%, and -57.5% reduction in emotional, mobility, and reading IVI scores, respectively) to quantify vision loss.Uniocular VA seems to underestimate the impact of vision loss on VRQoL indices compared with binocular VA. Our data suggest that researchers, clinicians, and policy planners should consider using binocular instead of uniocular measures of VA in patient-reported outcome evaluation of vision loss because it may better reflect its impact on VRQoL.

Purpose The aim of this study was to determine whether cataract surgery was associated with age-related macular degeneration (AMD) development in Asian patients. Design Longitudinal cohort study. Methods Participants from the Singapore Malay and Indian Eye Studies were recruited between 2004 and 2015. A total of 6790 late-AMD-free eyes from 3475 individuals were followed for 6 years on average. Multivariable regression analysis using generalized estimating equations determined associations between cataract surgery and the incidence of any, early, and late AMD. Results The mean age (SD) of participants was 55.5 (9.1) years; 48.1% were male; 11.3% of eyes had cataract surgery recorded; incident any, early, and late AMD developed in 238 (3.6%), 222 (3.4%), and 29 (0.4%) eyes, respectively. Operated eyes had higher incidence of late AMD [1.4% vs 0.3%; adjusted risk ratio (RR): 3.47, 95% confidence interval (CI) 1.40-8.57], but not early AMD (6.0% vs 3.0%, adjusted RR: 1.12, 95% CI 0.76-1.64) or any AMD (6.9 vs 3.2%, adjusted RR: 1.23, 95% CI 0.85-1.78). Conclusions Our data are consistent with findings in population-based Caucasian studies that cataract surgery may be associated with incidence of late AMD. However, the absolute risk of late AMD development remains low and physicians should continue to balance the benefits and risks of cataract surgery in elderly patients.

To describe the rationale, design and methodology of a geographically-representative and population-based study investigating the epidemiology, impact, personal and economic burden of age-related eye diseases, declining visual and other sensory systems in Asians aged >60 years in Singapore.PIONEER (The PopulatION HEalth and Eye Disease PRofilE in Elderly Singaporeans Study) is currently a cross-sectional study targeting 3152 Chinese, Malay and Indian adults who are Singapore citizens or permanent residents aged 60 years and older living across Singapore. The study is intended to be longitudinal, with several waves of data planned to be collected in the future. The sampling frame consisted of 7000 names derived from age, gender and ethnicity-stratified random sampling of individuals >60 years. Selected individuals were invited via letters, home visits, and telephone calls for a clinical assessment at the Singapore Eye Research Institute. Individuals with limited mobility were examined in a custom-designed mobile eye clinic. Questionnaires were subsequently administered at participants' homes by trained interviewers in their preferred language. A total of 3,299 participants (from East, West, North and South Singapore) were approached from December 2017 to November 2019. Of these, 953 (28.5%) were deemed ineligible. Out of 2,346 eligible participants, 904 (38.5%) refused, and 1,442 (61.5%) attended our clinical testing protocol, giving an initial response rate of 61.5%. Of these, 1,170 (81%) were cognitively able to complete the questionnaire assessment. The mean age±SD of our participants was 73.8±8.6 years; n=798 (55.3%) were female; and 828 (57.4%) were of Chinese ethnicity. The findings from this study will allow a deeper understanding of the risk factors and impact of aging in Asian populations, particularly in relation to the visual function and other functional system.

Purpose We sought to determine the association of refractive error and its associated determinants (axial length [AL], anterior chamber depth, and corneal curvature) with the incidence and progression of diabetic retinopathy (DR). Design Population-based cohort study. Methods A total of 1562 eyes of 840 individuals with diabetes and gradable retinal photographs (mean age [SD], 57.0 [8.3] years, 48.2% female) from the Singapore Malay and Indian Eye Studies at baseline (2004–2009) and follow-up (2011–2015) examinations were included in the analyses. Refractive error was calculated as sphere plus half negative cylinder, while AL, anterior chamber depth, and corneal curvature were assessed using optical biometry. Incident DR was defined as having no baseline DR and any DR at follow-up; incident vision-threatening DR as no baseline vision-threatening DR but present at follow-up; and DR progression as an increase in severity at follow-up from at least minimal baseline DR. Eye-specific data and generalized estimating equation models were used to account for between-eye correlation to determine the relationships between the exposures and outcomes, adjusted for traditional DR risk factors. Results At follow-up, 164 of 1273 (12.9%) eyes had incident DR, 17 of 1542 (1.1%) eyes had incident vision-threatening DR, and 75 of 269 (27.9%) eyes with baseline DR experienced progression. A longer AL (per millimeter increase) (risk ratio 0.58 [95% confidence interval 0.38–0.88) was associated with a lower risk of incident DR. No other associations were found. Conclusion Our findings show that a longer AL is protective of incident DR.

Introduction: We investigated knowledge, attitudes, and practice (KAP) about COVID-19 and related preventive measures in Singaporeans aged > 60 years. Methods: This was a population-based, cross-sectional, mixed-methods study (13 May 2020–9 June 2020) of participants aged >60 years. Self-reported KAP about ten COVID-19 symptoms and six government-endorsed preventive measures were evaluated. Multivariable regression models identified sociodemographic and health-related factors associated with knowledge, attitudes and practices in our sample. Associations between knowledge/attitude scores, and practice categories were determined using logistic regression. 78 participants were interviewed qualitatively about practice of additional preventive measures and data were analysed thematically. Results: Mean awareness score of the symptoms was 7.2/10. Fever (93.0%) and diarrhoea (33.5%) were the most- and least-known symptoms, respectively. Most knew all six preventive measures (90.4%), perceived them as effective (78.7%), and practiced ‘wear a mask’ (97.2%). Indians, Malays, and those in smaller housing had poorer mean knowledge of COVID-19 symptoms scores. Older participants had poorer attitudes towards preventive measures. Compared to Chinese, Indians had lower odds of practicing 3/6 recommendations. A one-point increase in knowledge of and attitudes towards preventive measures score had higher odds of always practicing 3/6 and 2/6 measures, respectively. Qualitative interviews revealed use of other preventive measures, e.g. maintaining a healthy lifestyle. Conclusions: Elderly Singaporeans displayed high levels of KAP about COVID-19 and related preventive measures, with a positive association between levels of knowledge/attitude, and practice. However, important ethnic and socioeconomic disparities were evident, suggesting key vulnerabilities remain, requiring immediate attention.

To evaluate whether optical coherence tomography (OCT) can determine polypoidal lesion (PL) perfusion in polypoidal choroidal vasculopathy eyes after 12 months of aflibercept monotherapy. Polypoidal lesion perfusion status, assessed by indocyanine green angiography, is an important anatomical outcome in polypoidal choroidal vasculopathy management.Post hoc data from a prospective randomized, open-label, study in eyes with polypoidal choroidal vasculopathy undergoing monotherapy with aflibercept evaluated PL perfusion status based on indocyanine green angiography (gold standard) and OCT features from baseline to 12 months.Individual PLs (110 in total) from 48 eyes (48 patients) showed at 12 months; 57/110 PLs (51.8%) were closed on indocyanine green angiography. At 12 months, eyes with closed PLs were more likely to have the following OCT features: 1) no subretinal fluid (67.1% vs. 32.9%), 2) smaller pigment epithelial detachment height (67.2 [±43.8] vs. 189.2 [±104.9] μm), 3) densely hyperreflective pigment epithelial detachment contents (84.0% vs. 16.0%), 4) an absence of a hyperreflective ring(64.0% vs. 36.0%), and a 5) indistinct overlying retinal pigment epithelial (71.4% vs. 28.6%) (all P0.05). The three highest performing OCT features that differentiated perfused from closed PLs were (1), (3), and (4) (area under the receiver operating characteristic curve 0.85, 0.73, and 0.70, respectively). A combination of these three features achieved an area under the receiver operating characteristic curve of 0.90.Polypoidal lesion closure, an important anatomical treatment outcome in polypoidal choroidal vasculopathy typically defined by indocyanine green angiography, can be accurately detected by specific OCT features.

