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Introduction: We investigated the knowledge, attitudes and practice (KAP) towards coronavirus disease 2019 (COVID-19) and its 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 symptoms and six government-endorsed preventive measures related to COVID-19 were evaluated. Multivariable regression models were used to identify sociodemographic and health-related factors associated with KAP in our sample. Associations between knowledge/attitude scores and practice categories were determined using logistic regression. Seventy-eight participants were interviewed qualitatively about the practice of additional preventive measures and data were analysed thematically., Results: Mean awareness score of COVID-19 symptoms was 7.2/10. The most known symptom was fever (93.0%) and the least known was diarrhoea (33.5%). Most participants knew all six preventive measures (90.4%), perceived them as effective (78.7%) and practised 'wear a mask' (97.2%). Indians, Malays and participants living in smaller housing had poorer mean scores for knowledge of COVID-19 symptoms. Older participants had poorer attitudes towards preventive measures. Compared to Chinese, Indians had lower odds of practising three out of six recommendations. A one-point increase in score for knowledge and attitudes regarding preventive measures resulted in higher odds of always practising three of six and two of six measures, respectively. Qualitative interviews revealed use of other preventive measures, for example, maintaining a healthy lifestyle., Conclusions: Elderly Singaporeans displayed high levels of KAP about COVID-19 and its related preventive measures, with a positive association between levels of knowledge/attitude and practice. However, important ethnic and socioeconomic disparities were evident, indicating that key vulnerabilities remain, which require immediate attention., Competing Interests: None

Purpose: To use optical coherence tomography angiography (OCTA) parameters from both the retinal and choroidal microvasculature to detect the presence and severity of diabetic retinopathy (DR)., Method: This is a cross-sectional case-control study. OCTA parameters from retinal vasculature, fovea avascular zone (FAZ) and choriocapillaris were evaluated from 3×3 mm 2 fovea-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))., Results: 35 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 (p<0.01), except for the deep plexus FAZ area (p=0.619). Choriocapillaris parameters allowed to better discriminate between no DM versus DM no DR group compared with retinal parameters (areas under the ROC curve=0.954 vs 0.821, p=0.006). A classification model including retinal and choroidal microvasculature significantly improved the discrimination between DR and no DR compared with each parameter separately (p=0.029)., Conclusions: Evaluating OCTA parameters from both the retinal and choroidal microvasculature in 3×3 mm scans improves the discrimination of DM and early DR., Competing Interests: Competing interests: GT reported receiving travel support from Carl Zeiss Pte Ltd; receiving personal fees and consultancy fees from Novartis; receiving grants from Bayer AG and Santen Pharmaceutical Company, Ltd; and receiving travel support from Alcon outside the submitted work., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Aims: To examine the relationship between vision impairment (VI) and employment outcomes in a multiethnic Asian population., Methods: We 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 <0.6 logMAR) and moderate to severe (VA ≥0.6 logMAR). Self-reported employment statuses at both baseline and follow-up were used as outcomes. Underemployment was defined as a decline in occupational skill level, categorised by International Standard Classification of Occupations, at follow-up compared with baseline. Multinomial logistic regression models were used to determine independent associations between VI and various employment outcomes, adjusted for variables that were found to significantly differ across employment statuses., Results: Presenting 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, p<0.001, respectively). At follow-up, participants with any VI at baseline were more likely to be underemployed (OR 1.46, 95% CI 1.03 to 2.05, p=0.033)., Conclusion: VI, 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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To compare quality of life (QoL) between patients who receive bilateral small-incision lenticule extraction (SMILE) or laser in situ keratomileusis (LASIK) vs bilateral sequential SMILE-LASIK (BSSL) surgery., Setting: Singapore National Eye Centre, Singapore., Design: Retrospective cohort study., Methods: 2 patient cohorts were recruited (2010-2012; 2014-2016). The bilateral SMILE (BS) and bilateral LASIK (BL) groups comprised patients (mean ± SD age: 30.3 ± 6.5, 50% male) from a prospective nonrandomized study who chose SMILE and LASIK, respectively. The BSSL group comprised patients (mean ± SD age: 28.6 ± 6.2, 64.3% male) randomized to receive SMILE in 1 eye and LASIK in the other. Rasch-scaled scores of the QoL Impact of Refractive Correction questionnaire between groups postoperatively at 1 and 3 months were compared., Results: At month 1, scores on 3 QoL without emotional well-being items were worse in the BSSL (n = 70) compared with the BL group (n = 25), specficially, "using sunglasses" (β: -20.6, 95% CI, -34.3 to -6.9), "reliance on refractive correction" (-23.1, 95% CI, -40.9 to -5.4), and "medical complications from optical correction" (β: -14.8, 95% CI, -27.9 to -1.7). Emotional well-being (overall), and items "feeling able to do things" (β: 11.0, 95% CI, 1.6-20.4) and "feeling eager to try new things" (β: 14.1, 95% CI, 3.6-24.6) were better in the BSSL compared with the BS group (n = 25). No substantive differences were observed at month 3., Conclusions: Refractive correction-related QoL differences at month 1 between BSSL and BS/BL patients attenuated by month 3. Bilateral sequential SMILE-LASIK surgery appeared unlikely to negatively affect QoL beyond 3 months., (Copyright © 2023 Published by Wolters Kluwer on behalf of ASCRS and ESCRS.)

