Retinal ganglion cell neuronal damage in diabetes and diabetic retinopathy.

BACKGROUND: To examine the association of diabetes and diabetic retinopathy (DR) with retinal ganglion cell (RGC) loss. DESIGN: Observational case-control study. PARTICIPANTS: Type 2 diabetes cases and age-gender matched controls without diabetes. METHODS: Spectral-domain optical coherence tomography (OCT) parameters of RGCs were calculated after automated segmentation of macular scans. DR severity was graded on fundus photographs using the modified Airlie House Classification system. Generalized estimating equation was used to compare OCT parameters between cases and controls, adjusted for covariates. MAIN OUTCOME MEASURES: Average ganglion cell-inner plexiform layer (GC-IPL) and average retinal nerve fibre layer (RNFL) thicknesses. RESULTS: We analyzed 227 cases and 227 controls. The mean age (years) of cases was 58.3 and controls was 58.1 (P = 0.13). Among cases, 101 had none, 25 had mild and 101 had moderate or severe DR. Compared with controls, GC-IPL and RNFL were thinner in all cases [mean difference (95% confidence interval [CI]): GC-IPL -4.49 µm (-2.92; -6.06), RNFL -0.93 µm (-0.09; -1.85)], including cases with no DR [mean difference (95% CI), GC-IPL -4.37 µm (-2.72; -6.02), RNFL -1.06 µm (-0.10; -2.02)]. Cases with any DR had thinner GC-IPL than controls [mean difference (95% CI): GC-IPL -4.81 µm (-2.12; -7.50)]. Among cases, subjects with moderate or severe DR had thinner GC-IPL than subjects with no DR [mean difference (95% CI): GC-IPL -2.07 µm (-0.08; -4.07)]. CONCLUSIONS: RGC loss is present in subjects with diabetes and no DR, and is progressive in moderate or severe DR. RGC neuronal damage in diabetes and DR can be clinically detected using OCT.

Glaucoma and associated visual acuity and field loss significantly affect glaucoma-specific psychosocial functioning.

OBJECTIVE: To examine the impact of glaucoma and visual acuity (VA) and visual field (VF) losses on psychosocial functioning (PF). DESIGN: Cross-sectional study. PARTICIPANTS: We compared PF between 192 participants with bilateral glaucoma with VA or VF losses and 40 controls from a tertiary eye hospital clinic in Singapore. METHODS: Glaucoma was defined using the Hodapp-Anderson-Parish criteria. Four psychosocial outcomes of the Glaucoma Quality of Life 36 questionnaire were psychometrically assessed using Rasch analysis. Multivariate regression was performed to determine the independent impact of glaucoma and VA and VF losses on PF. The impact of VA and VF on PF were evaluated by restricted cubic spline analysis. MAIN OUTCOME MEASURES: Anxiety, self-image, psychological well-being, and confidence in health care. RESULTS: The mean age of participants was 66.2±11.0 years, and 63% were male. In the better eye, VA and mean deviation were Snellen 20/25 and -8.89±6.52 dB, respectively. In multivariate models, glaucoma patients had 63.0% greater anxiety (95% confidence interval [CI], -66.0% to -61.2%; P<0.001), 71.0% lower self-image (95% CI, -74.1% to -68.5%; P<0.001), 38.3% less psychological well-being (95% CI, -37.4% to -39.0%; P<0.001), and 32.4% reduced confidence in health care than patients without glaucoma. The worst VA and VF categories had the most reduced PF (range, 26.0% to 81.5%; P<0.001 for all associations) compared with controls. With worsening VA, there was a linear increase in anxiety (P=0.009) and decrease in self-image (P=0.005). With worsening VF from 0 to -12.1 dB (P=0.003), anxiety increased before plateauing. Self-image decreased as VF worsened from 0 to -10 dB (P<0.001), and confidence in health care decreased when VF worsened from 0 to -9.3 dB (P=0.008). However, self-image and confidence in health care actually improved at greater levels of VF loss beyond these thresholds. CONCLUSION: Glaucoma negatively affects PF. Early stage glaucoma with mild VF loss adversely affects anxiety, self-image, and confidence in health care. As VA worsens in advanced glaucoma, anxiety further increases and self-image deteriorates. Ophthalmologists and glaucoma patients need to be aware that both VA and VF losses at different stages of glaucoma negatively impact PF.