IMPORTANCE: A glaucoma-specific instrument for estimating utilities across the spectrum of glaucoma severity is currently lacking, hindering the assessment of the cost-effectiveness of glaucoma treatments. OBJECTIVE: To develop and validate the preference-based Glaucoma Utility Instrument (Glau-U) and to ascertain the association between Glau-U utilities and severity of glaucoma and vision impairment. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study was conducted in 2 stages at the Singapore National Eye Centre glaucoma clinics. Stage 1 focused on the identification and pretesting of the Glau-U attributes and was carried out between June 2009 and May 2016. Stage 2 involved the development and administration of the discrete choice experiment (DCE) survey and tasks and was conducted between May 7, 2018, and December 11, 2019. Stage 2 participants were English- or Mandarin-speaking Singaporean citizens or permanent residents of Chinese, Malay, or Indian ethnicity who were 40 years or older and had a clinical diagnosis of glaucoma in at least 1 eye. EXPOSURES: Glau-U comprised 6 quality-of-life attributes: activities of daily living, lighting and glare, movement, eye discomfort, other effects of glaucoma, and social and emotional effects. The descriptions or response options for these attributes were no difficulty or never, some difficulty or sometimes, or severe difficulty or often. MAIN OUTCOMES AND MEASURES: Utility weights for Glau-U were developed using a DCE questionnaire, which was interviewer administered to participants. Mixed logit regression determined utility weights for each health state. Glau-U utility weights across better- or worse-eye glaucoma and vision impairment severity were calculated using 1-way analysis of variance. Correlations between Glau-U utilities and better- or worse-eye visual fields and EuroQol 5-Dimension utilities were ascertained to assess convergent and divergent validity. RESULTS: Of the 304 participants (mean [SD] age, 68.3 [8.7] years; 182 men [59.9%]), 281 (92.4%) had no vision impairment in the better eye, 13 (4.3%) had mild impairment, and 10 (3.3%) had moderate to severe vision impairment. Mean (SD) Glau-U utilities decreased as better-eye glaucoma severity increased (none: 0.73 [0.21]; mild: 0.66 [0.21]; moderate: 0.66 [0.20]; severe: 0.60 [0.28]; and advanced or end-stage: 0.22 [0.38]; P

Background/AimsTo determine if selective laser trabeculoplasty (SLT) is superior to topical medication as a first-line treatment for glaucoma on quality of life (QoL) and clinical outcomes.MethodsIn this international, longitudinal, multisite randomised controlled trial, treatment naïve mild-to-moderate primary open angle or exfoliation glaucoma patients were randomised 1:1 to SLT or topical medication. Glaucoma-specific QoL (primary outcome) was measured using the Glaucoma Outcomes Assessment Tool (GOAT; 342 items, 12 domains). Secondary outcomes included rate of successful intraocular pressure (IOP) reduction (>25% reduction from baseline) and presence of ocular surface disease including conjunctival hyperaemia and eyelid erythema. Our intention-to-treat analysis was performed at months 12 and 24.ResultsOf 167 enrolled patients, 83 and 84 were randomised to SLT and topical medication, respectively; and 145 (n=75 SLT, n=70 medication) completed 24-month follow-up. While both treatment arms achieved significant within-group gains in GOAT outcomes at both endpoints, SLT patients reported a greater between-group improvement in ‘social well-being’ compared with medication patients (mean±SE=0.28±0.13; p=0.034) at 24 months. At month 24, the rate of successful IOP reduction was 18.6% (95% CI 3.0% to 34.3%, p=0.022) higher (absolute difference) in the medication compared with SLT group. More individuals in the medication group had conjunctival hyperaemia and eyelid erythema compared with SLT at 24 months.ConclusionOverall, we did not find evidence that SLT was superior to medication in improving glaucoma-specific QoL. While we found superior IOP reduction in the medication arm, eyelid erythema and conjunctival hyperaemia were more prevalent in these patients compared with the SLT group.Trial registrationACTRN12611000720910.

The association between objective measures of body composition (BC) with type 2 diabetes (T2DM) is inconclusive. We conducted a systematic review and meta-analysis to examine the association between several body composition (BC) indices assessed using dual energy X-ray absorptiometry (DXA), and T2DM. Using PRISMA guidelines, we searched for observational studies investigating BC measures, including total body fat mass (BFM), visceral fat mass (VFM), subcutaneous fat mass (SFM), and fat free mass (FFM); and T2DM. Of 670 titles initially identified, 20 were included. High VFM was consistently associated with T2DM. For every kg increase in VFM, the odds of having T2DM increased by two-fold for males (OR 2.28 [95% CI 1.42 to 3.65], p = 0.001) and more than 4-fold for females (OR 4.24 [1.64 to 11.02], p = 0.003). The presence of T2DM was associated with 2-fold higher odds of low FFM (OR 2.38 [1.44 to 3.95]). We found evidence that greater VFM is a risk factor for prevalent and incident T2DM. While the presence of T2DM is associated with reduced FFM; the relationship between FFM and BFM with T2DM remains unclear. Reducing VFM and increasing FFM through lifestyle changes may reduce the risk of T2DM and mitigate its deleterious effect on BC, respectively.

Purpose: To investigate the prevalence of dual sensory impairment (DSI), its associated factors and relationship with health-related quality of life (HR-QoL) in residential care facilities (RCF) in Singapore.Methods: This was a cross-sectional study of 123 residents aged ≥40 years from six RCFs, conducted between 2016 and 2018. DSI was defined as concomitant presenting visual acuity (better-eye) >0.3 logarithm of the minimum angle of resolution and a pure-tone air conduction threshold (better-ear) >40 dB HL in any of the four tested frequencies (500, 1000, 2000 and 4000 Hz). HR-QoL was quantified using the EuroQol five-dimension questionnaire. Multivariable Poisson regression was used to determine the associated factors of DSI. Multivariable linear regression was used to determine the association between DSI and HR-QoL adjusted for traditional confounders.Results: Of the 123 residents (age [mean±standard deviation] 75.3 ± 10.8 years; 56.9% male), 97 (78.9%[95% confidence interval(CI):71.6%, 86.1%]) had DSI, with 110 (98.2%) not on follow-up care for their sensory disabilities. In multivariable models, male gender (prevalence ratio(PR) [95%CI] = 1.3[1.1, 1.6]), older age (per 10-year increase (1.2[1.1, 1.3])), education ≤6 years (1.3[1.1, 1.7]) and the presence of cataract (1.3[1.0, 1.7]) were independently associated with DSI. DSI was independently associated with a substantial worsening in HR-QoL (β = -0.61; 95%CI: -0.76, -0.45; p < .001).Conclusions: DSI affects four in five residential care residents and is substantially associated with reductions in HR-QoL in these residents. Our finding highlights an urgent need for the implementation of routine vision and hearing screening and follow-up care for residents living in these facilities.

AimsTo examine the relationship between vision impairment (VI) and employment outcomes in a multiethnic Asian population.MethodsWe included 7608 Asian individuals aged ≥40 years (mean (SD) age: 58.4 (10.3) years; 64.8% male) from the Singapore Epidemiology Eye Disease Study (response rate: 78.8%), a population-based cohort study (mean follow-up period: 6.2 years). Presenting visual acuity (VA) was assessed using a logarithm of the minimum angle of resolution (logMAR) chart, with VI defined as mild (VA >0.3 to ResultsPresenting VI was prevalent in 20.2% (N=1536) of participants. Compared with those without VI, participants with mild and moderate to severe VI were more likely to be unemployed at baseline (OR 1.47, 95% CI 1.15 to 1.87, p=0.002 and 2.74, 95% CI 1.94 to 3.89, pConclusionVI, even when mild, is associated with unemployment and underemployment. Future studies should investigate whether visual interventions could be used as part of a multipronged strategy to improve employment outcomes for the population.