Purpose: To identify genetic alleles associated with differences in choroidal thickness (CT) in a population-based multiethnic Asian cohort., Methods: A population-based multiethnic Asian cohort without retinal pathology was subjected to spectral-domain OCT (SD-OCT) and genotyping of risk alleles in CFH, VIPR2, ARMS2, and CETP. Subfoveal choroidal thickness (SFCT) values were assessed from SD-OCT, and associations with the risk alleles were determined for each cohort., Results: A total of 1045 healthy Asian individuals (550 Chinese, 147 Indians, 348 Malays) were prospectively enrolled in the study. Several CFH alleles (rs800292, rs1061170, and rs1329428) were associated with increased SFCT in Indians (+18.7 to +31.7 µm; P = 0.001-0.038) and marginally associated with decreased SFCT in Malays (-12.7 to -20.6 µm; P = 0.014-0.022). Haplotype analysis of CFH revealed variable associations with SFCT among races, with the H6 haplotype being associated with a 29.08-µm reduction in SFCT in the Chinese cohort (P = 0.02) but a 35.2-µm increase in SFCT in the Indian cohort (P < 0.001). Finally, subfield analysis of the Chinese cohort identified associations between the CFH risk allele rs1061170 and reduced CT in the nasal and superior sectors (-20.2 to -25.8 µm; P = 0.003-0.027)., Conclusions: CFH variants are variably associated with CT among Asian ethnic groups. This has broad implications for the pathogenesis of common diseases such as age-related macular degeneration and central serous choroidopathy, the pathogenesis of which is associated with CT.

Background/aims: To 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)., Methods: A 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., Results: Over the 1-year follow-up, VA improved (0.025 logMAR/ month, 95% CI 0.015 to 0.035) and FAZ area decreased (-0.020 mm 2 /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., Conclusions: OCTA measures of vascular perfusion in the macula may provide new pathophysiological insights and prognostic information related to macula-off RRD., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: We 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., Methods: Fundus 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., Results: Of 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., Conclusion: Incident late AMD had a substantial impact on all aspects of VRQoL, with presenting VA contributing only minimally to this longitudinal relationship., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