Strategies for the modulation of phase II metabolism in a series of PKCε inhibitors.

Extensive phase II metabolism of an advanced PKCε inhibitor resulted in sub-optimal pharmacokinetics in rat marked by elevated clearance. Synthesis of the O-glucuronide metabolite as a standard was followed by three distinct strategies to specifically temper phase II metabolic degradation of the parent molecule. In this study, it was determined that the introduction of proximal polarity to the primary alcohol generally curbed O-glucuronidation and improved PK and physical chemical properties while maintaining potency against the target. Utilization of a Jacobsen hydrolytic kinetic resolution to obtain optically enriched final compounds is also discussed.

Marital status and its relationship with the risk and pattern of visual impairment in a multi-ethnic Asian population.

BACKGROUND: To examine whether marital status is a significant determinant of visual impairment (VI) in urban multi-ethnic Asian population. METHODS: We conducted a population-based study of Singapore-resident ethnic Malays, Indians and Chinese aged ≥40 years. Ophthalmic examination included the assessment of presenting and best-corrected visual acuity (PVA and BCVA) using standardized procedures. Information regarding marital status and socioeconomic status were obtained from an interviewer-administered questionnaire. RESULTS: Among the 10 033 participants, 7756 (77.3%) were married; 589 (5.9%) were single; 407 (4.1%) were separated and 1265 (12.6%) were widowed. Being single (never married) or widowed were significantly associated with best-corrected VI (BCVA < 20/40) and presenting VI (PVA < 20/40) (odds ratios: 1.37-1.59) compared with married people even after adjustment for age, sex and socioeconomic status. A marginal prediction model showed that the negative effect of unmarried status on VI increased with age and was stronger among Malays and Indians, but the influence did not vary with gender, educational level and diabetic status. CONCLUSIONS: Unmarried status is associated with VI, particularly among elderly Malays and Indians. Our findings suggest that single and widowed adults may benefit from specific social support and eye care programmes.

Ethnic differences in undercorrected refractive error in Asians.

PURPOSE: To describe the ethnic variations in the prevalence and risk factors for undercorrected refractive error and its impact on vision-specific functioning (VF) in a multiethnic Asian population. METHODS: A total of 3353 Chinese, 3400 Indians, and 3280 Malays in Singapore participated in this population-based cross-sectional study. Distance presenting visual acuity (VA) was measured using a logarithm of the minimum angle of resolution number chart. Best-corrected VA was assessed using the same test protocol as presenting VA. Undercorrected refractive error was defined as an improvement of at least 0.2 logarithm of the minimum angle of resolution (two lines equivalent) in the best-corrected VA compared with the presenting VA in the better eye when presenting VA was less than 20/40 in the better eye. The VF-11 questionnaire measured participants' VF. Multivariate linear regression was performed to assess the impact of undercorrected refractive error on the overall VF score. RESULTS: Regardless of ethnicity, participants with undercorrected refractive error had a reduction in VF score compared to those with normal vision in both eyes. The overall prevalence of undercorrected refractive error was highest in Indians (25.1%), followed by Malays (22.2%) and Chinese (19.7%). Undercorrected refractive error was less common in spectacles or contact lenses wearers than in non-spectacle wearers or non-contact lenses wearers. Adults with mild to moderate refractive errors were most likely to have undercorrected refractive error (p < 0.001). In multivariate analysis, increasing age (p < 0.001), Indian race (p < 0.001), lower education level (p < 0.001) or poorer housing (p < 0.001), having refractive errors (p < 0.001), and not wearing optical corrections (p < 0.001) were significantly associated with increasing undercorrected refractive error. CONCLUSIONS: In Singapore, undercorrected refractive error is most prevalent in Indians and least prevalent in Chinese. The impact of undercorrected refractive error on VF was consistent across all three ethnicities. There may be higher barriers to visual correction among Malays or Indians compared with Chinese in Singapore.