Background Age-related sensory loss and frailty are common conditions among older adults, but epidemiologic research on their possible links has been inconclusive. Clarifying this relationship is important because sensory loss may be a clinically relevant risk factor for frailty. Methods In this systematic review and meta-analysis, we searched 3 databases for observational studies investigating 4 sensory impairments—vision (VI), hearing (HI), smell (SI), and taste (TI)—and their relationships with frailty. We meta-analyzed the cross-sectional associations of VI/HI each with pre-frailty and frailty, investigated sources of heterogeneity using meta-regression and subgroup analyses, and assessed publication bias using Egger’s test. Results We included 17 cross-sectional and 7 longitudinal studies in our review (N = 34,085) from 766 records. Our cross-sectional meta-analyses found that HI and VI were, respectively, associated with 1.5- to 2-fold greater odds of pre-frailty and 2.5- to 3-fold greater odds of frailty. Our results remained largely unchanged after subgroup analyses and meta-regression, though the association between HI and pre-frailty was no longer significant in 2 subgroups which lacked sufficient studies. We did not detect publication bias. Longitudinal studies largely found positive associations between VI/HI and frailty progression from baseline robustness, though they were inconclusive about frailty progression from baseline pre-frailty. Sparse literature and heterogenous methods precluded meta-analyses and conclusions on the SI/TI–frailty relationships. Conclusions Our meta-analyses demonstrate significant cross-sectional associations between VI/HI with pre-frailty and frailty. Our review also highlights knowledge gaps on the directionality and modifiability of these relationships and the impact of SI/TI and multiple sensory impairments on frailty.

Purpose A validated questionnaire assessing diabetic retinopathy (DR)- and diabetic macular edema (DME)-related knowledge (K) and attitudes (A) is lacking. We developed and validated the Diabetic Retinopathy Knowledge and Attitudes (DRKA) questionnaire and explored the association between K and A and the self-reported difficulty accessing DR-related information (hereafter referred to as Access). Methods In this mixed-methods study, eight focus groups with 36 people with DR or DME (mean age, 60.1 ± 8.0 years; 53% male) were conducted to develop content (phase 1). In phase 2, we conducted 10 cognitive interviews to refine item phrasing. In phase 3, we administered 28-item K and nine-item A pilot questionnaires to 200 purposively recruited DR/DME patients (mean age, 59.0 ± 10.6 years; 59% male). The psychometric properties of DRKA were assessed using Rasch and classical methods. The association between K and A and DR-related Access was assessed using univariable linear regression of mean K/A scores against Access. Results Following Rasch-guided amendments, the final 22-item K and nine-item A scales demonstrated adequate psychometric properties, although precision remained borderline. The scales displayed excellent discriminant validity, with K/A scores increasing as education level increased. Compared to those with low scores, those with high K/A scores were more likely to report better access to DR-related information, with K scores of 0.99 ± 0.86 for no difficulty; 0.79 ± 1.05 for a little difficulty; and 0.24 ± 0.85 for moderate or worse difficulty (P Conclusions The psychometrically robust 31-item DRKA questionnaire can measure DR- and DME-related knowledge and attitudes. Translational relevance The DRKA questionnaire may be useful for interventions to improve DR-related knowledge and attitudes and, in turn, optimize health behaviors and health literacy.

Purpose To evaluate the change of retinal thickness and ocular microvasculature in a rat model of retinitis pigmentosa using swept source optical coherence tomography angiography (SS-OCTA). Methods Three-weeks-old Royal College of Surgeons (RCS) rats (n = 8) and age-matched control rats (n = 14) were imaged by a prototype SS-OCTA system. Follow-up measurements occurred every three weeks on six RCS rats until week 18, and cross-sectional measurements were conducted on control rats. Thicknesses of different retinal layers and the total retina were measured. The enface angiograms from superficial vascular plexiform (SVP) and deep capillary plexiform (DCP) were analyzed, and the image sharpness was also extracted from the choroidal angiograms. Immunohistochemical analysis was done in the RCS rats after week 18, as well as in three-week-old RCS rats and age-matched controls. Results In RCS rats, the thicknesses of the ganglion cell complex, the nuclear layer, the debris/photoreceptor layer and the total retina decreased over the weeks (P < 0.001). The SVP metrics remained unchanged whereas the DCP metrics decreased significantly over the weeks (P < 0.001). The immunohistochemical analysis confirmed our OCTA findings of capillary dropout in the DCP. The choroidal plexus appeared indistinct initially due to scattering of light at the intact retinal pigment epithelium (RPE) and became more visible after week nine probably due to RPE degeneration. Loss of choriocapillaris was visualized at week 18. In control rats, no vascular change was detected, but nuclear layers, photoreceptor layers and total retina showed slight thinning with age (P < 0.001). Conclusions Photoreceptor degeneration in RCS rats was associated with the loss of capillaries in DCP, but not in SVP. The OCTA imaging allows for the characterization of structural and angiographic changes in rodent models.

Purpose We examined the longitudinal association of baseline alcohol intake and frequency with the 6-year incidence and progression of diabetic retinopathy (DR) in a population-based cohort of Singaporean Indians. Methods We included 656 participants with diabetes mellitus, gradable retinal photographs from baseline (2007–2009) and follow-up (2013–2015) examinations, information on alcohol intake and other relevant data from the Singapore Indian Eye Study were included. Incident DR was defined using the Modified Airlie House Classification as no DR at baseline and at least minimal non-proliferative DR at follow-up; and DR progression as at least a one-step worsening in DR at follow-up from minimal or worse status at baseline, excluding those with proliferative DR. Results The mean age (SD) of our participants (n=656) was 58.8 (9.2) years, and 54.4% were male. At follow-up, 82 of 510 (16%) participants developed DR, and 45 of 146 (30.8%) had DR progression. 65 (12.7%) and 28 (19.1%) participants consumed alcohol in incident DR and progression categories, respectively. In multivariable analyses, those who consumed alcohol had nearly two-thirds reduced odds of incident DR (OR (95% CI): 0.36 (0.13 to 0.98)) compared with those who did not. Participants with infrequent consumption of alcohol also had a reduction in odds of incident DR (0.17 (0.04 to 0.69)), compared with non-drinkers. No association was found between alcohol consumption and DR progression. Conclusions and relevance In our longitudinal population of Singapore Indians, baseline alcohol intake, particularly infrequent consumption, was associated with lower risk of developing DR, compared with non-drinkers, in line with previous cross-sectional findings.

