Gemmy Cheung

Diabetic retinopathy: global prevalence, major risk factors, screening practices and public health challenges: a review

Diabetes retinopathy (DR) is a leading cause of vision loss in middle-aged and elderly people globally. Early detection and prompt treatment allow prevention of diabetes-related visual impairment. Patients with diabetes require regular follow-up with primary care physicians to optimize their glycaemic, blood pressure and lipid control to prevent development and progression of DR and other diabetes-related complications. Other risk factors of DR include higher body mass index, puberty and pregnancy, and cataract surgery. There are weaker associations with some genetic and inflammatory markers. With the rising incidence and prevalence of diabetes and DR, public health systems in both developing and developed countries will be faced with increasing costs of implementation and maintenance of a DR screening program for people with diabetes. To reduce the impact of DR-related visual loss, it is important that all stakeholders continue to look for innovative ways of managing and preventing diabetes, and optimize cost-effective screening programs within the community.Diabetes retinopathy (DR) is a leading cause of vision loss in middle‐aged and elderly people globally. Early detection and prompt treatment allow prevention of diabetes‐related visual impairment. Patients with diabetes require regular follow‐up with primary care physicians to optimize their glycaemic, blood pressure and lipid control to prevent development and progression of DR and other diabetes‐related complications. Other risk factors of DR include higher body mass index, puberty and pregnancy, and cataract surgery. There are weaker associations with some genetic and inflammatory markers. With the rising incidence and prevalence of diabetes and DR, public health systems in both developing and developed countries will be faced with increasing costs of implementation and maintenance of a DR screening program for people with diabetes. To reduce the impact of DR‐related visual loss, it is important that all stakeholders continue to look for innovative ways of managing and preventing diabetes, and optimize cost‐effective screening programs within the community.

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.

Hyperopic refractive error and shorter axial length are associated with age-related macular degeneration: the Singapore Malay Eye Study.

PURPOSE To describe the association between refractive errors, ocular biometry, and age-related macular degeneration (AMD) in an Asian Malay population in Singapore. METHODS A population-based study of 3280 Malay individuals aged 40 to 80 years was conducted in Singapore. Early- and late-AMD signs were graded from retinal photographs according to the Wisconsin grading system. Autorefraction, followed by subjective refraction, was performed to obtain spherical equivalent refraction (SER) in diopters, with emmetropia defined as SER -0.5 to +0.5 D, hyperopia as > +0.5 D, and myopia as < -0.5 D. Partial coherence laser interferometry was used to measure axial length, anterior chamber depth, and corneal curvature. The association between refractive status, ocular biometry and the prevalence of both early and late AMD were analyzed. RESULTS Hyperopic refractive error (odds ratio [OR] 1.54; 95% confidence interval [CI] 1.00-2.36; compared with myopia, P = 0.05), shorter axial length (OR, 1.91; CI, 1.05-3.46, comparing 1st vs. 4th quartiles; P = 0.03), and steeper corneal curvature (OR, 1.93; CI, 1.16-3.20, comparing 1st vs. 4th quartiles, P = 0.01) were significantly associated with early AMD, after adjustment for age, sex, smoking, education, height, and systolic blood pressure. Each diopter increase in hyperopic refraction and each millimeter decrease in axial length was associated with an 8% (OR, 1.08; CI, 1.01-1.16; P = 0.03) and 29% (OR, 1.29; CI, 1.06-1.57; P = 0.01) increased risk of early AMD, respectively. No significant association was noted of refractive error and ocular biometry with late AMD. CONCLUSIONS Hyperopic refractive error and shorter axial length are associated with early AMD in Asian eyes.

