Singapore Eye Research Institute

Singapore, Singapore

Singapore Eye Research Institute

Singapore, Singapore
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Wang X.,Singapore Eye Research Institute
Journal of Glaucoma | Year: 2017

PURPOSE:: To assess the accuracy of crowdsourcing for grading optic nerve images for glaucoma using Amazon Mechanical Turk before and after training modules. MATERIALS AND METHODS:: Images (n=60) from 2 large population studies were graded for glaucoma status and vertical cup-to-disc ratio (VCDR). In the baseline trial, users on Amazon Mechanical Turk (Turkers) graded fundus photos for glaucoma and VCDR after reviewing annotated example images. In 2 additional trials, Turkers viewed a 26-slide PowerPoint training or a 10-minute video training and passed a quiz before being permitted to grade the same 60 images. Each image was graded by 10 unique Turkers in all trials. The mode of Turker grades for each image was compared with an adjudicated expert grade to determine accuracy as well as the sensitivity and specificity of Turker grading. RESULTS:: In the baseline study, 50% of the images were graded correctly for glaucoma status and the area under the receiver operating characteristic (AUROC) was 0.75 [95% confidence interval (CI), 0.64-0.87]. Post-PowerPoint training, 66.7% of the images were graded correctly with AUROC of 0.86 (95% CI, 0.78-0.95). Finally, Turker grading accuracy was 63.3% with AUROC of 0.89 (95% CI, 0.83-0.96) after video training. Overall, Turker VCDR grades for each image correlated with expert VCDR grades (Bland-Altman plot mean difference=−0.02). CONCLUSIONS:: Turkers graded 60 fundus images quickly and at low cost, with grading accuracy, sensitivity, and specificity, all improving with brief training. With effective education, crowdsourcing may be an efficient tool to aid in the identification of glaucomatous changes in retinal images. Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.


PURPOSE:: To investigate the influence of choroidal vascular hyperpermeability (CVH) and choroidal thickness on treatment outcomes in eyes with polypoidal choroidal vasculopathy (PCV) undergoing anti–vascular endothelial growth factor monotherapy or combination therapy of photodynamic therapy and anti–vascular endothelial growth factor injections. METHODS:: The authors performed a prospective, observational cohort study involving 72 eyes of 72 patients with polypoidal choroidal vasculopathy (mean age 68.6 years, 51% men) treated with either monotherapy (n = 41) or combination therapy (n = 31). Each eye was imaged with color fundus photography, fluorescent angiography, indocyanine green angiography, and spectral domain optical coherence tomography. Indocyanine green angiography images were used to evaluate CVH, and spectral domain optical coherence tomography was used to measure central choroidal thickness. Changes in visual acuity over 12 months, and number of anti–vascular endothelial growth factor injections were investigated. RESULTS:: Choroidal vascular hyperpermeability was present in 31 eyes (43.1%). Visual acuity change over 12 months was numerically better in the CVH group compared with the CVH (−) group (−0.099 and −0.366 logarithm of the minimal angle of resolution unit in the CVH (−) and CVH (+) groups, respectively, multivariate P = 0.063) and significantly better in a matched pair analysis (P = 0.033). Furthermore, in the combination therapy group, the number of injection was significantly lower in the CVH (+) group compared with the CVH (−) group (4.68 vs. 2.58 injections/year in the CVH (−) and CVH (+) groups; P = 0.0044). There was no significant relationship between treatment response and choroidal thickening. CONCLUSION:: The presence of CVH is associated with better visual outcome in eyes with polypoidal choroidal vasculopathy and lower injection number in combination therapy. Thus, CVH, but not choroidal thickness, should be further evaluated as a potential biomarker for selecting patients for combination therapy. © 2017 by Ophthalmic Communications Society, Inc.