The role of risk tools in diagnosing cancer in primary care.

BACKGROUND: Diagnosing cancer on the basis of a patient's symptoms and risk factors is a core role for general practice. Equally, as part of a cost-effective health system, GPs should avoid over-investigation or referral of patients who are very unlikely to have cancer. Diagnosing cancer in primary care is not straightforward because many of the symptoms of cancer have more common benign causes. OBJECTIVE: The aim of this article is to review the use of risk tools for diagnosing cancer in primary care. DISCUSSION: Certain cancers, such as lung, pancreas, ovary and myeloma, are particularly challenging to diagnose early. National guidelines exist to support identification of patients who are more likely to have an undiagnosed cancer but these list single symptoms as so-called 'red flags'. Validated risk tools, developed in general practice, exist that predict cancer diagnosis on the basis of patterns of symptoms and risk factors. These tools might prove useful in supporting cancer diagnosis in general practice and also reducing investigation of patients at very low risk of cancer.

Vision impairment and major causes of vision loss impacts on vision-specific functioning independent of socioeconomic factors.

PURPOSE: To quantify the eye disease-specific impact of unilateral and bilateral vision impairment (VI) on vision-specific functioning (VF). DESIGN: The Singapore Indian Eye population-based study. PARTICIPANTS: Ethnic Indians older than 40 years of age living in Singapore. METHODS: Participants underwent standardized ophthalmic assessments for VI and blindness, defined using presenting visual acuity (United States definition). Sociodemographic data were recorded using a standardized questionnaire. Rasch analysis was used to validate the Visual Function Index 11 and to determine its psychometric properties. The major causes of VI (i.e., cataract, refractive error, age-related macular degeneration, diabetic retinopathy [DR], and glaucoma) were determined by ophthalmologists on examination. Multivariate linear regression analysis was performed to assess the impact of VI on the overall VF Rasch score. MAIN OUTCOME MEASURES: Vision-specific functioning. RESULTS: Three thousand three hundred ninety-six persons were analyzed. Participants with VI had a systematic reduction in VF score compared with those with normal vision in both eyes, ranging from -11.2% normal vision in one eye and low vision in the other eye (95% confidence interval [CI], -12.2% to -10.3%; P<0.001), to -12.7% blindness in one eye and normal vision in the other eye (CI, -15.1% to -10.4%; P<0.001), to -19.4% low vision in both eyes (CI, -20.8% to -18.1%; P<0.001), to -52.9% blindness in one eye and low vision in other eye (CI, -55.3% to -50.4%; P<0.001), to -77.2% blindness in both eyes (CI, -82.4% to 72.0%; P<0.001). The impact of VI on VF score varied across different major causes of vision loss, regardless of socioeconomic factors. Vision impairment attributed to cataract in one or both eyes had a significant decrease in VF score by 17.7% and 22.3%, respectively, compared with those with normal vision in both eyes (P<0.001). The impact of unilateral and bilateral VI on VF score was greater in participants with glaucoma (32.2% in unilateral cases and 35.9% in bilateral cases; P<0.001) and DR (29.4% in unilateral cases and 33.3% in bilateral cases; P<0.001). CONCLUSIONS: Vision impairment and major age-related eye diseases such as cataract, DR, and glaucoma are associated significantly with worse deterioration in VF, regardless of education level, literacy adequacy, or immigration pattern. Glaucoma and DR seemed to have a greater negative impact on VF score compared with cataract. This study highlights the importance of disease-specific interventions in reducing the adverse impact of VI on daily activities.

Cardio-metabolic risk factors and prehypertension in persons without diabetes, hypertension, and cardiovascular disease.