Diabetic macular oedema

Diabetic macular oedema, characterised by exudative fluid accumulation in the macula, is the most common form of sight-threatening retinopathy in people with diabetes. It affects one in 15 people with diabetes resulting in more than 20 million cases worldwide. Few epidemiological studies have been done to specifically investigate risk factors for diabetic macular oedema, although poor glycaemic and blood pressure control are associated with the presence and development of the disorder. The pathophysiological processes begin with chronic hyperglycaemia, and interplay between vascular endothelial growth factor (VEGF) and inflammatory mediators. Non-invasive imaging using optical coherence tomography has allowed clinicians to detect mild levels of diabetic macular oedema in order to monitor progress and guide treatment. Although focal or grid laser photocoagulation was the traditional mode of treatment, intraocular pharmacotherapy with anti-VEGF agents is now the standard of care. However, these therapies are expensive and resource intensive. Emerging therapeutic strategies include improving efficacy and duration of VEGF suppression, targeting alternative pathways such as inflammation, the kallikrein-kinin system, the angiopoietin-Tie2 system, and neurodegeneration, and using subthreshold and targeted laser therapy. Ongoing research should lead to improvements in screening, diagnosis, and management of diabetic macular oedema.

Impact of early and late age-related macular degeneration on vision-specific functioning

Aim To assess the impact of early and late age-related macular degeneration (AMD) on vision-specific functioning in Singapore Malays. Methods AMD was assessed from fundus photographs. The following endpoints were considered for (a) AMD: no AMD, early AMD, and late AMD; (b) drusen: absence and presence; and (c) retinal pigment epithelium (RPE) abnormality: absence and presence. Vision functioning was assessed using the modified VF-11 scale validated using the Rasch analysis. The overall functioning score was used as the main outcome measure. Results Retinal photographs and vision functioning data were available only for 3252 participants. After age standardisation, the prevalence of early AMD was 3.5% and late AMD 0.34%. In multivariate models, after adjusting for age, gender, education, level of income, smoking status, ocular condition and hypertension, only late AMD was independently associated with poorer vision functioning when compared with no AMD or early AMD (β (β regression coefficient)=−6.4 (CI −11.7 to −2.1; p=0.01)). Early AMD or its principal components, drusen or RPE abnormality, were not independently associated with vision functioning (p>0.05). In adjusted multinomial logistic regression models, people with late AMD were twice as likely (OR=2.23; 95% CI 1.16 to 7.11) to have low overall functioning than those without AMD. Conclusions Late AMD has a significant impact on visual functioning, but early AMD, drusen and RPE changes have no impact. These data highlight the importance of preventive public health strategies targeting patients with early AMD signs in order to prevent progression to late AMD when visual function is compromised.

Defining a Minimum Set of Standardized Patient-centered Outcome Measures for Macular Degeneration

PURPOSE To define a minimum set of outcome measures for tracking, comparing, and improving macular degeneration care. DESIGN Recommendations from a working group of international experts in macular degeneration outcomes registry development and patient advocates, facilitated by the International Consortium for Health Outcomes Measurement (ICHOM). METHODS Modified Delphi technique, supported by structured teleconferences, followed by online surveys to drive consensus decisions. Potential outcomes were identified through literature review of outcomes collected in existing registries and reported in major clinical trials. Outcomes were refined by the working group and selected based on impact on patients, relationship to good clinical care, and feasibility of measurement in routine clinical practice. RESULTS Standardized measurement of the following outcomes is recommended: visual functioning and quality of life (distance visual acuity, mobility and independence, emotional well-being, reading and accessing information); number of treatments; complications of treatment; and disease control. Proposed data collection sources include administrative data, clinical data during routine clinical visits, and patient-reported sources annually. Recording the following clinical characteristics is recommended to enable risk adjustment: age; sex; ethnicity; smoking status; baseline visual acuity in both eyes; type of macular degeneration; presence of geographic atrophy, subretinal fibrosis, or pigment epithelial detachment; previous macular degeneration treatment; ocular comorbidities. CONCLUSIONS The recommended minimum outcomes and pragmatic reporting standards should enable standardized, meaningful assessments and comparisons of macular degeneration treatment outcomes. Adoption could accelerate global improvements in standardized data gathering and reporting of patient-centered outcomes. This can facilitate informed decisions by patients and health care providers, plus allow long-term monitoring of aggregate data, ultimately improving understanding of disease progression and treatment responses.