Background/aimsTo validate a preference-based Diabetic Retinopathy Utility Index (DRU-I) using discrete choice experiment (DCE) methods and assess disutilities associated with vision-threatening DR (VTDR: severe non-proliferative DR, proliferative DR and clinically significant macular oedema) and associated vision impairment.MethodsThe DRU-I comprises five quality-of-life dimensions, including Visual symptoms, Activity limitation/mobility, Lighting and glare, Socio-emotional well-being and Inconvenience, each rated as no, some, or a lot of difficulty. The DRU-I was developed using a DCE comprising six blocks of nine choice sets which, alongside the EuroQoL-5D (EQ-5D-3L) and Vision and Quality of Life (VisQoL) utility instruments, were interviewer-administered to participants. To ensure the DRU-I was sensitive to severe disease, we oversampled patients with VTDR. Data were analysed using conditional logit regression.ResultsOf the 220 participants (mean±SD age 60.1±11.3 years; 70.9% men), 57 (29.1%) and 139 (70.9%) had non-VTDR and VTDR, respectively, while 157 (71.4%), 20 (9.4%) and 37 (17.3%) had no, mild or moderate/severe vision impairment, respectively. Regression coefficients for all dimensions were ordered as expected, with worsening levels in each dimension being less preferred (theoretical validity). DRU-I utilities decreased as DR severity (non-VTDR=0.87; VTDR=0.80; p=0.021) and better eye vision impairment (none=0.84; mild=0.78; moderate/severe=0.72; p=0.012) increased. DRU-I utilities had low (r=0.39) and moderate (r=0.58) correlation with EQ-5D and VisQoL utilities, respectively (convergent validity).DiscussionThe DRU-I can estimate utilities associated with vision-threatening DR and associated vision impairment. It has the potential to assess the cost-effectiveness of DR interventions from a patient perspective and inform policies on resource allocation relating to DR.

PurposeTo use optical coherence tomography angiography (OCTA) parameters from both the retinal and choroidal microvasculature to detect the presence and severity of diabetic retinopathy (DR).MethodThis is a cross-sectional case–control study. OCTA parameters from retinal vasculature, fovea avascular zone (FAZ) and choriocapillaris were evaluated from 3×3 mm2fovea-centred scans. Areas under the receiver operating characteristic (ROC) curve were used to compare the discriminative power on the presence of diabetes mellitus (DM), the presence of DR and need for referral: group 1 (no DM vs DM no DR), group 2 (no DR vs any DR) and group 3 (non-proliferative DR (NPDR) vs proliferative DR (PDR)).Results35 eyes from 27 participants with no DM and 132 eyes from 75 with DM were included. DR severity was classified into three groups: no DR group (62 eyes), NPDR (51 eyes), PDR (19 eyes). All retinal vascular parameters, FAZ parameters and choriocapillaris parameters were strongly altered with DR stages (pConclusionsEvaluating OCTA parameters from both the retinal and choroidal microvasculature in 3×3 mm scans improves the discrimination of DM and early DR.

Background/aimsTo assess the independent impact of diabetic retinopathy (DR) on three domains of vision-related quality of life (VRQoL) in a Chinese Singapore population.MethodsThe Singapore Chinese Eye Study (n=3353; 2009–2011) was a population-based, prospective, cross-sectional study conducted at the Singapore Eye Research Institute. The study population included 292 adults with diabetes, with and without DR. DR (better eye) was categorised as presence and absence of any DR; severity of DR (no vision-threatening DR (VTDR); severe non-proliferative DR (NPDR); PDR and/or clinically significant macular oedema and VTDR). Our main outcome was VRQoL which was measured using Rasch-calibrated scores from the ‘Reading’, ‘Mobility’ and ‘Emotional’ domains of the Impact of Vision Impairment questionnaire. The relationship between DR and VRQoL was assessed using multiple linear regression models.ResultsOf the 292 individuals (mean age 61.35 ± 9.66 years; 55.8% male), 201 (68.8%), 49 (16.8%), 20 (6.8%), 22 (7.5%) and 27 (9.2%) had no DR, minimal-mild NPDR, moderate-severe NPDR, PDR and VTDR, respectively. Any DR and VTDR were independently associated with 6% and 12% worse Reading scores and 7% and 18% poorer Emotional well-being, respectively, compared with those without DR. These associations persisted after separate adjustment for visual impairment and presenting visual acuity. No significant difference was found in the Mobility domain between persons with and without DR.ConclusionsWe documented that DR, particularly VTDR, was independently associated with restrictions in Reading and Emotional well-being. Understanding factors underlying the detrimental DR-VRQoL relationship may optimise rehabilitation outcomes for individuals with DR.

To examine the relationship between macular microvasculature parameters and functional changes in persons with diabetic retinopathy (DR).Cross-sectional study of 76 eyes with varying levels of DR. Optical coherence tomography angiography (OCTA) quantified superficial and deep perifoveal vessel densities and foveal avascular zone areas. Retinal sensitivity was measured using microperimetry. Optical coherence tomography angiography parameters and retinal sensitivity were correlated.Deep perifoveal vessel density decreased with increasing severity of DR (adjusted mean 51.93 vs. 49.89 vs. 47.96, P-trend = 0.005). Superficial and deep foveal avascular zone area increased with increasing DR severity (adjusted mean: 235.0 µm vs. 303.4 µm vs. 400.9 µm, P-trend = 0.003 [superficial]; 333.1 µm vs. 513.3 µm vs. 530.2 µm, P-trend = 0.001 [deep]). Retinal sensitivity decreased with increasing DR severity (adjusted mean: 25.12 dB vs. 22.34 dB vs. 20.67 dB, P-trend = 0.003). Retinal sensitivity correlated positively with deep perifoveal vessel density (Pearson's ρ = 0.276, P = 0.020) and inversely with superficial foveal avascular zone area (Pearson's ρ = -0.333, P = 0.010).Alterations in retinal microvasculature can be observed with OCTA with increasing severity of DR. These changes are correlated with reduced retinal sensitivity. Optical coherence tomography angiography is useful to detect and quantify the microvasculature properties of eyes with diabetic macular ischemia.

Background To explore the prevalence and determinants of unawareness of diabetes, hypertension and hypercholesterolemia and its association with poor disease control in a multi-ethnic Asian population without cardiovascular disease (CVD). Methods We included 6904 Chinese, Malay and Indian individuals (mean age [SD] 58.2 [10.2] years; 52.6% female) with diabetes, hypertension and/or hypercholesterolemia from the cross-sectional population-based Singapore Epidemiology of Eye Diseases study (2004–2011). Diabetes was defined as random blood glucose ≥ 11.1 mmol/L or HbA1c > 6.5% or self-reported use of diabetes medication; hypertension as systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg or self-reported use of anti-hypertensive treatment; and hypercholesterolemia as total cholesterol ≥ 6.2 mmol/L or self-reported use of lipid-lowering medications. Unawareness was based on participants’ answers to the questions: “Did your medical practitioner ever tell you that you have diabetes/hypertension/high cholesterol?” The determinants of unawareness, and its association with poor disease control, were assessed using multivariable binary logistic regression models adjusted for known potential confounders. Results Of the 2380 (34.5%), 5386 (78.0%) and 3607 (52.2%) with diabetes, hypertension and hypercholesterolemia, respectively, unawareness rates were 30.7%, 43.1% and 40.9%, respectively. Having a higher BMI, particularly if obese, and Malay ethnicity were associated with greater unawareness of diabetes; Malay and Indian ethnicities and current smoking with greater unawareness of hypertension; and education ≤6 years, current smoking, and blue collar jobs or unemployment with greater unawareness of hypercholesterolemia (all P < 0.05). Lack of awareness of each condition was independently associated with poorer disease control in the case of hypertension and hypercholesterolemia, while the converse was true for diabetes (all P < 0.05). Conclusions Unawareness of diabetes, hypertension, or hypercholesterolemia is high in Singapore, with risk factors varying across all three diseases, although Malay ethnicity is a consistent one. Unawareness was also associated with poor management for hypertension and hypercholesterolemia. Public health education and screening programs should target at-risk individuals, especially Malays, to reduce the likelihood of incident CVD.

