Synergistic Impact of Visual and Cognitive Impairments on Health-Related Quality of Life in a Multiethnic Asian Population.

INTRODUCTION: The concomitant impact of visual impairment (VI) and cognitive impairment (CI) on health-related quality of life (HRQoL) in older adults is unclear. We aimed to determine the synergistic effect of baseline VI and CI on HRQoL decline at 6 years in multiethnic Asians. METHODS: We included Chinese, Malay, and Indian adults aged ≥60 years who participated in baseline (2004-2011) and 6-year (2011-2017) follow-up visits of the Singapore Epidemiology of Eye Diseases Study, a population-based cohort study in Singapore. Visual acuity (VA) was objectively measured at both visits, with VI defined as presenting VA >0.3 LogMAR in the better eye. CI was defined as Abbreviated Mental Test scores of ≤6 and ≤8 for individuals with ≤6 and >6 years of formal education, respectively. HRQoL was measured using the European Quality of Life-5 Dimensions (EQ-5D) questionnaire. HRQoL decline was defined as the difference in the composite EQ-5D scores at baseline and 6-year follow-up and deemed clinically meaningful if the reduction was equal to or larger than the minimal clinically important difference. Multivariable linear regression assessed the independent associations and synergism (ß interaction) between baseline VI and CI on EQ-5D decline. RESULTS: Of the 2,433 participants (mean [SD] age: 67.6 [5.5]) at baseline, 559, 120, and 151 had VI only, CI only, and both impairments, respectively. HRQoL decline in individuals with baseline comorbid VI-CI was clinically meaningful and was 2.0 times (ß = -0.044, 95% confidence interval: -0.077 to -0.010) and 3.7 times (ß = -0.065, 95% confidence interval: -0.11 to -0.022) larger than those with VI only and CI only, respectively. Importantly, there was a significant synergism (ß interaction = -0.048, 95% confidence interval: -0.095 to -0.001) between baseline VI and CI as predictors of HRQoL decline, suggesting that individuals having both conditions concurrently had a greater HRQoL reduction than the sum in those with VI alone and CI alone. The affected HRQoL domains included mobility and usual activities. CONCLUSIONS: Concomitant VI-CI potentiated HRQoL decline to a greater extent than the sum of individual contributions of VI and CI, suggesting synergism. Our results suggest that rehabilitative interventions such as the use of mobility aids and occupational therapy are needed to maintain HRQoL in older adults with concomitant VI-CI. Moreover, preventive interventions targeting at early detection and management of both VI and CI may also be beneficial.

OPTICAL COHERENCE TOMOGRAPHY FEATURES OF POLYPOIDAL LESION CLOSURE IN POLYPOIDAL CHOROIDAL VASCULOPATHY TREATED WITH AFLIBERCEPT.

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.

The Differential Impact of Age on Vision-Related Quality of Life across the Visual Impairment Spectrum.

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.

The Bidirectional Relationship between Vision and Cognition: A Systematic Review and Meta-analysis.

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.

Vision, vision-specific functioning and mobility, and their relationship with clinically assessed cognitive impairment.

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.

POLYPOIDAL CHOROIDAL VASCULOPATHY FEATURES VARY ACCORDING TO SUBFOVEAL CHOROIDAL THICKNESS.

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.

Using Uniocular Visual Acuity Substantially Underestimates the Impact of Visual Impairment on Quality of Life Compared with Binocular Visual Acuity.

PURPOSE: 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. DESIGN: The Singapore Chinese Eye Study 2 (2015-2017), a population-based, cross-sectional study. PARTICIPANTS: One thousand eight hundred twenty-two individuals (mean age, 66.2 years [standard deviation, 8.9 years]; 51.1% women) were included. METHODS: 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 ß estimates between the associations were statistically significant. MAIN OUTCOME MEASURES: 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. RESULTS: Although every 2-line increase (worsening) in binocular VA and uniocular VA was associated independently with decrements in emotional, mobility, and reading IVI scores (P < 0.05 for all), the reductions in all VRQoL domains were substantially lower (P < 0.1) when using either the better-eye VA (compared with binocular VA ß-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 ß estimates, -38.9%, -58.1%, and -57.5% reduction in emotional, mobility, and reading IVI scores, respectively) to quantify vision loss. CONCLUSIONS: 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.

DIABETIC MACULAR ISCHEMIA: Correlation of Retinal Vasculature Changes by Optical Coherence Tomography Angiography and Functional Deficit.