BACKGROUND: Prehypertension has been shown to be an early risk factor of cardiovascular disease (CVD). We investigated the prevalence and pattern of cardiometabolic risk factors in prehypertension in three ethnic Asian populations in Singapore. METHODS: We examined data from Chinese (n=1177), Malay (n=774), and Indian (n=985) adults aged 40-80 years who participated in three independent population based studies conducted from 2004-2011 in Singapore who were free of diabetes, hypertension and previous CVD. Prehypertension was defined as systolic blood pressure (BP) 120-139 mm Hg or diastolic BP 80-89 mm Hg. Random blood glucose, glycated haemoglobin (HbA1c), body mass index (BMI), triglycerides, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol were examined as indicators of adverse cardiometabolic profile. The association between metabolic variables and prehypertension was examined using logistic regression models adjusting for potential confounders. RESULTS: The prevalence of prehypertension was 59.8% (Chinese), 68.9% (Malays) and 57.7% Indians. Higher levels of blood glucose, HbA1c and BMI were significantly associated with prehypertension in all three ethnic groups, odds ratio (95% confidence interval) of prehypertension in Chinese, Malays and Indians were: 1.42 (1.10, 1.83), 1.53 (1.05, 2.24), 1.49 (1.13, 1.98) for high-glucose; 3.50 (1.01, 12.18), 3.72 (1.29, 10.75), 2.79 (1.31, 5.94) for high-HbA1c; 1.86 (1.34, 2.56), 2.96 (2.10, 4.18), 1.68 (1.28, 2.20) for high-BMI. In addition, higher levels of LDL cholesterol in Chinese and higher levels of triglycerides were significantly associated with prehypertension. These associations persisted when metabolic variables were analysed as continuous variables. CONCLUSIONS: Higher levels of blood glucose, HbA1c and BMI were associated with prehypertension in all three ethnic groups in Singapore. Screening for prehypertension and lifestyle modifications could potentially reduce the burden of CVD in otherwise healthy Asian adults living in Singapore.

Application of a high-resolution in vitro human MDR1-MDCK assay and in vivo studies in preclinical species to improve prediction of CNS drug penetration.

P-glycoprotein (P-gp, MDR1) is expressed at the blood-brain barrier (BBB) and restricts penetration of its substrates into the central nervous system (CNS). In vitro MDR1 assays are frequently used to predict the in vivo relevance of MDR1-mediated efflux at the BBB. It has been well established that drug candidates with high MDR1 efflux ratios (ERs) display poor CNS penetration. Following a comparison of MDR1 transporter function between the MDR1-MDCKI cell line from National Institutes of Health (NIH) and our internal MDR1-MDCKII cell line, the former was found to provide better predictions of in vivo brain penetration than our in-house MDR1-MDCKII cell line. In particular, the NIH MDR1 assay has an improved sensitivity to differentiate the compounds with ERs of <3 in our internal cell line and is able to reduce the risk of false negatives. A better correlation between NIH MDR1 ERs and brain penetration in rat and non-human primate (NHP) was demonstrated. Additionally, a comparison of brain penetration time course of MDR1 substrates and an MDR1 non-substrate in NHP demonstrated that MDR1 interaction can delay the time to equilibrium of drug concentration in the brain with plasma. It is recommended to select highly permeable compounds without MDR1 interaction for rapid brain penetration to produce the maximal pharmacological effect in the CNS with a quicker onset.

The impact of the severity of vision loss on vision-specific functioning in a German outpatient population - an observational study.

BACKGROUND: To validate the German-translated VF-14, a vision-specific scale, and determine the relationship between the severity of vision impairment, ocular conditions, and visual functioning. METHODS: This was a clinic-based, cross-sectional study with 184 patients with low vision and 90 normal-sighted controls recruited from a German eye hospital. Participants underwent a clinical examination and completed the German VF-14 scale. The validity of the VF-14 scale was assessed using Rasch analysis. The main outcome measure was the visual functioning overall score. RESULTS: The participants' mean ± SD [standard deviation] age was 59.4 ± 21.8 years ,and there were more female (58.4%) than male participants. The main cause of vision loss was age-related macular degeneration [AMD] (n = 54, 19.7%). Rasch analysis substantiated the German VF-14 to be a valid scale to assess visual functioning in the sample. Visual functioning consistently declined with worsening vision. In adjusted-multivariate analysis models, compared to control participants, those with mild, or moderate/severe vision impairment recorded significantly poorer visual functioning scores (p < 0.05). The independent association was clinically significant for those with moderate/severe vision impairment. The main ocular conditions were also found to be independently associated with worse visual functioning, with clinical significance found for AMD, diabetic retinopathy, and other retinal diseases. CONCLUSIONS: Using a psychometrically valid German-translated VF-14, even mild vision impairment was independently associated with poor visual functioning. These findings reinforce the importance of early preventative and rehabilitative efforts to prevent longitudinal deterioration in vision loss.