Purpose To evaluate the prevalence and risk factors for diabetic retinopathy (DR) in the Singapore Epidemiology of Eye Diseases (SEED) Study. Design Population-based, cross-sectional study. Participants Persons of Malay, Indian, and Chinese ethnicity aged 40+ years, living in Singapore. Methods Diabetes was defined as nonfasting plasma glucose ≥200 mg/dl (11.1 mmol/l), glycated hemoglobin A1c (HbA1c) >6.5%, self-reported physician-diagnosed diabetes, or the use of glucose-lowering medication. Retinal photographs, were graded for the presence and severity of DR using the modified Airlie House classification system. Main Outcome Measures Diabetic retinopathy, diabetic macular edema (DME), vision-threatening diabetic retinopathy (VTDR), defined as the presence of severe nonproliferative or proliferative DR, or clinically significant macular edema (CSME). Results Of the 10 033 subjects, 2877 (28.7%) had diabetes and gradable photographs for analysis. The overall age-standardized prevalence (95% confidence interval [CI]) was 28.2% (25.9–30.6) for any DR, 7.6% (6.5–9.0) for DME, and 7.7% (6.6–9.0) for VTDR. Indians had a higher prevalence of any DR (30.7% vs. 26.2% in Chinese and 25.5% in Malays, P = 0.012); a similar trend was noted for any DME ( P = 0.001) and CSME ( P = 0.032). Independent risk factors for any DR were Indian ethnicity (odds ratio [OR], 1.41; 95% CI, 1.09–1.83, vs. Chinese), diabetes duration (OR, 1.10; 95% CI, 1.08–1.11, per year), HbA1c (OR, 1.25; 95% CI, 1.18–1.32, per %), serum glucose (OR, 1.03; 95% CI, 1.00–1.06, per mmol/l), and systolic blood pressure (OR, 1.14; 95% CI, 1.09–1.19, per 10 mmHg). Diastolic blood pressure (OR, 0.74; 95% CI, 0.65–0.84, per 10 mmHg increase), total cholesterol (OR, 0.87; 95% CI, 0.80–0.95, per mmol/l increase), and low-density lipoprotein (LDL) cholesterol (OR, 0.83; 95% CI, 0.74–0.92, per mmol/l increase) were associated with lower odds of any DR. Risk factors were largely similar across the 3 ethnic groups. Conclusions Indian Singaporeans have a higher prevalence of DR and DME compared with Chinese and Malays. Major risk factors for DR in this study were similar across the 3 ethnic groups. Addressing these risk factors may reduce the impact of DR in Asia, regardless of ethnicity.

Results from observational studies examining dyslipidemia as a risk factor for diabetic retinopathy (DR) have been inconsistent. We evaluated the causal relationship between plasma lipids and DR using a Mendelian randomization approach. We pooled genome-wide association studies summary statistics from 18 studies for two DR phenotypes: any DR (N = 2,969 case and 4,096 control subjects) and severe DR (N = 1,277 case and 3,980 control subjects). Previously identified lipid-associated single nucleotide polymorphisms served as instrumental variables. Meta-analysis to combine the Mendelian randomization estimates from different cohorts was conducted. There was no statistically significant change in odds ratios of having any DR or severe DR for any of the lipid fractions in the primary analysis that used single nucleotide polymorphisms that did not have a pleiotropic effect on another lipid fraction. Similarly, there was no significant association in the Caucasian and Chinese subgroup analyses. This study did not show evidence of a causal role of the four lipid fractions on DR. However, the study had limited power to detect odds ratios less than 1.23 per SD in genetically induced increase in plasma lipid levels, thus we cannot exclude that causal relationships with more modest effect sizes exist.

Disturbance in lipid metabolism has been suggested as a major pathogenic factor for age-related macular degeneration (AMD). Conventional lipid measures have been inconsistently associated with AMD. Other factors that can alter lipid metabolism include lipoprotein phenotype and genetic mutations. We performed a case-control study to examine the association between lipoprotein profile and neovascular AMD (nAMD) and whether the cholesterylester transfer protein (CETP) D442G mutation modulates these associations. Patients with nAMD had significantly higher concentrations of HDL and IDL compared with controls. The increase in HDL particles in nAMD patients was driven by an excess of medium-sized particles. Concurrently, patients with nAMD also had lower Apo A-1, lower VLDL and chylomicron lipoprotein. Many of these associations showed a dose-dependent association between controls, early AMD cases, and nAMD cases. Adjustment for the presence of the D442G mutation at the CETP locus did not significantly alter the increased AMD risk associated with HDL particle concentration. AMD is associated with variation in many lipoprotein subclasses, including increased HDL and IDL particles and decreased Apo A-1, VLDL, and chylomicron particles. These data suggest widespread systemic disturbance in lipid metabolism in the pathogenesis of AMD, including possible alterations in lipoprotein carrier capacity.

AimTo assess the change in vision-related quality of life (VRQoL) after treatment for neovascular age-related macular degeneration (nAMD) and factors influencing this change in an Asian population.MethodsIn this longitudinal study, 116 patients (mean age±SD=66.5±9.9 years; 59.5% male) who underwent treatment for nAMD were recruited from a tertiary eye centre in Singapore. Best-corrected visual acuity (BCVA) and the Impact of Vision Impairment (IVI) questionnaire were evaluated at baseline and month 12. We defined three categories of BCVA change in the treated eye: BCVA gain ≥2 lines; no change in BCVA; BCVA loss ≥2 lines. The main outcome measures were the Rasch-derived IVI Reading, Mobility, and Emotional Scores. Multivariable linear regression analyses assessed the influence of sociodemographic, clinical and treatment-related factors on change in VRQoL.ResultsFollowing treatment, mean treated-eye BCVA improved by almost 2 lines (−0.22±0.40 logMAR, pConclusionNearly half of patients undergoing treatment for nAMD reported a 2-line improvement in vision which was, in turn, associated with substantial positive increases in Reading Scores. Improvements in Mobility and Emotional Scores appear to be driven by factors other than visual acuity.

The aim of this work was to determine the cumulative incidence and independent risk factors of prediabetes and type 2 diabetes (T2DM) in a well-characterized cohort of Malays in Singapore.We included 1137 participants (mean age [SD]: 55 (10) years; 53.6% female) without diabetes (DM) at baseline from the Singapore Malay Eye Study, a population-based longitudinal study with baseline (2004-2006), and follow-up (2010-2013) examinations. Prediabetes was defined as an HbA1c between 5.7% and 6.4%, with no self-reported DM history or insulin/DM medication use. T2DM was defined as a random glucose level ≥200mg/dL or HbA1c6.4% or use of insulin/DM medication. Age-standardized cumulative incidence was calculated as the crude 6-year cumulative incidence standardized to Singapore's Malay population census. Multivariable modified poisson regression models were utilized to determine the risk factors of incident prediabetes and T2DM.The age-standardized 6-year cumulative incidence was 11.2% (95% CI 9.5, 13.1%) for T2DM, and 20.4% (95% CI 16.4, 25.2%) for prediabetes. Hypertension, higher body mass index (BMI) and higher Hba1c levels were associated with increased risk of T2DM, while older age and higher high density lipoprotein (HDL) cholesterol were protective (all P0.05). Only higher BMI and HbA1c levels were independently associated with incident prediabetes (all P≤0.001).While only one in ten adult Malays developed T2DM over 6-years, one in five developed prediabetes over the same time period. Our results suggest that evidence-based interventions addressing modifiable risk factors (obesity, prediabetes, hypertension, low HDL cholesterol) are needed to delay or prevent their onset.