Prevalence and determinants of undiagnosed diabetic retinopathy and vision-threatening retinopathy in a multiethnic Asian cohort: the Singapore Epidemiology of Eye Diseases (SEED) study

Objective To determine the prevalence and risk factors of undiagnosed diabetic retinopathy (DR), in particular vision-threatening DR (VTDR) in a multiethnic Asian cohort. Design A population-based survey of 3353 Chinese, 3280 Malays and 3400 Indians (73.6% response) aged 40–80 years residing in Singapore. Diabetes mellitus (DM) was defined as random glucose ≥11.1 mmol/L, use of diabetic medication or a previous physician diagnosis. DR severity was graded from retinal photographs following the modified Airlie House classification. VTDR was defined as the presence of severe non-proliferative DR (NPDR), proliferative DR (PDR) or clinically significant macular oedema (CSMO), using the Eye Diseases Prevalence Research Group definition. Participants were deemed ‘undiagnosed’ if they reported no prior physician diagnosis in structured interviews, in those with the condition. Results Of 10 033 participants, 2376 had DM (23.7%), of which 805 (33.9%) had DR. Among 2376 with DM, 11.1% (n=263) were undiagnosed. Among 805 with DR, 671 (83.3%) were undiagnosed. Among 212 with VTDR, 59 (27.3%) were undiagnosed. In multivariate models, factors associated with undiagnosed VTDR were higher low-density lipoprotein (LDL) cholesterol (OR=1.53, 95% CI 0.99 to 2.35, p=0.05) and absence of visual impairment or blindness in any eye in terms of best-corrected vision OR=3.00, 95% CI 1.47 to 6.11, p=0.003). Conclusions In this community, a quarter with VTDR is undiagnosed, and 8 in 10 with any DR are undiagnosed, compared with only 1 in 10 with DM undiagnosed. These findings suggest that screening for diabetes is successful, while screening for DR is currently inadequate in our population. Public health strategies to aid early diagnosis of DR in Singapore are urgently warranted to reduce blindness due to diabetes.

Is aspirin intake associated with early age-related macular degeneration? The Singapore Indian Eye Study

Background/aims To examine the relationship between aspirin intake and early age-related macular degeneration (AMD) among an Asian population. Methods A population based cross sectional study of 3207 ethnic Indians aged 40 years or older residing in Singapore. AMD signs were graded from retinal images following the modified Wisconsin grading system. Information on aspirin intake was obtained from a standardised questionnaire. Results The prevalence of early AMD was 5.6%. Aspirin use was reported by 11.4% of participants. Early AMD signs were present among 10.9% of aspirin users and 4.9% of non-aspirin users (p<0.001). After adjusting for potential confounders, including age, smoking and previous cataract surgery, aspirin use was associated with early AMD (OR 1.50; 95% CI: 1.01 to 2.22). The association weakened and was not significant after additional adjustment for cardiovascular disease (OR 1.38; 95% CI 0.89 to 2.14). In stratified analysis, aspirin use was significantly associated with early AMD in participants with (adjusted OR 2.64, 95% CI 1.31 to 5.36) but not without (OR 0.73; 95% CI 0.36 to 1.51) a history of cardiovascular disease (interaction term, p=0.011). Conclusions Aspirin intake overall was not associated with early AMD in this sample of Asian Indians, but in those with a history of cardiovascular disease the association between aspirin intake and early AMD might warrant further investigation.

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.

THALIA - An automatic hierarchical analysis system to detect drusen lesion images for amd assessment

Age-related macular degeneration (AMD) is a leading cause of permanent blindness. In its early stage AMD is characterized by drusen which are extracellelur deposits in the retina. In this paper, we present THALIA, an automatic system for the detection of drusen images for AMD assessment. First, the macular region of interest is detected using a seeded mode tracking approach. The macular region of interest is then mapped into a new representation using a hierarchicial word transform (HWI). In HWI, dense sampling is first carried out to generate structured pixels which embed local context. These structured pixels are then clustered using hierarchical k-means. The HWI image is subsequently classified using a SVM-based classifier. We have tested THALIA on a dataset of 350 images and obtained an accuracy of 95.46%. Results are promising for further validation of the THALIA system.