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.

High vision-related quality of life indices reduce the odds of depressive symptoms in aged care facilities.

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 (ß=-0.48; 95% CI: -0.94, -0.01, p = 0.04) and Emotional (ß=-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.

Prevalence, determinants and association of unawareness of diabetes, hypertension and hypercholesterolemia with poor disease control in a multi-ethnic Asian population without cardiovascular disease.

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.

Ethnic Differences in the Prevalence and Risk Factors of Diabetic Retinopathy: The Singapore Epidemiology of Eye Diseases Study.

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.

Impact of Incidence and Progression of Diabetic Retinopathy on Vision-Specific Functioning.

PURPOSE: To investigate the independent impact of the incidence and progression of diabetic retinopathy (DR) on visual functioning (VF). DESIGN: Population-based cohort study. PARTICIPANTS: A total of 518 participants aged 40 to 80 years (baseline visit 2007-2009 and second visit 6 years later, 2013-2015), with diabetes, clinical data, and VF information at both visits. MAIN OUTCOME MEASURES: VF-7 scores, converted to interval-level person measures (in logits) using Rasch analysis. METHODS: Incident DR was defined using the Modified Airlie House classification as "none or minimal" DR at baseline and at least mild nonproliferative DR at follow-up; incident vision-threatening DR (VTDR; severe nonproliferative DR, proliferative DR, and/or clinically significant macular edema) as no VTDR at baseline, and present at follow-up; and DR progression as at least a 1-step worsening in DR at follow-up from mild or worse status at baseline. The longitudinal associations between incident DR, VTDR, and DR progression, as well as change in composite and individual item scores of VF, were assessed using multivariable linear regression models. RESULTS: Of the 518 participants (mean age ± standard deviation [SD] 59.8±9.0 years; 47.7% female), 42 (9.8%), 14 (2.8%), and 32 (42.7%) had incident DR, incident VTDR, and DR progression, respectively, at follow-up. In models adjusting for traditional confounders, persons with incident DR and VTDR had a 13.7% (ß = -0.60; 95% confidence interval [CI], -0.96 to -0.24; P = 0.001) and 23% (ß = -1.00; 95% CI, -1.61 to -0.38; P = 0.001) reduction in mean VF scores at follow-up. Furthermore, individuals with incident DR had similar independent reductions in scores for 7 individual items of the VF-7, whereas those with incident VTDR had the largest reductions for activities like cooking (31%; P = 0.003), reading the newspaper (29.6%; P < 0.001), and seeing street signs (28%, P = 0.001) at follow-up. Progression of DR was not independently associated with change in overall VF (ß = -0.18; 95% CI, -1.00, 0.64; P = 0.660). CONCLUSIONS: Incident DR, particularly vision-threatening stages, has a substantial negative impact on people's overall vision-dependent functioning and specific activities such as cooking, seeing street signs, and reading the newspaper. Our findings reinforce the need for strategies to prevent or delay the development of DR.

Diet soft drink is associated with increased odds of proliferative diabetic retinopathy.

IMPORTANCE: While consumption of soft drink may increase the risk of cardiovascular disease, the relationship between soft drink consumption and diabetes complications is unknown. BACKGROUND: To explore the association between regular and diet soft drink consumption, and diabetic retinopathy (DR) and diabetic macular oedema (DME). DESIGN: Clinical, cross-sectional study. PARTICIPANTS: Adult patients with diabetes recruited from a tertiary eye hospital (Melbourne, Australia) answered a Food Frequency Questionnaire. METHODS: None, moderate and high soft drink consumption was defined as <1, 1-4 and >4 cans/bottles (375 mL) per week, respectively. Due to missing data, data were imputed using the multiple imputation chained equation procedure. Multivariable logistic regression models determined the associations between soft drink consumption, and presence and severity of DR/DME. MAIN OUTCOME MEASURES: Presence and severity of DR/DME. RESULTS: Of the 609 participants (mean age ± standard deviation: 64.6 ± 11.6 years; males = 210), 285 (46.8%) and 190 (31.2%) consumed diet and regular soft drink, respectively. A total of 230 (37.8%), 36 (5.9%), 154 (25.3%), 28 (4.6%) and 146 (24.0%) had no DR, mild non-proliferative DR (NPDR), moderate NPDR, severe NPDR and proliferative DR (PDR), respectively. High diet soft drink consumption was independently associated with increased likelihood of having PDR (odds ratio = 2.51, 95% confidence interval = 1.05-5.98), compared to no consumption. In contrast, regular soft drink was not associated with DR or DME. CONCLUSIONS AND RELEVANCE: Consuming >4 cans (1.5 L)/week of diet soft drink is associated with a more than twofold risk of having PDR in patients with diabetes. Longitudinal studies are needed to further elucidate the association and its underpinning mechanisms.