Purpose To determine the rates and develop an initial risk prediction model for nonadherence to post screening ophthalmic referral (PSOR) in type 2 diabetes mellitus (T2DM) patients attending a national diabetic retinopathy screening program in Singapore. Methods Data from 2387 patients with T2DM (mean [standard deviation] age: 66.5 [11] years; 52.5% female patients) who underwent teleophthalmic screening between 2010 and 2014 under the Singapore Integrated Diabetic Retinopathy Program were extracted from electronic medical records. All were referred for tertiary ophthalmic management at the Singapore National Eye Centre (SNEC). Nonadherence was defined as not attending the SNEC appointment within 6 months of the assigned appointment date. Regression analysis using traditional modified Poisson and conditional inference models was used to construct and evaluate the discriminative ability of the preliminary risk prediction model to identify nonadherent individuals. Results Nonadherence rates to PSOR was 12.7% (95% confidence interval, 11.4%-14.1%). In traditional multivariable models adjusted for sociodemographic, lifestyle, and ocular factors, nonadherent individuals had higher triglyceride levels and were less likely to have a referable eye condition (P < 0.05). This model was able to identify nonadherent individuals with an accuracy (area under the curve) of 84%. In contrast, the conditional inference model was able to achieve similar discriminative ability using only participants' ocular health characteristics. Conclusions The rates of nonadherence to PSOR in Singaporean individuals with T2DM is low, with better ocular health being strongly predictive of nonadherence in our Asian population. Translational Relevance Our results may inform interventions to decrease nonadherence to PSOR.

BACKGROUND/OBJECTIVES: To compare the detailed optical coherence tomography (OCT)-based morphological parameters of pigment epithelial detachment (PED) in eyes presenting with neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV), and to assess whether these PED-associated parameters influence 1-year visual outcomes. SUBJECT/METHODS: We analysed images from a prospective observational study of treatment-naive Asian participants with nAMD or PCV. An independent reading centre graded baseline morphological features of PED on spectral-domain OCT, including greatest height, greatest width, greatest volume, morphology (predominantly dome shaped versus peaked), presence of retinal pigment epithelium (RPE) tear and cholesterol bands. The influence of these baseline features on 12 months best corrected visual acuity (BCVA) was evaluated. RESULTS: Seventy-eight eyes of 78 participants with PED were studied. In total, 40 (51.3%) participants had nAMD and 38 (48.7%) had PCV. Eyes with PCV, compared with nAMD, had PED of greater height (455.9 µm versus 389.9 µm; P = 0.035) and had higher prevalence of RPE tear (22.9 versus 5.3%; P = 0.041). In the multivariate analysis, only baseline BCVA was significantly associated with month 12 BCVA, but none of the PED-associated OCT parameters at baseline influenced month 12 BCVA. CONCLUSIONS: Despite the differences in PED height and prevalence of RPE tear between nAMD and PCV, none of these PED morphological factors on OCT at baseline significantly influenced visual outcome at 12 months.

Objective: To examine the association between vision-related quality of life (VRQoL) and depressive symptoms in residents with vision impairment (VI) in aged care facilities. Methods: In this cross-sectional study using baseline data from a cluster-randomized controlled trial (ACTRN12615000587505) assessing the effectiveness of a novel eye care model, 186 English-speaking residents (mean age 84 years, SD[standard deviation] = 8.7; 33.9% male) with VI and moderate cognitive functioning or better were recruited from 38 facilities across Victoria, Australia. VRQoL was measured using Rasch-transformed scores from the ‘Reading’; ‘Mobility’, and ‘Emotional’ scales of the Impact of Vision Impairment for Residential Care (IVI-RC) questionnaire. Outcomes were presence of depressive symptoms (binary score: Cornell Scale for Depression in Dementia [CSDD] > 0 vs. CSDD = 0) and severity of depressive symptoms (continuous CSDD score; sample range 1-21). Independent associations with presence and severity of depressive symptoms were examined using zero-inflated logistic and linear multivariable models, respectively. Results: Of the 186 participants, n = 79 (42.5%), n = 94 (50.5%) and n = 13 (7%) reported no, mild (scores 1-7), and clinically significant depressive symptoms (score ≥8), respectively. Better vision-related Mobility (OR = 0.64; 95% CI: 0.44, 0.95, p = 0.02) was associated with reduced odds of depressive symptoms. With every unit improvement in vision-related Reading (β=-0.48; 95% CI: -0.94, -0.01, p = 0.04) and Emotional (β=-0.56; 95% CI: -1.09, -0.02, p = 0.04), severity of depressive symptoms reduced, independent of sociodemographic and medical issues. Conclusion: Better VRQoL was independently associated with reduced depressive symptoms. Supporting older people in aged care to maintain optimal levels of vision-specific functioning, independence, and emotional well-being may protect their mental health.

Background/aimsTo assess the agreement in measuring retinal nerve fibre layer (RNFL) thickness between spectral-domain (SD; Cirrus HD, Carl Zeiss Meditec, USA) optical coherence tomography (OCT) and swept-source (SS; Plex Elite 9000, Carl Zeiss Meditec) OCT using an OCT angiography (OCTA) scanning protocol.Methods57 participants (12 glaucomatous, 8 ocular hypertensive and 74 normal eyes) were scanned with two OCT instruments by a single experienced operator on the same day. Circumpapillary RNFL thicknesses were automatically segmented for SD-OCT and manually segmented for SS-OCTA scans. Agreement of global RNFL thickness, as well as average thickness in four quadrants was assessed using intraclass correlation coefficients (ICCs).ResultsThere was excellent agreement in the inferior and superior quadrants and the global (all ICC >0.90), followed by good agreement in the temporal (ICC=0.79) and nasal (ICC=0.73) quadrants. The ICC values were similar in the subgroups except within the ocular hypertension group, where the nasal quadrant was less agreeable (ICC=0.31). SS-OCTA-derived RNFL thickness was on average 3 µm thicker than SD-OCT, particularly in the nasal (69.7±11.5 µm vs 66.3±9.3 µm; pConclusionsRNFL measurements taken with SS-OCTA have good-to-excellent agreement with SD-OCT, which suggests that the RNFL thickness can be sufficiently extracted from wide-field OCTA scans.

To describe the rate of development and progression of fibrosis and macular atrophy (MA) and their relationship with 1-year visual outcomes in Asian participants with neovascular age-related macular degeneration (nAMD).Review of images collected from a prospectively recruited observational cohort.Participants with treatment-naïve nAMD.All participants underwent multimodality imaging at baseline and month 12 and were treated according to standard of care. Retinal specialists evaluated color fundus photographs fluorescein and indocyanine green angiography images to determine the subtypes according polypoidal choroidal vasculopathy (PCV) and non-PCV subtypes. An independent reading center graded qualitative and quantitative morphologic features on spectral-domain OCT. Fibrosis and MA were determined based on multimodal imaging.Incidence of fibrosis and MA and their impact on visual outcome at 1 year.We included 93 eyes (48.4% PCV). Between baseline and month 12, visual acuity (VA) improved from 0.81±0.56 logarithm of the minimum angle of resolution (logMAR; Snellen equivalent, approximately 20/126) to 0.71±0.61 logMAR (Snellen equivalent, approximately 20/100; P = 0.007), and mean retinal thickness decreased from 471.1 μm to 343.4 μm (P0.001). Between baseline and month 12, prevalence of fibrosis and MA increased from 13.0% to 37.8% (P0.001) and 9.7% to 17.2% (P = 0.008), respectively. Worse baseline VA and presence of subretinal hyperreflective material (SHRM) at month 12 were associated with worse VA at month 12 after adjusting for multiple factors, whereas PCV subtype was associated with better VA at month 12. At month 12, the predominant composition of SHRM was fibrosis (82.5%).We describe significant development of fibrosis and MA in Asian nAMD eyes and show that fibrosis is the most important predictor of outcomes. These results highlight the need for therapy beyond anti-vascular endothelial growth factor inhibition to address fibrosis in Asian nAMD.