PURPOSE:: To characterize and compare morphologic and vascular features of the choroid in patients with typical age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV) and to determine if PCV subtypes can be identified based on these choroidal features. METHODS:: Choroidal features of patients with AMD and PCV recruited from the prospectively planned Asian AMD Phenotyping Study were analyzed. Patients underwent choroidal imaging using spectral-domain optical coherence tomography with enhanced depth imaging. Raw optical coherence tomographic images were loaded on a custom-written application on MATLAB that enabled delineation for detailed morphologic and vascular analyses, including the curvature of the choroid–sclera interface, number of inflection points, choroidal thickness and choroidal vascular area within the macular (6 mm centered on fovea) and foveal (1.5 mm centered on fovea) regions. An inflection point represents the contour of the choroid–sclera interface, with >1 point signaling irregular shape. RESULTS:: A total of 156 eyes of 156 patients (78 affected eyes of 78 patients with typical AMD and 78 affected eyes of 78 patients with PCV) were analyzed. Eyes with PCV had thicker baseline choroidal thickness and greater choroidal vascular area compared with those with typical AMD (P < 0.05); these differences were no longer significant after adjusting for age and hypertension (P > 0.05). Typical PCV subtype with choroidal thickness of ≥257 μm had significantly greater choroidal vascular area at macular (mean difference = 0.054 mm; P < 0.001) and foveal (mean difference = 0.199 mm; P < 0.001) regions compared with eyes with typical AMD. However, eyes with PCV without thick choroid had similar choroidal vascular area as eyes with typical AMD. CONCLUSION:: Based on the choroidal vascular features, two subtypes of PCV can be classified: typical PCV with increased choroid vascularity and polypoidal choroidal neovascularization with low choroidal vascularity. These data provide further understanding of different AMD and PCV subtypes. © 2017 by Ophthalmic Communications Society, Inc.


Strouthidis N.G.,University College London | Strouthidis N.G.,Singapore Eye Research Institute | Girard M.J.A.,National University of Singapore
Current Opinion in Pharmacology | Year: 2013

Over the past decade, engineering principles have been used to explain why a mechanical load, intraocular pressure, can lead to the development of glaucomatous optic neuropathy. This has led to the 'biomechanical theory' of glaucoma, which posits that the behavior of optic nerve head connective tissues (specifically within the peripapillary sclera and lamina cribrosa) in response to intraocular pressure (regardless of its magnitude) can directly and indirectly influence the physiology and pathophysiology of the optic nerve head. Given that the biomechanics of the sclera and lamina cribrosa probably influence retinal ganglion cell loss in glaucoma, the idea that altering biomechanical behavior might be protective against glaucoma is an appealing notion. There is some evidence to suggest that stiffening the peripapillary sclera may be protective against the development of glaucoma in an animal model. It is technically possible to stiffen the sclera in vivo using collagen cross-linking techniques already applied in vivo to the cornea in the treatment of keratoconus. It has yet to be established whether scleral cross-linking is safe in humans and that it confers anything more than a theoretical advantage in terms of reducing the risk of glaucomatous damage. © 2012 Elsevier Ltd.


Morgan I.G.,Australian National University | Morgan I.G.,Sun Yat Sen University | Ohno-Matsui K.,Tokyo Medical and Dental University | Saw S.-M.,National University of Singapore | Saw S.-M.,Singapore Eye Research Institute
The Lancet | Year: 2012

Myopia has emerged as a major health issue in east Asia, because of its increasingly high prevalence in the past few decades (now 80-90% in school-leavers), and because of the sight-threatening pathologies associated with high myopia, which now affects 10-20% of those completing secondary schooling in this part of the world. Similar, but less marked, changes are occurring in other parts of the world. The higher prevalence of myopia in east Asian cities seems to be associated with increasing educational pressures, combined with life-style changes, which have reduced the time children spend outside. There are no reported major genes for school myopia, although there are several genes associated with high myopia. Any genetic contribution to ethnic differences may be small. However, to what extent many genes of small effect and gene-environment interactions contribute to variations in school myopia within populations remains to be established. There are promising optical and pharmacological interventions for preventing the development of myopia or slowing its progression, which require further validation, and promising vision-sparing treatments for pathological myopia.