To determine the differential impact of the irreversible eye diseases on vision-related quality of life (VRQoL) in a multi-ethnic Asian population. 2652 participants from the Singapore Epidemiology of Eye Disease Study, with any of the following early and late-stage eye conditions including age-related macular degeneration (AMD, n = 158), diabetic retinopathy (DR, n = 105; non vision threatening [non-VTDR]; VTDR), glaucoma (n = 57) and myopic macular degeneration (MMD, n = 106), or none of the above (controls, 2226 [83.9%]) were included. Rasch-scaled scores of the Emotional well-being Mobility and Reading subscales of the Impact of Vision Impairment (IVI) questionnaire, collectively referred to as "VRQoL" were assessed. Multivariable linear regression analyses and pairwise comparisons adjusting for age, gender, ethnicity, socio-economic status, BMI, smoking, alcohol use, presence of systemic diseases and presenting VI were performed to assess and compare the impact of the presence and severity of each eye condition on the three IVI domains. Multivariable adjusted pairwise comparisons of VRQoL between early stages of the four eye diseases showed no significant differences (all P > 0.05). For late stage diseases, individuals with VTDR had significantly larger decrements in Emotional well-being compared to glaucoma (β - 0.81; 95% CI - 1.47 to - 0.16) and MMD (β - 1.17; 95% CI - 2.16 to - 0.18); and Reading decrements compared to glaucoma (β - 0.66; 95% CI - 1.22 to - 0.11). When compared to late glaucoma, individuals with late AMD (β - 0.76; 95% CI - 1.50 to - 0.01) had significantly larger IVI Mobility subscale decrements. VTDR and late AMD, appear to have the greatest impact on VRQoL, compared to late glaucoma and MMD, suggesting a differential impact of late-stage eye disease categorization on VRQoL., (© 2022. The Author(s).)

Sensory impairments and sarcopenia are both highly prevalent age-related conditions, with the former having been postulated to contribute to the pathogenesis of the latter condition. Confirming this hypothesis may therefore help to better inform strategies for early treatment and intervention of sarcopenia. We performed a systematic review of the current literature examining the relationships between four major sensory impairments [vision (VI), hearing (HI), smell (SI), and taste (TI)] with (i) sarcopenia; and (ii) its associated components (low handgrip strength, slow gait speed, and low muscle mass). PubMed, EMBASE, CINAHL, and Cochrane Library databases were searched for observational studies investigating the relationship of VI, HI, SI, and TI with sarcopenia, low handgrip strength, slow gait speed, and low muscle mass, in adults aged 50 years or older, from inception until 24 May 2021. The risk of bias of the included studies was assessed using the Newcastle-Ottawa Scale. This study was registered with PROSPERO, reference CRD42021247967. Ten cross-sectional and three longitudinal population-based studies of community-dwelling adults (N = 68 235) were included, with five studies investigating more than one sensory impairment. In total, 8, 6, 3, and 1 studies investigated the relationship between VI, HI, SI, and TI and sarcopenia and its related components, respectively. Follow-up duration for the longitudinal studies ranged from 4 to 11 years. All studies had a low or moderate risk of bias. We found that the presence of VI and SI, but not TI, independently increased the odds of sarcopenia. In addition, VI and SI were each independently associated with low muscle mass; and VI, HI, and SI were each independently associated with slow gait speed. However, we found inconclusive evidence for the associations between VI, HI and SI, and low handgrip strength. Our systematic review suggests a potential association between the presence of single or multiple sensory impairments and a greater likelihood of sarcopenia and/or deficits in its associated components, especially for VI, HI, and SI. Prospective studies are needed to untangle the relationship between sensory impairment and sarcopenia to better inform clinical guidelines for disease prevention and management., (© 2022 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.)

Purpose: 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., Methods: 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., Results: 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 P < 0.05). 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., Conclusion: 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 < .001), representing reductions of 20.7% to 76.1% in quality-adjusted life-years compared with a health state that included preperimetric glaucoma. Mean (SD) Glau-U utilities also decreased as better-eye vision impairment worsened from 0.67 (0.23) for none to 0.58 (0.32) for mild to 0.46 (0.29) for moderate to severe vision impairment. Glau-U utilities demonstrated moderate correlations with better-eye (r = 0.34; P < .001) and worse-eye (r = 0.33; P < .001) mean deviation scores and low correlations with EuroQol 5-Dimension utilities (r = 0.22; P < .001), supporting convergent and divergent validity., Conclusions and Relevance: Use of Glau-U revealed large decrements in utility that were associated with late-stage glaucoma, suggesting that this new instrument may be useful for cost-effectiveness analyses of interventions and informing resource allocation policies for glaucoma and vision loss.