BackgroundWe examined the associations between the 6-year incidence of age-related macular degeneration (AMD) and vision-related quality of life (VRQoL), and the contribution of presenting visual acuity (VA), in an Asian population.MethodsFundus images from the Singapore Chinese Eye Study, a population-based cohort study (baseline: 2009–2011; follow-up: 2015–2017), were graded using a modified Wisconsin age-related maculopathy grading system. Incident AMD was defined as no baseline AMD in both eyes and early/late AMD in the worse eye at follow-up. Presenting VA was assessed using the logarithm of the minimum angle of resolution chart at 4 m under standard lighting conditions with habitual correction. Multiple linear regression models determined the associations between AMD incidence with changes in the Rasch-transformed scores of the Reading, Mobility and Emotional VRQoL domains of the 32-item Impact of Visual Impairment (IVI-32) questionnaire, adjusted for traditional confounders. The contribution of presenting VA to changes in VRQoL was also estimated.ResultsOf the 2251 participants without AMD at baseline (mean age (SD): 57.7 (9) years, 51.4% women), 101 (4.5%) and 11 (0.5%) developed incident early and late AMD at follow-up, respectively. Incident late AMD was associated with significant 30.3%, 32.5% and 30.9% decrements in Reading, Mobility and Emotional IVI scores, respectively. The contribution of presenting VA ranged between 1.62% and 4.35% of the observed decrements. No significant associations were noted with incident early AMD.ConclusionIncident late AMD had a substantial impact on all aspects of VRQoL, with presenting VA contributing only minimally to this longitudinal relationship.

Purpose To prospectively evaluate whether diabetic macular ischemia detected with coherence tomography angiography (OCTA) is associated with change in functional outcomes over a period of one year. Methods This is a one-year prospective, observational study that included 56 eyes with varying levels of diabetic retinopathy. All participants underwent best corrected visual acuity evaluation, swept-source OCTA and microperimetry at baseline and repeated at one year. Parafoveal vessel densities (VD) and foveal avascular zone (FAZ) areas were generated from OCTA in the superficial and deep vascular plexuses. The influence of baseline and change in OCTA parameters on change in visual acuity and retinal sensitivity over one year was evaluated. Results Over the one-year follow-up period, 16% (9) of eyes had at least one line worsening in BCVA and 7% (4) of eyes had at least 5% decrease in retinal sensitivity compared to baseline. Diabetic retinopathy progressed in 12.5%. Mean superficial vascular plexus (SVP) FAZ area increased (0.32 ± 0.15 to 0.39 ± 0.18 mm2, P = 0.003) and parafoveal VD in deep vascular plexus (DVP) decreased (49.8 ± 3.7% to 48.8 ± 2.9%, P = 0.040) at one year compared to baseline. In the multivariate regression analysis, larger baseline DVP FAZ area was associated with worsening of BCVA over one year (β = 0.16 logMAR per mm2, 95% CI 0.02 to 0.31, P = 0.032). In addition, larger decreases in SVP VD (β = -4.18 db per 10% decrease, 95% CI -6.55 to -1.80, P = 0.002) was associated with worsening of retinal sensitivity over one year. Conclusions Progression of parafoveal microvasculature changes over one year can be detected using OCTA. Larger baseline DVP FAZ area on OCTA is predictive of worsening in visual outcomes, and larger decreases in SVP VD were associated with worsening of retinal sensitivity over a course of one year in diabetic individuals.

Purpose: Evaluate efficiency, precision, and validity of RetCAT, which comprises ten diabetic retinopathy (DR) quality of life (QoL) computerized adaptive tests (CATs). Methods: In this cross-sectional clinical study, 183 English and/or Mandarin-speaking participants with DR (mean age ± standard deviation [SD] 56.4 ± 11.9 years; 38% proliferative DR [worse eye]) were recruited from retinal clinics in Singapore. Participants answered the RetCAT tests (Symptoms, Activity Limitation, Mobility, Emotional, Health Concerns, Social, Convenience, Economic, Driving, and Lighting), which were capped at seven items each, and other questionnaires, and underwent eye tests. Our primary evaluation focused on RetCAT efficiency (i.e. standard error of measurement [SEM] ± SD achieved and time needed to complete each CAT). Secondary evaluations included an assessment of RetCAT's test precision and validity Results: Mean SEM across all RetCAT tests was 0.351, ranging from 0.272 ± 0.130 for Economic to 0.484 ± 0.130 for Emotional. Four tests (Mobility, Social, Convenience, and Driving) had a high level of measurement error. The median time to take each RetCAT test was 1.79 minutes, ranging from 1.12 (IQR [interquartile range] 1.63) for Driving to 3.28 (IQR 2.52) for Activity Limitation. Test precision was highest for participants at the most impaired end of the spectrum. Most RetCAT tests displayed expected correlations with other scales (convergent/divergent validity) and were sensitive to DR and/or vision impairment severity levels (criterion validity) Conclusions: RetCAT can provide efficient, precise, and valid measurement of DR-related QoL impact. Future application of RetCAT will employ a stopping rule based on SE rather than number of items to ensure that all tests can detect meaningful differences in person abilities. Responsiveness of RetCAT to treatment interventions must also be determined Translational Relevance: RetCAT may be useful for measuring the patient-centered impact of DR severity and disease progression and evaluating the effectiveness of new therapies Refereed/Peer-reviewed

Purpose The purpose of this study was to determine the rates of, and factors associated with, eyecare utilization and spectacle affordability among Singaporeans with vision impairment (VI). Methods We included adults with VI from their second visit of the Singapore Epidemiology of Eye Disease Study. Data on eyecare utilization and spectacle affordability were collected. Low eyecare utilization was defined as no eye check ever or eye checks not even once per year in reference to at least once per year. Difficulty affording glasses was defined as glasses being rated as expensive in reference to not expensive. Results There were 985 adults (14.5%; 415 Malays, 260 Indian, and 310 Chinese; mean age [SD]: 69.5 [10.2] years; 55.4% women) with VI who answered the above questions, were included. Of these, 624 (63.4%) wore glasses. The rates of low eyecare utilization and difficulty affording eyeglasses were 31% and 63%, respectively. Compared to Chinese (23.8%) and Indians (18.8%), Malays (57.4%) had the highest rates of low eyecare utilization (P < 0.001), and most difficulty affording eyeglasses (47.2% vs. 26.1% and 26.6% in Chinese and Indians, respectively; P < 0.001). Younger age, low socioeconomic status, absence of diabetes, absence of self-reported eye conditions, and poor vision were independently associated with low eyecare utilization, whereas older age and female sex was associated with difficulty affording glasses. Conclusions In this multi-ethnic population with VI, almost one-third had low eyecare utilization and nearly two-thirds reported difficulty affording eyeglasses. Translational Relevance This will inform strategies, such as tailored eyecare utilization awareness campaigns and awareness of available subsidy schemes for at-risk Singaporeans, such as Malays.

BackgroundTo assess the clinical and patient-centred effectiveness of a novel residential ocular care (ROC) model in Australian individuals residing in residential care.MethodsIn this prospective, multicentred, randomised controlled trial conducted in 38 Australian aged-care facilities (2015–2017), 178 visually impaired individuals living in residential care facilities (mean age ±SD: 83.9±8.6 years; 65.7% women) were cluster randomised to ROC (n=95) or usual care (n=83) pathways. The ROC arm comprised a tailored and comprehensive within-site eye examination and care rehabilitation pathway, while usual care participants were given a referral to an external eyecare provider. Outcomes included presenting distance and near visual acuity (PNVA); Rasch-transformed Reading, Emotional and Mobility scores from the Impact of Vision Impairment questionnaire; quality of vision (QoV comprising Rasch-transformed Frequency, Severity and Bother domains) scores; Euroqol-5-Dimensions (raw scores); Cornell Scale for Depression (raw scores) and 6-month falls frequency, assessed at baseline and 6 months post intervention. Within-group and between-group comparisons were conducted using linear mixed models, adjusted for baseline differences in characteristics between the two arms.ResultsAt 6 months, intention-to-treat analyses showed significant between-group improvements in ROC residents compared with usual care for PNVA, Emotional and QoV scores (all pConclusionOur ROC model was effective in improving near vision, emotional well-being and perceived burden of vision-related symptoms in residential care dwellers in Australia with vision impairment. Future studies to evaluate the cost effectiveness and implementation of ROC in Australia are warranted.