Li Z.,Institute of Materials Research and Engineering of Singapore | Loh X.J.,Institute of Materials Research and Engineering of Singapore | Loh X.J.,National University of Singapore | Loh X.J.,Singapore Eye Research Institute
Chemical Society Reviews | Year: 2015

Polyhydroxyalkanoates (PHAs) are excellent candidate biomaterials due to their exceptional biodegradability and biocompatibility. However, PHAs need to have tunable hydrophilicity, chemical functionalities, and appropriate hydrolytic stability to expand their therapeutic applications towards more advanced areas. In this Tutorial Review, we present the most recent progress in the synthetic strategies of PHA-based water soluble polymers, including the functionalisation of PHAs with polar functional groups and the block/graft copolymerization of PHAs with hydrophilic components in various polymeric architectures. These chemically modified water soluble PHAs have significant impact on materials engineering and show great value in the fulfilment of smart biomaterials in emerging areas. The applications of water soluble PHAs in controlled drug release, cancer therapy, DNA/siRNA delivery and tissue engineering in new aspects are discussed. In addition, water soluble PHA monomer production will be briefly introduced, with emphasis on its bio-significance in medical physiology and the therapeutic effect in the treatment of diseases. This journal is © The Royal Society of Chemistry.


Mitchell P.,University of Sydney | Wong T.Y.,Singapore Eye Research Institute
American Journal of Ophthalmology | Year: 2014

Purpose To provide evidence-based recommendations for diabetic macular edema (DME) management based on updated information from publications on DME treatment modalities. Design Perspective. Methods A literature search for "diabetic macular edema" or "diabetic maculopathy" was performed using the PubMed, Cochrane Library, and ClinicalTrials.gov databases to identify studies from January 1, 1985 to July 31, 2013. Meta-analyses, systematic reviews, and randomized controlled trials with at least 1 year of follow-up published in the past 5 years were preferred sources. Results Although laser photocoagulation has been the standard treatment for DME for nearly 3 decades, there is increasing evidence that superior outcomes can be achieved with anti-vascular endothelial growth factor (anti-VEGF) therapy. Data providing the most robust evidence from large phase II and phase III clinical trials for ranibizumab demonstrated visual improvement and favorable safety profile for up to 3 years. Average best-corrected visual acuity change from baseline ranged from 6.1-10.6 Early Treatment Diabetic Retinopathy Study (ETDRS) letters for ranibizumab, compared to 1.4-5.9 ETDRS letters with laser. The proportion of patients gaining ≥10 or ≥15 letters with ranibizumab was at least 2 times higher than that of patients treated with laser. Patients were also more likely to experience visual loss with laser than with ranibizumab treatment. Ranibizumab was generally well tolerated in all studies. Studies for bevacizumab, aflibercept, and pegaptanib in DME were limited but also in favor of anti-VEGF therapy over laser. Conclusions Anti-VEGF therapy is superior to laser photocoagulation for treatment of moderate to severe visual impairment caused by DME.


Baskaran M.,Singapore Eye Research Institute
Investigative ophthalmology & visual science | Year: 2012

To evaluate the diagnostic performance of classification algorithms based on Linear Discriminant Analysis (LDA) and Classification And Regression Tree (CART) methods, compared with optic nerve head (ONH) and retinal nerve fiber layer (RNFL) parameters measured by high-definition optical coherence tomography (Cirrus HD-OCT) for discriminating glaucoma subjects. Consecutive glaucoma subjects (Training data = 184; Validation data = 102) were recruited from an eye center and normal subjects (n = 508) from an ongoing Singaporean Chinese population-based study. ONH and RNFL parameters were measured using a 200 × 200 scan protocol. LDA and CART were computed and areas under the receiver operating characteristic curve (AUC) compared. Average RNFL thickness (AUC 0.92, 95% confidence interval [CI] 0.91, 0.93), inferior RNFL thickness (AUC 0.92, 95% CI 0.91, 0.93), vertical cup-disc ratio (AUC 0.91, 95% CI 0.90, 0.92) and rim area/disc area ratio (AUC 0.90, 95% CI 0.86, 0.93) discriminated glaucoma better than other parameters (P ≤ 0.033). LDA (AUC 0.96, 95% CI 0.95, 0.96) and CART (0.98, 95% CI 0.98, 0.99) outperformed all parameters for diagnostic accuracy (P ≤ 0.005). Misclassification rates in LDA (8%) and CART (5.6%) were found to be low. The AUC of LDA for the validation data was 0.98 (0.95, 0.99) and CART was 0.99 (0.99, 0.994). CART discriminated mild glaucoma from normal better than LDA (AUC 0.94 vs. 0.99, P < 0.0001). Classification algorithms based on LDA and CART can be used in HD-OCT analysis for glaucoma discrimination. The CART method was found to be superior to individual ONH and RNFL parameters for early glaucoma discrimination.