Shared Care for Patients with Diabetes at Risk of Retinopathy: A Feasibility Trial.

PURPOSE: While diabetes is a chronic disease, in many health care systems patients with diabetes at risk of diabetic retinopathy (DR) are managed in hospital settings. Aim of this feasibility study is to assess the quality of care and economic benefits of a shared care model managing patients at risk of DR in a primary eye care clinic (PEC) compared with a current tertiary specialist outpatient clinic (SOC). METHODS: A randomized trial was performed, to compare a PEC with a SOC in Singapore. The trial patients included those previously seen at the SOC, and having no DR or stable mild non proliferative (NPDR) with no macular edema, no visual and DR deterioration. Primary outcomes were clinical management. Secondary outcomes were patient satisfaction and cost of consultation. Differences analysis used equivalence testing and generalized odds ratios (GOR). RESULTS: The trial included 231 patients, 83.1% classified as no DR (PEC: 79.1%; SOC: 87.1%) and 16.9% as stable mild NPDR (PEC: 20.9%; SOC: 12.9%). DR management at PEC was significantly equivalent to that received at the SOC (rate difference 2.56%; CI: (-1.61% to 6.74%)) and 4.29%; CI: (0.14%-8.45%), respectively. Patient satisfaction at the PEC was equally high when compared to SOC (GOR: 1.71; CI: (0.50-2.00)). Direct costs per patient visit was 45% lower at PEC compared to SOC. CONCLUSIONS: Our feasibility trial showed that patients with diabetes with no or stable DR receive similar clinical care and management at a lower-cost PEC setting, are equally satisfied with the service compared to tertiary eye care. A follow-up study is necessary to validate these findings. Managing patients with diabetes at risk of DR at a PEC may be a safe and effective shared care model to improve accessibility for patients while enhancing professional collaboration between hospital and community settings.

Effectiveness of the "living successfully with low vision" self-management program: Results from a randomized controlled trial in Singaporeans with low vision.

OBJECTIVE: To determine the effectiveness of the "Living Successfully with Low Vision" (LSLV) self-management program to improve patient-reported outcomes in Singaporeans. METHODS: In this randomized controlled trial, 165 participants with low vision (LV) were recruited and assigned to usual care (LV aid training only; N = 82) or LSLV program (N = 83). The LSLV program focuses on problem solving, coping mechanism and anticipation/preparation for future needs. The primary outcome was vision-related quality of life (VRQoL; measured using the Impact of Vision Impairment [IVI] questionnaire), while secondary outcomes included health-related quality of life; mental health; and self-efficacy, assessed at baseline, 2-weeks and 6-months post-intervention. Within- and between-group comparisons were conducted using paired t-tests and repeated measures analysis of covariance, respectively. RESULTS: A total of 128 individuals (77.6%) completed all assessments. At 2 weeks, LSLV participants alone experienced a significant within-group improvement in the mean IVI Emotional score (P = 0.05) but not at 6 months. No other within- or between-group effects were observed. CONCLUSION: While SM programs have shown promising results in the management of many chronic diseases, our findings suggest that the LVSM program was not an effective approach for LV rehabilitation in Singapore. PRACTICE IMPLICATION: Other evidence-based strategies to improve QoL in patients with LV may be warranted.

Dry Eye-Related Visual Blurring and Irritative Symptoms and Their Association with Depression and Anxiety in Eye Clinic Patients.

