Sunny Shen

Bio: Sunny Shen is an academic researcher from National University of Singapore. The author has contributed to research in topics: Population & Orbit (anatomy). The author has an hindex of 13, co-authored 24 publications receiving 1270 citations. Previous affiliations of Sunny Shen include Moorfields Eye Hospital & SingHealth.

Rationale and methodology for a population-based study of eye diseases in Malay people: The Singapore Malay eye study (SiMES).

Abstract: Purpose: Although there are approximately 200 million people of Malay ethnicity living in Asia, the burden and risk factors of blinding eye diseases in this ethnic group are unknown. This study summarizes the rationale and study design of a population-based study of eye diseases among adult Malays in Singapore. Methods: A population-based cross-sectional study of Malays was designed in Singapore. The sampling frame consisted of all Malays aged 40–79 living in designated study areas in southwestern Singapore. From a list of 16,069 names provided by the Ministry of Home Affairs, age-stratified random sampling was used to select 5,600 names (1,400 people from each decade of 40–49, 50–59, 60–69, and 70–79 years). The target sample size for this study was 3,150 persons. Selected individuals were invited to a centralized clinic by letters, telephone calls, and home visits. Participants underwent standardized interview and assessment of blood pressure, anthropometry, presenting and best-corrected visual acuity, ...

The prevalence and types of glaucoma in malay people: the Singapore Malay eye study.

Abstract: PURPOSE. To assess the prevalence and types of glaucoma in an Asian Malay population.METHODS. The Singapore Malay Eye Study is a population-based, cross-sectional survey that examined 3280 (78.7% response) persons aged 40 to 80 years. Participants underwent a standardized clinical examination including slit-lamp biomicroscopy, Goldmann applanation tonometry, and dilated optic disc assessment. Participants who were suspected to have glaucoma also underwent visual field examination (24-2 SITA standard, Humphrey Visual Field Analyzer II), gonioscopy, and repeat applanation tonometry. Glaucoma was defined according to International Society for Geographical and Epidemiologic Ophthalmology criteria.RESULTS. Of the 3280 participants, 150 (4.6%) had diagnosed glaucoma, giving an age- and sex-standardized prevalence of 3.4% (95% confidence interval [CI], 3.3%-3.5%). The age- and sex-standardized prevalence of primary open-angle glaucoma was 2.5% ( 95% CI, 2.4%-2.6%), primary angle-closure glaucoma 0.12% ( 95% CI, 0.10%-0.14%), and secondary glaucoma 0.61% ( 95% CI, 0.59%-0.63%). Of the 150 glaucoma cases, only 12 (8%) had a previous known history of glaucoma. Twenty-seven (18%) eyes had low vision ( based on best corrected visual acuity logarithm of the minimal angle of resolution [logMAR] > 0.30 to = 1.00).CONCLUSIONS. The prevalence of glaucoma among Malay persons 40 years of age and older in Singapore is 3.4%, comparable to ethnic Chinese people in Singapore and other racial/ethnic groups in Asia. As in Chinese, Caucasians, and African people, primary open-angle glaucoma was the main form of glaucoma in this population. More than 90% of glaucoma cases were previously undetected.

Prevalence and causes of low vision and blindness in an urban malay population: the Singapore Malay Eye Study.

Abstract: Objective To describe the prevalence and causes of low vision and blindness in a Malay population. Methods A population-based, cross-sectional study of 3280 participants of Malay ethnicity, aged 40 to 79 years, was conducted. Participants underwent standardized ophthalmic assessments to determine (1) presenting and best-corrected visual acuity according to US and modified World Health Organization definitions of blindness and low vision and (2) the primary causes of visual impairment. Results Of 4168 eligible individuals, 3280 participated in the study (78.7%). The population-weighted prevalence of bilateral blindness was 0.3% and of bilateral low vision, 4.4% (US definition of presenting visual acuity). After best-corrected visual acuity, the population-weighted prevalence of bilateral blindness was reduced to 0.1% and bilateral low vision to 1.0%. Cataract was the main cause of presenting unilateral (38.9%) and bilateral (65.2%) blindness, whereas undercorrected refractive error was the main cause of presenting unilateral (68.8%) and bilateral (52.2%) low vision. Diabetic retinopathy, age-related macular degeneration, and glaucoma were the other leading causes of blindness and low vision. Conclusions The age-standardized prevalences of bilateral blindness and low vision in a Malay population were lower when compared with other Asian studies. Undercorrected refractive error and cataract are the leading causes of visual impairment among the Malay adult population in Singapore.

Determinants of the optic cup to disc ratio in an Asian population: the Singapore Malay Eye Study (SiMES).