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., (Copyright © 2020 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

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., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

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., (Copyright © 2020 American Academy of Ophthalmology. All rights reserved.)

Background: To investigate the longitudinal associations between person-level and area-level socioeconomic status (PLSES and ALSES, respectively) with diabetic retinopathy (DR) and visual impairment (VI) in Asians with diabetes mellitus (DM)., Methods: In this population-based cohort study, we included 468 (39.4%) Malays and 721 (60.6%) Indians with DM, with a mean age (SD) of 58.9 (9.1) years; 50.6% were female and the mean follow-up duration was 6.2 (0.9) years. Individual PLSES parameters (education, monthly income and housing type) were quantified using questionnaires. ALSES was assessed using the Socioeconomic Disadvantage Index derived from Singapore's 2010 areal census (higher scores indicate greater disadvantage). Incident DR and VI were defined as absent at baseline but present at follow-up, while DR and VI progression were defined as a ≥1 step increase in severity category at follow-up. Modified Poisson regression analysis was used to determine the associations of PLSES and ALSES with incidence and progression of DR and VI, adjusting for relevant confounders., Results: In multivariable models, per SD increase in ALSES score was associated with greater DR incidence (risk ratio (95% CI) 1.27 (1.13 to 1.44)), DR progression (1.10 (1.00 to 1.20)) and VI incidence (1.10 (1.04 to 1.16)), while lower PLSES variables were associated with increased DR (low income: 1.68 (1.21 to 2.34)) and VI (low income: 1.44 (1.13 to 1.83); ≤4 room housing: 2.00 (1.57 to 2.54)) incidence., Conclusions: We found that both PLSES and ALSES variables were independently associated with DR incidence, progression and associated vision loss in Asians. Novel intervention strategies targeted at low socioeconomic status communities to decrease rates of DR and VI are warranted., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

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.

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.

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., (© The Author(s) 2020. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: To assess the clinical and patient-centred effectiveness of a novel residential ocular care (ROC) model in Australian individuals residing in residential care., Methods: In 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., Results: At 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 p<0.05) These significant findings were retained in per-protocol analyses. No other between-group changes were observed., Conclusion: Our 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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To examine the relationship between macular microvasculature parameters and functional changes in persons with diabetic retinopathy (DR)., Methods: 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., Results: 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)., Conclusion: 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.

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 < 0.001)., 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., Competing Interests: Disclosure: E.K. Fenwick, None; R.E.K. Man, None; A.T.L. Gan, None; A. Aravindhan, None; C.S. Tey, None; H.J.T. Soon, None; D.S.W. Ting, None; S.I.Y. Yeo, None; S.Y. Lee, None; G. Tan, None; T.Y. Wong, None; E.L. Lamoureux, None, (Copyright 2020 The Authors.)

Background/aims: To 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., Methods: 57 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)., Results: There 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; p<0.001) and temporal (75.6±13.7 µm vs 67.9±12.3 µm; p<0.001) quadrants., Conclusions: RNFL 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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background/aims: To 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., Methods: In 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., Results: Of 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., Conclusion: Overall, 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 Registration: ACTRN12611000720910., Competing Interests: Competing interests: IG has the following conflicts of interest to declare: Advisory Board member for Allergan, Novartis, Mundipharma; Speaker Bureau for Allergan, Novartis; Travel support from Pfizer. KM has the following conflicts of interest to declare: Consultant to Allergan, Novartis, Quethera, Sensimed., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

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., Competing Interests: Disclosure: J.T. Sia, None; A.T.L. Gan, None; B.P. Soh, None; E. Fenwick, None; J. Quah, None; T. Sahil, None; Y. Tao, None; N.C. Tan, None; C. Sabanayagam, None; E.L. Lamoureux, None; R.E.K. Man, None, (Copyright 2020 The Authors.)