PURPOSE: Dry eye is a common condition known to have many systemic co-morbidities. We aim to report the frequency of depression and anxiety suspects in eye clinic patients and explore the association between dry eye signs and symptoms with depression and anxiety. MATERIALS AND METHODS: Adult outpatients were recruited from dry a public tertiary ophthalmology specialist center. Participants underwent socio-demographic and dry eye symptoms questionnaires, fluorescein dye tear break-up time (TBUT), fluorescein dye corneal staining and Schirmer's test. Rasch analysis was used to internally validate the Hospital Anxiety and Depression Scale (HADS) and the Center for Epidemiologic Studies Depression Scale (CES-D) and determine its psychometric properties. RESULTS: A total of 96 participants (mean age 54.5 ± 10.8; 64.1% women) were recruited. The mean score for the CES-D was 12.1 ± 9.8 with 28 participants (31.5%) having a score of above 16 (published threshold). The mean score for depression-associated questions in the HADS was 3.6 ± 3.6 with 13 participants (14.1%) having a score ≥8. The mean score for the anxiety-associated questions in the HADS was 5.3 ± 3.6 with 24 participants (26.1%) having score ≥8. There was a weak inverse correlation between Schirmer's test and CES-D scores. Elevated depression scores from the CES-D were significantly associated with visual blurring but not irritation, in dry eye patients with low TBUT. CONCLUSIONS: In conclusion, specific types of dry eye symptoms, particularly those with increased frequency of visual blurring were associated with symptoms of depression. The optical aberrations induced by dry eye, associated with tear instability, may predispose to depressive tendency.

Differential Association of Generalized and Abdominal Obesity With Diabetic Retinopathy in Asian Patients With Type 2 Diabetes.

IMPORTANCE: The association between obesity and diabetic retinopathy (DR) is equivocal, possibly owing to the strong interrelation between generalized and abdominal obesity leading to a mutually confounding effect. To our knowledge, no study in Asia has investigated the independent associations of these 2 parameters with DR to date. OBJECTIVE: To investigate the associations of generalized (defined by body mass index [BMI], calculated as weight in kilograms divided by height in meters squared) and abdominal obesity (assessed by waist to hip ratio [WHR]) with DR in a clinical sample of Asian patients with type 2 diabetes mellitus. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional clinic-based study was conducted at the Singapore National Eye Centre, a tertiary eye care institution in Singapore, from December 2010 to September 2013. We recruited 498 patients with diabetes. After exclusion of participants with ungradable retinal images and type 1 diabetes, 420 patients (mean [SD] age, 57.8 [7.5] years; 32.1% women) were included in the analyses. EXPOSURES: Body mass index and WHR as waist/hip circumference (in centimeters). MAIN OUTCOMES AND MEASURES: The presence and severity of DR were graded from retinal images using the modified Airlie House Classification into none (n = 189), mild-moderate (Early Treatment Diabetic Retinopathy Study scale score, 20-41; n = 125), and severe DR (Early Treatment Diabetic Retinopathy Study scale score ≥53; n = 118). The associations of BMI and WHR with DR were assessed using multinomial logistic regression models adjusting for age, sex, traditional risk factors, and mutually for BMI and WHR. RESULTS: Among the total of 420 patients, the median (interquartile range) for BMI and WHR were 25.7 (5.7) and 0.94 (0.08), respectively. In multivariable models, BMI was inversely associated with mild-moderate and severe DR (odds ratio [OR], 0.90 [95% CI, 0.84-0.97] and OR, 0.92 [95% CI, 0.85-0.99] per 1-unit increase, respectively), while WHR was positively associated with mild-moderate and severe DR (OR, 3.49 [95% CI, 1.50-8.10] and OR, 2.68 [95% CI, 1.28-5.62] per 0.1-unit increase, respectively) in women (P for interaction = .006). No sex-specific associations were found between BMI and DR (P for interaction >.10). CONCLUSIONS AND RELEVANCE: In Asian patients with type 2 diabetes, a higher BMI appeared to confer a protective effect on DR, while higher WHR was associated with the presence and severity of DR in women. Our results may inform future clinical trials to determine whether WHR is a more clinically relevant risk marker than BMI for individuals with type 2 diabetes.

A randomised controlled trial of a self-management programme for low vision implemented in low vision rehabilitation services.

