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Fuest M.,Singapore Eye Research Institute
Eye and Contact Lens | Year: 2017

ABSTRACT:: Corneal hydrops affects approximately 2.5% of keratoconus (KC) cases, predominantly young males approximately 25 years of age with steep cones. Often, patients are left with a vision-reducing corneal scar frequently necessitating surgical treatment. Penetrating keratoplasty (PK) has worse survival outcomes in hydrops than in general KC cases. Deep anterior lamellar keratoplasty (DALK) is a nonpenetrating technique believed to achieve equal or better outcomes in visual acuity, graft survival, endothelial rejection rates, and endothelial cell survival in comparison with PK, while maintaining globe integrity and the patientsʼ Descemet membrane (DM) and endothelium. Outcomes for patients with KC are promising. After hydrops, a corneal scar involving DM complicates the ability to perform DALK using standard techniques. So far few case series described successful treatment of hydrops scars with DALK. In this review, we summarize, evaluate, and discuss the current known approaches to DALK in patients after hydrops. © 2017 Contact Lens Association of Ophthalmologists, Inc.

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.

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 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.

Chee S.-P.,Singapore Eye Research Institute
Journal of Ocular Pharmacology and Therapeutics | Year: 2012

Purpose: To assess the safety and feasibility of a moxifloxacin-loaded punctum plug (MP) in 2 groups of cataract patients. Methods: Two prospective, single-arm, Phase I studies were conducted with 20 cataract patients (10 per study) at the Singapore National Eye Center. After cataract surgery, the MP was inserted into the punctum, and follow-up assessments were conducted at 1h, 24h, and on days 3, 7, 10, 20, and 30. Study endpoints included MP retention, ease of placement, and moxifloxacin concentrations in the tear fluid. Moxifloxacin concentrations were targeted to be ≥250ng/mL through 7 days, with detectable levels through day 10. After the course of therapy, the plug would resorb and be absent from the punctum by day 30. Slit lamp evaluations were performed, and intraocular pressure measurements were performed on days 1, 3, 7, 10, 20, and 30. Patients were queried for the presence or absence of several ocular sensations in the operative eye. Due to the variability in tear film antibiotic concentrations observed in the first study, a second study was conducted with more stringent concomitant drop administration and tear sample collection criteria. Results: MP retention in the punctum was 95% (19/20) through day 10, and all plugs were absent at day 30. Average moxifloxacin concentrations in the tear film ranged from 155 to 785ng/mL for Study 1 and 2,465 to 3,236ng/mL for Study 2 through day 7. These values were above the target of 250ng/mL for all time points except for day 1 of Study 1. For both studies, moxifloxacin concentrations in the tear film were above detectable levels at day 10. The plugs were well tolerated, and there were no adverse events as defined by the protocol, and no ocular complaints or findings other than normal post-cataract symptoms. Conclusions: The MP delivered and maintained moxifloxacin tear fluid concentrations at therapeutic levels above the MIC90 values for common susceptible conjunctivitis pathogens for 7 days (Study 2). The MP also exhibited a favorable safety and tolerability profile and, hence, may be a viable alternative to topical antibiotic drops for the treatment of bacterial conjunctivitis. © Copyright 2012, Mary Ann Liebert, Inc.

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.

Tan X.W.,Singapore Eye Research Institute
Journal of biomedical materials research. Part B, Applied biomaterials | Year: 2012

Functionalization of material surfaces can improve their biointegration and bactericidal effect. To expand the biomedical applications of titanium in artificial cornea implantation surgery, titanium alloy substrates were coated with polydopamine and dual bound with recombinant vascular endothelial growth factor (VEGF) and anti-microbial peptide (AMP), SESB2V. Successful chemical binding was assessed with attenuated total reflectance-Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy. Coating thickness was assessed by atomic force microscopy. Cellular studies revealed that the functionalized substrates displayed the abilities to enhance primary human corneal fibroblast adhesion, proliferation, and viability. Angiogenesis assay with human mesenchymal stem cells was used to verify the biological functions of immobilized VEGF while bactericidal assay was evaluated for the anti-microbial activities of immobilized SESB2V peptide. We found that the titanium surface that was sequentially functionalized with VEGF and SESB2V had enhanced fibroblast proliferation and anti-microbial properties. The incorporation of such peptides into an artificial cornea implant is important for implant-tissue integration and wound healing. This may improve implant integration and reduce the risk of device infection following artificial cornea implantation. Copyright © 2012 Wiley Periodicals, Inc.

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