Abstract: Objective: To describe the distribution and determinants of the optic cup to disc ratio (CDR) in Malay adults in Singapore.Methods: This population-based, age-stratified study examined 3280 Malay people aged 40 to 80 years in Singapore. Participants underwent a standardized interview and an ocular examination. A slitlamp examination measured the vertical dimensions of the disc and cup, excluding areas of peripapillary atrophy and the Elschnig scleral ring.Results: Vertical CDR was recorded for 3228 right eyes and 3237 left eyes. The mean (SD) CDR was 0.40 (0.15) in both eyes. The CDR in the right eye increased with age (P < .001) and was greater in men vs women (age-adjusted CDR, 0.42 vs 0.39; P < .001). In multiple linear regression, significant determinants of greater CDR were increasing age, male sex, higher intraocular pressure (IOP), lower diastolic blood pressure, lower body mass index, and previous cataract surgery. Of these, higher IOP was the most important determinant of the CDR. After excluding 149 persons with glaucoma, male sex, higher IOP, lower diastolic blood pressure, lower body mass index, and diabetes mellitus were significant predictors of greater CDR.Conclusion: Greater vertical CDR was related to male sex, higher IOP, lower diastolic blood pressure, and lower body mass index.

Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk

Abstract: Blood pressure is a heritable trait(1) influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (>= 140 mm Hg systolic blood pressure or >= 90 mm Hg diastolic blood pressure)(2). Even small increments in blood pressure are associated with an increased risk of cardiovascular events(3). This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention.

A common BIM deletion polymorphism mediates intrinsic resistance and inferior responses to tyrosine kinase inhibitors in cancer.

Abstract: Tyrosine kinase inhibitors (TKIs) elicit high response rates among individuals with kinase-driven malignancies, including chronic myeloid leukemia (CML) and epidermal growth factor receptor-mutated non-small-cell lung cancer (EGFR NSCLC). However, the extent and duration of these responses are heterogeneous, suggesting the existence of genetic modifiers affecting an individual's response to TKIs. Using paired-end DNA sequencing, we discovered a common intronic deletion polymorphism in the gene encoding BCL2-like 11 (BIM). BIM is a pro-apoptotic member of the B-cell CLL/lymphoma 2 (BCL2) family of proteins, and its upregulation is required for TKIs to induce apoptosis in kinase-driven cancers. The polymorphism switched BIM splicing from exon 4 to exon 3, which resulted in expression of BIM isoforms lacking the pro-apoptotic BCL2-homology domain 3 (BH3). The polymorphism was sufficient to confer intrinsic TKI resistance in CML and EGFR NSCLC cell lines, but this resistance could be overcome with BH3-mimetic drugs. Notably, individuals with CML and EGFR NSCLC harboring the polymorphism experienced significantly inferior responses to TKIs than did individuals without the polymorphism (P = 0.02 for CML and P = 0.027 for EGFR NSCLC). Our results offer an explanation for the heterogeneity of TKI responses across individuals and suggest the possibility of personalizing therapy with BH3 mimetics to overcome BIM-polymorphism-associated TKI resistance.

Superpixel Classification Based Optic Disc and Optic Cup Segmentation for Glaucoma Screening

Abstract: Glaucoma is a chronic eye disease that leads to vision loss. As it cannot be cured, detecting the disease in time is important. Current tests using intraocular pressure (IOP) are not sensitive enough for population based glaucoma screening. Optic nerve head assessment in retinal fundus images is both more promising and superior. This paper proposes optic disc and optic cup segmentation using superpixel classification for glaucoma screening. In optic disc segmentation, histograms, and center surround statistics are used to classify each superpixel as disc or non-disc. A self-assessment reliability score is computed to evaluate the quality of the automated optic disc segmentation. For optic cup segmentation, in addition to the histograms and center surround statistics, the location information is also included into the feature space to boost the performance. The proposed segmentation methods have been evaluated in a database of 650 images with optic disc and optic cup boundaries manually marked by trained professionals. Experimental results show an average overlapping error of 9.5% and 24.1% in optic disc and optic cup segmentation, respectively. The results also show an increase in overlapping error as the reliability score is reduced, which justifies the effectiveness of the self-assessment. The segmented optic disc and optic cup are then used to compute the cup to disc ratio for glaucoma screening. Our proposed method achieves areas under curve of 0.800 and 0.822 in two data sets, which is higher than other methods. The methods can be used for segmentation and glaucoma screening. The self-assessment will be used as an indicator of cases with large errors and enhance the clinical deployment of the automatic segmentation and screening.