This case-control study analyzes the results obtained from wide-field optical coherence tomographic angiography (OCTA) with and without removal of large vessels to assess the presence and severity of diabetic retinopathy among individuals with diabetes., Key Points Question What is the diagnostic performance of quantitative microvascular analysis using wide-field optical coherence tomographic angiography (OCTA) in eyes with diabetic retinopathy? Findings In this case-control study of 49 eyes in 27 control participants and 76 eyes in 47 participants with diabetes, microvascular metrics obtained from wide-field OCTA accurately classified severity of nonproliferative diabetic retinopathy with high sensitivity. Meaning The findings suggest that wide-field OCTA may be useful for assessment of microvascular status in eyes with diabetic retinopathy., Importance Wide-field optical coherence tomographic angiography (OCTA) may provide insights to peripheral capillary dropout in eyes with diabetic retinopathy (DR). Objective To describe the diagnostic performance of wide-field OCTA with and without large vessel removal for assessment of DR in persons with diabetes. Design, Setting, and Participants This case-control study was performed from April 26, 2018, to April 8, 2019, at a single tertiary eye center in Singapore. Case patients were those with type 2 diabetes for more than 5 years and bilateral DR diagnosed by fundus imaging; control participants included those with no self-reported history of diabetes, a fasting glucose level within the normal range in the past year, and no ocular pathologic findings. A wide-field (12 × 12-mm2) fovea-centered scan was performed using a prototype swept source OCTA system. Retinal microvasculature was examined by separating the angiograms into large vessels, capillaries, and capillary dropout regions. Main Outcomes and Measures Area under the receiver operating characteristic curve (AUC) for DR severity discrimination using wide-field vascular metrics. Retinal perfusion density (RPD), capillary perfusion density (CPD), large vessel density (LVD), and capillary dropout density (CDD) were calculated. Low-contrast regions were excluded from the calculation. Results A total of 49 eyes in 27 control participants (17 male [63.0%]; mean [SD] age, 59.96 [7.63] years; age range, 44-79 years) and 76 eyes in 47 patients with diabetes (29 male [61.7%]; mean [SD] age, 64.36 [8.08] years; range, 41-79 years) were included. Among eyes in patients with diabetes, 23 were in those with diabetes but no DR, 25 in those with mild nonproliferative DR, and 28 in those with moderate to severe nonproliferative DR. There was no difference in RPD, CPD, LVD, and CDD between the control group and the group with diabetes and no DR. There was a stepwise decrease in RPD, CPD, and CDD in the diabetes with no DR, mild nonproliferative DR, and moderate to severe nonproliferative DR groups, whereas LVD was not associated with DR staging. The nonproliferative DR group had decreased RPD, CPD, and CDD compared with the control group. The CPD had higher AUCs than RPD for discriminating diabetes with nonproliferative DR (combined mild and moderate to severe nonproliferative DR) vs no DM (AUC, 0.92 [95% CI, 0.87-0.98] vs 0.89 [95% CI, 0.83-0.95], P = .01), diabetes with no DR vs mild nonproliferative DR (AUC, 0.81 [95% CI, 0.68-0.94] vs 0.77 [95% CI, 0.64-0.91], P = .18), and mild nonproliferative DR vs moderate to severe nonproliferative DR (AUC, 0.82 [95% CI, 0.71-0.94] vs 0.78 [95% CI, 0.65-0.91], P = .01) but similar AUCs for no DM vs diabetes with no DR. The total perfusion density and CPD in wide-field OCTA had better discriminative power than the central 6 × 6-mm2 field (CPD, 0.89 [95% CI, 0.83-0.95] vs 0.84 [95% CI, 0.77-0.92], P = .06; total perfusion density, 0.93 [95% CI, 0.87-0.98] vs 0.90 [95% CI, 0.83-0.96], P = .06). Conclusions and Relevance The findings suggest that wide-field OCTA provides information on microvascular perfusion and may be useful for detecting predominant peripheral capillary dropout in eyes with nonproliferative DR. A vascular selectivity approach excluding the large vessels may improve the discriminative power for different stages of DR.

Population-based data investigating generational differences in the risk of incident cardiovascular disease (CVD) and its risk determinants are rare. We examined the 6-year incidence of CVD and its risk factors in first- and second-generation ethnic Indians living in Singapore. 1749 participants (mean age [SD]: 55.5 [8.8] years; 47.5% male) from a population-based, longitudinal study of Indian adults were included for incident CVD outcome. Incident CVD was defined as self-reported myocardial infarction, angina pectoris or stroke which developed between baseline and follow-up. CVD-related risk factors included incident diabetes, hypertension, hyperlipidemia, obesity and chronic kidney disease (CKD). For incident CVD outcome, of the 1749 participants, 406 (23.2%) and 1343 (76.8%) were first and second-generation Indians, respectively. Of these, 73 (4.1%) reported incident CVD. In multivariable models, second-generation individuals had increased risk of developing CVD (RR = 2.04; 95% CI 1.04, 3.99; p = 0.038), hyperlipidemia (RR = 1.27; 95% CI 1.06, 1.53; p = 0.011), and CKD (RR = 1.92; 95% CI 1.22, 3.04; p = 0.005), compared to first-generation Indians. Second-generation Indians have increased risk of developing CVD and its associated risk factors such as hyperlipidemia and CKD compared to first-generation immigrants, independent of traditional CVD risk factors. More stratified and tailored CVD prevention strategies on second and subsequent generations of Indian immigrants in Singapore are warranted.

AimsDiabetes is a major public health problem in migrants and ethnic minorities worldwide. We determined the incidence and risk factors of diabetic retinopathy (DR) in migrant Indians living in Singapore.MethodsWe included data from 759 Indian adults with diabetes, who participated in the baseline (aged 40–80 years, 2007–2009) and 6-year follow-up 2012–2015 of the Singapore Indian Eye Study. Retinal photographs were graded for the presence and severity of DR using modified Airlie House Classification. Incidence was assessed in participants who were free of DR at baseline visit (n=501), while progression in those with DR but free of proliferative DR at baseline visit (n=189). Risk factors included demographic, lifestyle, socioeconomic, family history, genes, duration of diabetes, glycaemic control, insulin use, ocular and clinical factors.ResultsThe 6-year age-standardised DR incidence and progression were 21.89% and 33.45%, respectively. HbA1c (risk ratio (RR) 1.41, 95% CI 1.28 to 1.55 per unit increase), current smoking (RR 1.63, 95% CI 1.02 to 2.62) and insulin use (RR 2.63, 95% CI 1.44 to 4.82) were associated with higher incidence, whereas estimated cerebrospinal fluid pressure (RR 0.90, 95% CI 0.82 to 0.98) and body mass index (BMI) (RR 0.74, 95% CI 0.60 to 0.93) were associated with lower incidence of DR. Higher HbA1c (RR 1.26, 95% CI 1.13 to 1.42), BMI (RR 1.26, 95% CI 1.02 to 1.56) and estimated cerebrospinal fluid pressure (RR 1.11, 95% CI 1.02 to 1.21) were associated with DR progression. The population attributable risk of HbA1c >8% was 41.29% and 49.63% for DR incidence and progression.ConclusionDR incidence and progression in migrant Indians living in Singapore was more than double that reported in Indians living in urban India. Consistent with past studies, poor glycaemic control was an important predictor for incidence and progression of DR.