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., Competing Interests: Disclosure: P. Gupta, None; S. Majithia, None; E.K. Fenwick, None; A.T.L. Gan, None; Y.-C. Tham, None; S. Poh, None; S. Thakur, None; C. Sabanayagam, None; T.Y. Wong, None; C.-Y. Cheng, None; E.L. Lamoureux, None, (Copyright 2020 The Authors.)

Background/aims: To 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., Methods: The 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., Results: Of 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)., Discussion: The 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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

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: 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., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Aims: Diabetes 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., Methods: We 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., Results: The 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., Conclusion: DR 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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background/aim: The relationship between diabetic retinopathy (DR) and cognitive impairment (CI) is unclear due to equivocal findings from cross-sectional studies and a lack of long-term data. In this population-based cohort study, we investigated the longitudinal association between the severity of DR and the incidence of CI., Methods: 682 participants with diabetes, gradable retinal photographs and no CI at baseline 2004-2011) and complete relevant data at follow-up 2010-2016 from the Singapore Epidemiology of Eye Disease Study were included. CI was assessed using the validated Abbreviated Mental Test (AMT), defined as scores of ≤6 and ≤8 for those with 0-6 and >6 years of formal education, respectively. Six-year incident CI was defined as having no CI at baseline but present at the follow-up visit., Results: Of the 682 included participants, 483 (70.8%) had no DR and 199 (29.2%) had any DR. Of those with DR, 142 (20.8%) had minimal/mild DR and 57 (8.4%) had moderate or worse DR at baseline. At the follow-up visit, 40 (5.9%) participants had incident CI based on AMT. In multivariate analysis compared with participants without DR, those with any DR had more than twofold increased odds of incident CI (OR (95% CI): 2.32 (1.07 to 5.03)). Participants with moderate or worse DR had threefold increased odds of developing CI (3.41 (1.06 to 11.00)), compared with those with no DR., Conclusions: DR, particularly at the more severe stages, is associated with increased risk of developing CI, independent of vision and other risk factors., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

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.

Background/aims: To assess the independent impact of diabetic retinopathy (DR) on three domains of vision-related quality of life (VRQoL) in a Chinese Singapore population., Methods: The 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., Results: Of 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., Conclusions: We 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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) [year]. No commercial re-use. See rights and permissions. Published by BMJ.)

This study examined the associations of body mass index (BMI), waist circumference (WC), waist-hip ratio (WHR) and waist-height ratio (WHtR) with diabetic kidney disease (DKD) in a clinical sample of Asian patients with type 2 diabetes (T2DM); substantiated with a meta-analysis of the above associations. We recruited 405 patients with T2DM (mean (standard deviation (SD)) age: 58 (7.5) years; 277 (68.4%) male; 203 (50.1%) with DKD) from a tertiary care centre in Singapore. DKD was defined as urinary albumin-creatinine ratio >3.3 mg/mmoL and/or estimated glomerular filtration rate <60 mL/min/1.73 m². All exposures were analysed continuously and categorically (World Health Organization cut-points for BMI and WC; median for WHR and WHtR) with DKD using stepwise logistic regression models adjusted for traditional risk factors. Additionally, we synthesized the pooled odds ratio of 18 studies ( N = 19,755) in a meta-analysis of the above relationships in T2DM. We found that overweight and obese persons (categorized using BMI) were more likely to have DKD compared to under/normal weight individuals, while no associations were found for abdominal obesity exposures. In meta-analyses however, all obesity parameters were associated with increased odds of DKD. The discordance in our abdominal obesity findings compared to the pooled analyses warrants further validation via longitudinal cohorts.