OBJECTIVE: To investigate the effectiveness of a low vision self-management programme (LVSMP) in older adults. METHODS: Participants (n=153) were existing clients of a national low vision rehabilitation organisation randomly allocated to usual services (n=60) or usual services plus LVSMP (n=93). The LVSMP was an 8-week group programme facilitated by low vision counsellors. The primary outcome was vision-specific quality of life (QoL) measured using the Impact of Vision Impairment (IVI) questionnaire. Secondary outcomes emotional well-being, self-efficacy and adaptation to vision loss were measured using the depression, anxiety, stress scale (DASS), general self-efficacy scale (GSES), and short form adaptation to age-related vision loss scale (AVL12). RESULTS: At one and six month follow-up assessments, no significant between-group differences were found for vision-specific QoL, emotional well-being, adaptation to vision loss or self-efficacy (p>0.05). Univariate and multivariate analyses revealed no impact of the intervention on outcome measures. CONCLUSIONS: In contrast to previous work, our study found limited benefit of a LVSM programme on QoL for older adults accessing low vision services. PRACTICE IMPLICATIONS: When implementing self-management programmes in low vision rehabilitation settings, issues of client interest, divergence of need, programme accessibility and fidelity of intervention delivery need to be addressed.

Identification of novel HSP90α/ß isoform selective inhibitors using structure-based drug design. demonstration of potential utility in treating CNS disorders such as Huntington's disease.

A structure-based drug design strategy was used to optimize a novel benzolactam series of HSP90α/ß inhibitors to achieve >1000-fold selectivity versus the HSP90 endoplasmic reticulum and mitochondrial isoforms (GRP94 and TRAP1, respectively). Selective HSP90α/ß inhibitors were found to be equipotent to pan-HSP90 inhibitors in promoting the clearance of mutant huntingtin protein (mHtt) in vitro, however with less cellular toxicity. Improved tolerability profiles may enable the use of HSP90α/ß selective inhibitors in treating chronic neurodegenerative indications such as Huntington's disease (HD). A potent, selective, orally available HSP90α/ß inhibitor was identified (compound 31) that crosses the blood-brain barrier. Compound 31 demonstrated proof of concept by successfully reducing brain Htt levels following oral dosing in rats.

Lack of awareness of common eye conditions in the community.

PURPOSE: Awareness of eye conditions aids health promotion activities and leads to better outcomes. We examined factors influencing the lack of awareness of common eye conditions in a population. METHODS: The Singapore Malay Eye Study examined 3280 (78.7% response) Malays aged 40-80 years. We included 2112 (64.4%) participants with at least one of five eye conditions: 1504 (71.2%) with cataract, 1013 (47.8%) with myopia, 270 (12.8%) with diabetic retinopathy, 181 (8.6%) with age-related macular degeneration and 150 (7.1%) with glaucoma. Lack of awareness was defined in the questionnaire as not answering "yes" to previously being told by a doctor of having the eye condition. RESULTS: Among 2112 participants, 83.2% were unaware of at least one of their eye conditions. After controlling for age, sex and socioeconomic factors, participants unaware of their eye condition were older (odds ratio, OR, 1.03, per 1 year, p < 0.001), had better visual acuity (OR 1.32, p = 0.04), lower education (OR 1.89, p < 0.001), poorer literacy (OR 1.44, p = 0.02), lower income (OR 1.73, p = 0.009), higher blood glucose (OR 1.08, per 1 mmol/L, p < 0.001), higher serum cholesterol (OR 1.20, per 1 mmol/L, p = 0.003), lower annual eye examination attendance (OR 2.08, p < 0.001) and were less likely to wear glasses (OR 2.90, p < 0.001) than those who were aware of their condition. CONCLUSIONS: In this community-based population, 80% of those with common eye conditions were unaware of their condition.

Impact of glaucoma severity and laterality on vision-specific functioning: the Singapore Malay eye study.