Plasma lipoprotein subfraction concentrations are associated with lipid metabolism and age-related macular degeneration.

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.

Type 2 Diabetes Genetic Variants and Risk of Diabetic Retinopathy.

PURPOSE: Genetic association studies to date have not identified any robust risk loci for diabetic retinopathy (DR). We hypothesized that individuals with more diabetes genetic risk alleles have a higher risk of developing DR. DESIGN: Case-control genetic association study. PARTICIPANTS: We evaluated the aggregate effects of multiple type 2 diabetes-associated genetic variants on the risk of DR among 1528 participants with diabetes from the Singapore Epidemiology of Eye Diseases Study, of whom 547 (35.8%) had DR. METHODS: Participants underwent a comprehensive ocular examination, including dilated fundus photography. Retinal photographs were graded using the modified Airlie House classification system to assess the presence and severity of DR following a standardized protocol. We identified 76 previously discovered type 2 diabetes-associated single nucleotide polymorphisms (SNPs) and constructed multilocus genetic risk scores (GRSs) for each individual by summing the number of risk alleles for each SNP weighted by the respective effect estimates on DR. Two GRSs were generated: an overall GRS that included all 76 discovered type 2 diabetes-associated SNPs, and an Asian-specific GRS that included a subset of 55 SNPs previously found to be associated with type 2 diabetes in East and/or South Asian ancestry populations. Associations between the GRSs with DR were determined using logistic regression analyses. Discriminating ability of the GRSs was determined by the area under the receiver operating characteristic curve (AUC). MAIN OUTCOME MEASURES: Odds ratios on DR. RESULTS: Participants in the top tertile of the overall GRS were 2.56-fold more likely to have DR compared with participants in the lowest tertile. Participants in the top tertile of the Asian-specific GRS were 2.00-fold more likely to have DR compared with participants in the bottom tertile. Both GRSs were associated with higher DR severity levels. However, addition of the GRSs to traditional risk factors improved the AUC only modestly by 3% to 4%. CONCLUSIONS: Type 2 diabetes-associated genetic loci were significantly associated with higher risks of DR, independent of traditional risk factors. Our findings may provide new insights to further our understanding of the genetic pathogenesis of DR.

Development and Validation of a Deep Learning System for Diabetic Retinopathy and Related Eye Diseases Using Retinal Images From Multiethnic Populations With Diabetes.