Chee S.-P.,Singapore Eye Research Institute
Journal of Cataract and Refractive Surgery | Year: 2012

A technique that uses an implanted intraocular lens (IOL) to create a barrier for the management of posterior capsule rupture is described. When a rupture occurs, surgery is halted and a dispersive ophthalmic viscosurgical device (OVD) injected into the anterior chamber to prevent vitreous prolapse. The remaining nucleus is maneuvered into the anterior chamber away from the pupillary space. The posterior capsule tear is converted into a continuous curvilinear capsulorhexis where possible. Dissociated anterior vitrectomy is performed as indicated, keeping the large nuclear fragments trapped in the OVD-filled anterior chamber. An IOL is implanted in the capsular bag or sulcus with optic capture through the anterior capsulorhexis. Using reduced parameters, phacoemulsification of the remaining fragments is completed over the IOL, which functions as a barrier to seal off the vitreous cavity. Residual nuclear fragments and vitreous are cleared from beneath the optic by placing the vitreous cutter under the optic, recapturing the optic before the instruments are removed from the eye. Financial Disclosure: The author has no financial or proprietary interest in any material or method mentioned. © 2012 ASCRS and ESCRS.


Li X.,Singapore Eye Research Institute
Investigative ophthalmology & visual science | Year: 2013

To investigate potential racial/ethnic differences in retinal vascular geometric parameters in a multiethnic Asian population (Chinese, Malay, and Indian) free of clinical diseases. A series of retinal vascular parameters were measured from retinal photographs using a computer-assisted program following a standardized protocol. Healthy participants were defined as nonsmokers, the absence of diabetes mellitus, uncontrolled hypertension, obesity, stroke, heart disease, glaucoma, and retinopathy. THERE WERE SIGNIFICANT DIFFERENCES IN MEASUREMENTS OF RETINAL VASCULAR CALIBER, TORTUOSITY, AND FRACTAL DIMENSION AMONG THE THREE ETHNIC GROUPS. IN MULTIPLE LINEAR REGRESSION MODEL CONTROLLING FOR AGE, SEX, BODY MASS INDEX, SYSTOLIC BLOOD PRESSURE, CHOLESTEROL, AND GLUCOSE LEVELS, INDIANS HAD THE LARGEST ARTERIOLAR AND VENULAR CALIBERS (ARTERIOLES [SE]: 158.94 μm [1.00]; venules: 228.26 μm [1.53]), followed by Malays (arterioles: 138.31 μm [0.74]; venules: 204.26 μm [1.13]), and then Chinese (arterioles: 131.20 μm [0.84]; venules: 195.09 μm [1.28]). Chinese had the largest arteriolar and venular tortuosity (arterioles [× $${10}^{5}$$]: 7.20 [0.08] VENULES [ $${10}^{5}$$]: 9.09 [0.10]), and venular fractal dimension (1.244 [0.003]). There were no statistically significant differences in other retinal vascular parameters after correcting multiple comparisons by the method of modified false discovery rate. We found that among ethnic groups composed of healthy Chinese, Malay, and Indians, there were statistically significant differences in several retinal parameters. There exist racial influences in retinal vascular parameters and other yet unknown or unmeasured environmental factor or lifestyle habits and genetic variations not related to race that may also contribute to these differences.

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