PURPOSE: We determined the impact of glaucoma severity and laterality on vision-specific functioning (VF) in an Asian population. METHODS: The Singapore Malay Eye Study (SiMES) was a population-based cross-sectional study of 3280 Malays aged 40 to 80 years. VF was assessed using the VF-11 questionnaire. Associations between VF-11 score and glaucoma clinical indices (glaucoma severity in better and worse eyes, and laterality) were determined by multivariate regression modeling. Glaucoma severity was defined as mild, moderate, advanced, and severe based on the Hodapp-Anderson-Parish system. Rasch analysis was used to validate the VF-11 and determine its psychometric properties. RESULTS: Of 926 persons analyzed, 123 had glaucoma (13.3% glaucoma prevalence in analyzed sample). The mean ± SD VF score was 3.64 ± 1.05 log of odds units (Logits). In multivariate models adjusting for sociodemographic, ocular, and systemic variables, poorer VF was associated with increasingly worse eye visual field loss (ß = 0.016, 95% confidence interval [CI] 0.004-0.029, P < 0.001), but not that of the better eye (P > 0.05). Compared to controls, VF was reduced in individuals with worse eye advanced and severe glaucoma (ß = -0.65, 95% CI -1.03 to -0.28, P < 0.05), but not mild or moderate glaucoma (P > 0.05). Compared to controls, VF was reduced in unilateral (ß = -0.29, 95% CI -0.54 to -0.04, P < 0.05), but not bilateral glaucoma (P > 0.05). These associations remained significant after adjusting for presenting and best-corrected visual acuity. CONCLUSIONS: Among Singaporean Malays, unilateral, and advanced and severe glaucoma in the worse eye significantly impacts on VF. Identifying early-stage glaucoma, preventing progression, and visual rehabilitation in advanced glaucoma are important aspects of glaucoma management.

How much eye care services do Asian populations need? Projection from the Singapore Epidemiology of Eye Disease (SEED) study.

PURPOSE: We quantified and measured the needs for specific eye care services, including refractive services (RS), annual eye examination services (AES), cataract surgery services (CSS), and low vision services (LVS) in urban adult populations in Asia. METHODS: We conducted three population-based studies of Singapore-resident Chinese, Malays, and Indians aged ≥40 years to measure the proportion of people who needed specific eye care services. RESULTS: Our data included 3353 Chinese, 3280 Malays, and 3400 Indians (participation rate 73.6%). Overall, approximately 70% of the populations needed eye care services and more than 30% had more than one need. The age-standardized proportion of people who need RS, AES, CSS, and LVS were 65.3%, 22.4%, 12.5%, and 0.5%, respectively, in Chinese. These figures were 49.6%, 33.6%, 11.0%, and 0.7%, respectively, in Malays, and 55.6%, 40.0%, 13.4%, and 0.8%, respectively, in Indians. With demographic change, our projection showed that the number of adults needing eye care services in urban Asia will grow from 437 million in 2010 to 827 million in 2030. Diabetes was a major cause of AES and a significant predictor for CSS, whereas higher blood pressure was a predictor for AES. CONCLUSIONS: The needs for eye care services in an urban setting in Asia is high, particularly the needs for RS, AES, and CSS. The high prevalences of diabetes and hypertension are the driving factors underlying these needs. The burden of providing such eye care services highlights the need for new strategies for improvements in primary care and capacity building for eye care professionals other than ophthalmologists.

Critical issues in implementing low vision care in the Asia-Pacific region.

Two-thirds of the world's population with low vision resides in the Asia-Pacific region. Provision of comprehensive low vision services is important to improve vision-related quality of life (QoL) for people with this condition. This review outlines the critical issues and challenges facing the provision of low vision services in the Asia-Pacific region. The review offers possible strategies to tackle these issues and challenges facing service providers and policy makers in lieu of Vision 2020 strategies in this area. Pertinent findings from the global survey of low vision services and extensive ground work conducted in the region are used; in addition, a discussion on the availability of services, human resources and training, and funding and the future sustainability of low vision care will be covered. In summary, current issues and challenges facing the region are the lack of specific evidence-based data, access, appropriate equipment and facilities, human resources, funding, and sustainability. These issues are inextricably interlinked and thus cannot be addressed in isolation. The solutions proposed cover all areas of the VISION 2020 strategy that include service delivery, human resources, infrastructure and equipment, advocacy and partnership; and include provision of comprehensive care via vertical and horizontal integration; strengthening primary level care in the community; providing formal and informal training to enable task shifting and capacity building; and promoting strong government and private sector partnership to achieve long-term service financial sustainability.