Importance: A deep learning system (DLS) is a machine learning technology with potential for screening diabetic retinopathy and related eye diseases. Objective: To evaluate the performance of a DLS in detecting referable diabetic retinopathy, vision-threatening diabetic retinopathy, possible glaucoma, and age-related macular degeneration (AMD) in community and clinic-based multiethnic populations with diabetes. Design, Setting, and Participants: Diagnostic performance of a DLS for diabetic retinopathy and related eye diseases was evaluated using 494 661 retinal images. A DLS was trained for detecting diabetic retinopathy (using 76 370 images), possible glaucoma (125 189 images), and AMD (72 610 images), and performance of DLS was evaluated for detecting diabetic retinopathy (using 112 648 images), possible glaucoma (71 896 images), and AMD (35 948 images). Training of the DLS was completed in May 2016, and validation of the DLS was completed in May 2017 for detection of referable diabetic retinopathy (moderate nonproliferative diabetic retinopathy or worse) and vision-threatening diabetic retinopathy (severe nonproliferative diabetic retinopathy or worse) using a primary validation data set in the Singapore National Diabetic Retinopathy Screening Program and 10 multiethnic cohorts with diabetes. Exposures: Use of a deep learning system. Main Outcomes and Measures: Area under the receiver operating characteristic curve (AUC) and sensitivity and specificity of the DLS with professional graders (retinal specialists, general ophthalmologists, trained graders, or optometrists) as the reference standard. Results: In the primary validation dataset (n = 14 880 patients; 71 896 images; mean [SD] age, 60.2 [2.2] years; 54.6% men), the prevalence of referable diabetic retinopathy was 3.0%; vision-threatening diabetic retinopathy, 0.6%; possible glaucoma, 0.1%; and AMD, 2.5%. The AUC of the DLS for referable diabetic retinopathy was 0.936 (95% CI, 0.925-0.943), sensitivity was 90.5% (95% CI, 87.3%-93.0%), and specificity was 91.6% (95% CI, 91.0%-92.2%). For vision-threatening diabetic retinopathy, AUC was 0.958 (95% CI, 0.956-0.961), sensitivity was 100% (95% CI, 94.1%-100.0%), and specificity was 91.1% (95% CI, 90.7%-91.4%). For possible glaucoma, AUC was 0.942 (95% CI, 0.929-0.954), sensitivity was 96.4% (95% CI, 81.7%-99.9%), and specificity was 87.2% (95% CI, 86.8%-87.5%). For AMD, AUC was 0.931 (95% CI, 0.928-0.935), sensitivity was 93.2% (95% CI, 91.1%-99.8%), and specificity was 88.7% (95% CI, 88.3%-89.0%). For referable diabetic retinopathy in the 10 additional datasets, AUC range was 0.889 to 0.983 (n = 40 752 images). Conclusions and Relevance: In this evaluation of retinal images from multiethnic cohorts of patients with diabetes, the DLS had high sensitivity and specificity for identifying diabetic retinopathy and related eye diseases. Further research is necessary to evaluate the applicability of the DLS in health care settings and the utility of the DLS to improve vision outcomes.

Interpretation of hip fracture patterns using areal bone mineral density in the proximal femur.

INTRODUCTION: Bone mineral density scans are currently interpreted based on an average score of the entire proximal femur. Improvements in technology now allow us to measure bone density in specific regions of the proximal femur. The study attempts to explain the pathophysiology of neck of femur (NOF) and intertrochanteric/basi-cervical (IT) fractures by correlating areal BMD (aBMD) scores with fracture patterns, and explore possible predictors for these fracture patterns. MATERIALS AND METHODS: This is a single institution retrospective study on all patients who underwent hip surgeries from June 2010 to August 2012. A total of 106 patients (44 IT/basi-cervical, 62 NOF fractures) were studied. The data retrieved include patient characteristics and aBMD scores measured at different regions of the contralateral hip within 1 month of the injury. Demographic and clinical characteristic differences between IT and NOF fractures were analyzed using Fisher's Exact test and two-sample t test. Relationship between aBMD scores and fracture patterns was assessed using multivariable regression modeling. RESULTS: After adjusted multivariable analysis, T-Troc and T-inter scores were significantly lower in intertrochanteric/basi-cervical fractures compared to neck of femur fractures (P = 0.022 and P = 0.026, respectively). Both intertrochanteric/basi-cervical fractures (mean T.Tot -1.99) and neck of femur fractures (mean T.Tot -1.64) were not found to be associated with a mean T.tot less than -2.5. However, the mean aBMD scores were consistently less than -2.5 for both intertrochanteric/basi-cervical fractures and neck of femur fractures. Gender and calcium intake at the time of injury were associated with specific hip fracture patterns (P = 0.002 and P = 0.011, respectively). CONCLUSIONS: Hip fracture patterns following low energy trauma may be influenced by the pattern of reduced bone density in different areas of the hip. Intertrochanteric/basi-cervical fractures were associated with significantly lower T-Troc and T-Inter scores compared to neck of femur fractures, suggesting that the fracture traversed through the areas with the lowest bone density in the proximal femur. In the absence of reduced T.Troc and T.Inter, neck of femur fractures occurred more commonly. T-Total scores may underestimate the severity of osteoporosis/osteopenia and measuring T-score at the neck of femur may better reflect the severity of osteoporosis and likelihood of a fragility fracture.

Bilateral sequential small-incision lenticule extraction and LASIK result in similar short-term quality-of-life outcomes.

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" (ß: -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" (ß: -14.8, 95% CI, -27.9 to -1.7). Emotional well-being (overall), and items "feeling able to do things" (ß: 11.0, 95% CI, 1.6-20.4) and "feeling eager to try new things" (ß: 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.

Relationship between vision impairment and employment.

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.

Combining retinal and choroidal microvascular metrics improves discriminative power for diabetic retinopathy.

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 mm2 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.