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.

Background: Women with gestational diabetes mellitus (GDM) are at greater risk of metabolic syndrome (MetS). We studied the association between second-trimester retinal microvasculature and 5-year MetS incidence in women with GDM., Methods: A total of 142 mothers with GDM were recruited and followed up 5years after delivery. Retinal photography was performed at 26-28weeks gestation and metabolic outcomes were assessed at the 5-year postpartum follow-up visit. GDM and MetS were defined based on World Health Organization (WHO) guidelines and Adults Treatment Panel (ATP) III guidelines, respectively. Modified-Poisson regression was applied to study the association between second-trimester retinal microvasculature and incident 5-year maternal MetS, after adjusting for major confounders. Area under the curve (AUC) was calculated based on the final model., Results: Our prospective cohort reported a 9.2% incidence rate of 5-year MetS among women with GDM. After adjusting for maternal age, ethnicity, college degree, pre-pregnancy BMI and fasting glucose at 26-28week gestation, each 10μm widening in retinal venular caliber was associated with an increased relative risk of 1.6 (95% confidence interval [CI]: 1.0, 2.8) in incident MetS. In addition to traditional risks of pre-pregnancy BMI and fasting glucose level at 26-28week gestation, retinal venular caliber mildly increased the prediction of 5-year maternal MetS by 1.8%., Conclusions: Second-trimester retinal venular widening was associated with incident 5-year maternal MetS in women with GDM. Our study suggests that mother with GDM at risk of future MetS development may have already presented retinal microvascular abnormalities during pregnancy., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Importance: A patient’s perceived barriers to diabetes self-management (DSM) may affect his or her risk of diabetic retinopathy (DR); however, few studies have examined this association., Objective: To examine the association between perceived barriers to DSM and the severity spectrum of DR in Asian patients with type 2 diabetes., Design, Setting, and Participants: A cross-sectional clinic-based study, the Singapore Diabetes Management Project, was conducted from December 28, 2010, to March 20, 2013, at the Singapore National Eye Centre, a tertiary eye care institute. After excluding patients with type 1 diabetes and ungradable fundus images, 361 participants were included in the analyses. Statistical analysis was conducted from July 20 to September 8, 2017., Exposure: The degree of perceived barriers to DSM was assessed using a 23-item questionnaire comprising items about knowledge of DSM, access to care, and confidence in health care professionals. Rasch analysis was used to optimize the scale’s psychometric properties, with lower scores indicating a higher degree of self-perceived barriers., Main Outcomes and Measures: Diabetic retinopathy was graded from 2-field retinal images into categories of no DR (Early Treatment Diabetic Retinopathy Study levels 10-15; n = 154), mild to moderate DR (levels 20-43; n = 112), and severe DR (levels ≥53 and/or presence of clinically significant macular edema; n = 95) using the modified Airlie House classification system of DR. Multinomial logistic regression models were used to assess the association between perceived barriers and severity of DR in the worse-affected eye., Results: Among the 361 participants (105 women and 256 men; mean [SD] age, 57 [8] years), a greater magnitude of perceived barriers to DSM was independently associated with higher odds of having any DR (odds ratio, 1.32; 95% CI, 1.06-1.66), mild to moderate DR (odds ratio, 1.30; 95% CI, 1.01-1.68), and severe DR (odds ratio, 1.36; 95% CI, 1.03-1.79). This association was independent of diabetes control (hemoglobin A1c, blood pressure, and lipid levels), presenting visual acuity, and socioeconomic indicators., Conclusions and Relevance: These results suggest that greater perceived barriers to DSM are independently associated with severity of DR. Although longitudinal data are needed, these findings suggest that evidence-based interventions to reduce patient-, practitioner-, and system-related barriers to diabetes care may help reduce the risk of DR.

Retinal angiomatous proliferation (RAP) is a unique variant of neovascular age-related macular degeneration. Published studies have estimated that up to 15% of patients with neovascular age-related macular degeneration have RAP. Clinical features frequently associated with RAP include bilateral disease, presence of pigment epithelial detachments, and reticular pseudodrusen. RAP is more frequently associated with the development of retinal pigment epithelial tears and geographic atrophy that can lead to severe vision loss. Recent advances in retinal and choroidal imaging technology have furthered our understanding of RAP. Although indocyanine green angiography remains the gold standard diagnostic tool, optical coherence tomography has improved the precision by which neovascular age-related macular degeneration with RAP lesions can be diagnosed, staged, and monitored. Anti-vascular endothelial growth factor therapy is currently the first line of treatment. Other treatment options including combination of photodynamic therapy with antiangiogenic agent intravitreal injections or corticosteroids may also achieve a reasonable therapeutic outcome; however, RAP may portend a more guarded visual prognosis than typical choroidal neovascularization because of variable treatment response and dependence on the disease stage. Future basic and clinical research is needed to clarify the pathophysiology, definition and classification, optimal treatment regimen, and long-term outcome of RAP., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Aims: 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., Methods: 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 HbA1c>6.4% 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., Results: 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 P<0.05). Only higher BMI and HbA1c levels were independently associated with incident prediabetes (all P≤0.001)., Conclusions: 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., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Importance: Understanding the link between ethnicity and health is critical to making appropriate public policy decisions. Few population-level data are available about this connection, however, including the influence of ethnicity on the association between age-related macular degeneration (AMD) and vision-specific functioning (VSF)., Objective: To identify the influence of ethnicity on VSF among Chinese, Malay, and Indian patients with AMD., Design, Setting, and Participants: This cross-sectional, population-based study relied on patients and their data from 3 population-based studies in 3 ethnic groups: Chinese, Malay and Indian. Of 10 033 Chinese, Malay, and Indian adults who participated in the study, 9962 (99.3%) who had gradable fundus images and Visual Function Index (VF-11) data available were included in the analyses for the present study. Uniocular presenting distance visual acuity was measured using the logMAR chart. Separate multiple linear regression models examined the association between AMD and VSF in the 3 ethnic groups, adjusting for age, sex, presenting visual acuity in the better-seeing eye, educational level, income, smoking status, hypertension, diabetes, cardiovascular disease, total cholesterol level, and other eye conditions. Data were collected between January 20, 2004, and December 19, 2011; data analysis was conducted between November 12, 2015, and December 28, 2016., Exposures: Age-related macular degeneration according to fundus photographs graded using a modified Wisconsin Age-Related Maculopathy Grading System., Main Outcomes and Measures: Rasch analysis was used to convert VF-11 questionnaire scores to estimated interval measures of VSF., Results: Of the 9962 participants, the mean (SD) age was 58.8 (10.4) years; 4909 (49.3%) were male; 590 (5.9%) had early AMD (241 Chinese, 161 Malays, and 188 Indians) and 60 (0.6%) had late AMD (25 Chinese, 21 Malays, and 14 Indians). In the adjusted models, compared with no AMD, early AMD was associated with a small reduction in VSF (2.9%; β = -0.12; 95% CI, -0.23 to -0.00; P = .046) in the Chinese group but not in the Indian and Malay groups. Moreover, Chinese participants with late AMD had a clinically significant 19.1% loss of VSF (β = -0.78; 95% CI, -1.13 to -0.43, P < .001). In the Malay group, those with late AMD had a 13.5% drop in VSF (β = -0.49; 95% CI, -1.01 to 0.04; P = .07) compared with their counterparts without AMD. Similarly, late AMD was not associated with VSF in the Indian group., Conclusions and Relevance: Early and late AMD negatively affected VSF in Chinese but not in Indian and Malay participants. This finding suggests that there is an independent ethnic influence in the association of the disease with VSF in multiethnic Asian populations, thus warranting ethnicity-based strategies to delay the onset or progression of AMD.