Louis Tong

Outdoor Activity and Myopia in Singapore Teenage Children

Aim: To investigate the relationship of outdoor activities and myopia in Singapore teenage children. Methods: Teenage children (1249 participants), examined in the Singapore Cohort study Of Risk factors for Myopia (SCORM), during 2006 were included in analyses. Participants completed questionnaires that quantified total outdoor activity, and underwent an eye examination. Results: The mean total time spent on outdoor activity was 3.24 h/day. The total outdoor activity (h/day) was significantly associated with myopia, odds ratio 0.90 (95% CI 0.84 to 0.96) (p = 0.004), after adjusting for age, gender, ethnicity, school type, books read per week, height, parental myopia, parental education and intelligence quotient. In addition, the total time spent outdoors was associated with significantly less myopic refraction (regression coefficient = 0.17; CI 0.10 to 0.25, p<0.001) and shorter axial length (regression coefficient −0.06 (CI −0.1 to −0.03, p<0.001). Total sports was also significantly negatively associated with myopia (p = 0.008) but not indoor sports (p = 0.16). Conclusions: Participants who spent more time outdoors were less likely to be myopic. Thus, outdoor activity may protect against development of myopia in children, supporting recent Australian data. As near work did not predict outdoor activity, this can be viewed as an independent factor and not merely the reciprocal of near work.

The international workshop on meibomian gland dysfunction: Report of the subcommittee on the epidemiology of, and associated risk factors for, MGD

Scientists have been interested in studying the secretions of the meibomian glands for many years, 1– 8 and diseases associated with the meibomian glands (e.g., cancers, posterior blepharitis) have been noted in the medical literature since at least the early part of the 20th Century. 9 –13 However, the term “meibomian gland dysfunction” (MGD) was only introduced by Korb and Henriquez in 1980. 14 The terminology “meibomian gland disease” was later introduced by Bron et al. 15 as an umbrella term to indicate any disease affecting the meibomian glands (see Definition and Classification). Although the etiology of MGD may differ from that of aqueous-deficient dry eye disease (which is due to insufficient lacrimal gland production), the two conditions share many clinical features, including symptoms of ocular surface irritation and visual fluctuation, altered tear film stability, and potential ocular surface compromise. When MGD is of sufficient degree, it may give rise to the second major subtype of dry eye disease, evaporative dry eye. 16 These subtypes are not mutually exclusive, as has been acknowledged. 16

Identification of Tear Fluid Biomarkers in Dry Eye Syndrome Using iTRAQ Quantitative Proteomics

The proteins found in tears have an important role in the maintenance of the ocular surface and changes in the quality and quantity of tear components reflect changes in the health of the ocular surface. In this study, we have used quantitative proteomics, iTRAQ technology coupled with 2D-nanoLC-nano-ESI-MS/MS and with a statistical model to uncover proteins that are significantly and reliably changed in the tears of dry eye patients in an effort to reveal potential biomarker candidates. Fifty-six patients with dry eye and 40 healthy subjects were recruited for this study. In total, 93 tear proteins were identified with a ProtScore >or=2 (>or=99% confidence). Associated with dry eye were 6 up-regulated proteins, alpha-enolase, alpha-1-acid glycoprotein 1, S100 A8 (calgranulin A), S100 A9 (calgranulin B), S100 A4 and S100 A11 (calgizzarin) and 4 down-regulated proteins, prolactin-inducible protein (PIP), lipocalin-1, lactoferrin and lysozyme. Receiver operating curves (ROC) were evaluated for individual biomarker candidates and a biomarker panel. With the use of a 4-protein biomarker panel, the diagnostic accuracy for dry eye was 96% (sensitivity, 91.0%; specificity, 90.0%). Two biomarker candidates (alpha-enolase and S100 A4) generated from iTRAQ experiments were successfully verified using an ELISA assay. The levels of these 10 tear proteins reflect aqueous secretion deficiency by lacrimal gland, inflammatory status of the ocular surface. The clinical classification of the severity of the dry eye condition was successfully correlated to the proteomics by using three proteins that are associated with inflammation, alpha1-acid glycoprotein 1, S100 A8 and S100 A9. The nine tear protein biomarker candidates (except alpha1-acid glycoprotein 1) were also verified using an independent age-matched patient sample set. This study demonstrated that iTRAQ technology combined with 2D-nanoLC-nanoESI-MS/MS quantitative proteomics is a powerful tool for biomarker discovery.

Atropine for the Treatment of Childhood Myopia: Effect on Myopia Progression after Cessation of Atropine

PURPOSE The aim of this study was to assess the effect on myopia progression after cessation of topical atropine treatment. DESIGN Parallel-group, placebo-controlled, randomized, double-masked study. PARTICIPANTS Four hundred children aged 6 to 12 years with refractive error of spherical equivalent -1.00 to -6.00 diopters (D) and astigmatism of -1.50 D or less. INTERVENTION No intervention was administered. Subjects were followed up for 12 months after stopping treatment, which consisted of either 1% atropine or vehicle eyedrops once nightly for 2 years. Only 1 eye of each subject was chosen through randomization for treatment. MAIN OUTCOME MEASURES The main efficacy outcome measures were change in spherical equivalent refraction as measured by cycloplegic autorefraction and change in ocular axial length as measured by ultrasonography. RESULTS After cessation of atropine drops, the mean progression in the atropine-treated group was -1.14+/-0.80 D over 1 year, whereas the progression in placebo-treated eyes was -0.38+/-0.39 D (P<0.0001). However, after 3 years of participation in the trial (with 2 years on atropine treatment), eyes randomized to atropine have less severe myopia than other eyes. Spherical equivalent was -4.29+/-1.67 D in the atropine-treated eyes compared with -5.22+/-1.38 D in the placebo-treated eyes (P<0.0001). Spherical equivalents in atropine-untreated and placebo-untreated eyes were -5.00+/-1.62 D and -5.28+/-1.43 D, respectively. Over the 3 years, the increase in axial length of the atropine-treated eyes was 0.29+/-0.37 mm compared with 0.52+/-0.45 mm in the placebo-treated eyes (P<0.0001). After cessation of atropine, the amplitude of accommodation and near visual acuity returned to pretreatment levels. CONCLUSIONS After stopping treatment, eyes treated with atropine demonstrated higher rates of myopia progression compared with eyes treated with placebo. However, the absolute myopia progression after 3 years was significantly lower in the atropine group compared with placebo.

Refractive error and monochromatic aberrations in Singaporean children

Higher order optical aberrations were measured in 273 cyclopleged Singaporean school children using a Bausch and Lomb Zywave aberrometer, with 268 of these subjects also undergoing corneal topography measurements (Tomey TMS 2 system). Subjects with low myopia (> -3.00 to -0.50 D) showed slightly, but significantly, less positive levels of spherical aberration than other refractive error groups. Chinese subjects also showed significantly higher amounts of aberrations than Malay subjects, particularly for vertical coma, but also for horizontal coma and spherical aberration. Anterior corneal spherical aberration (calculated from topography) was significantly correlated with whole eye spherical aberration, but did not vary significantly with refractive error or racial background. Residual spherical aberration (i.e. of posterior cornea and crystalline lens) did vary significantly with refractive error and race. Our results do not provide any evidence for aberration-driven form-deprivation as a major mechanism of myopia development.

APPLICATION OF EMPIRICAL MODE DECOMPOSITION (EMD) FOR AUTOMATED DETECTION OF EPILEPSY USING EEG SIGNALS

Epilepsy is a global disease with considerable incidence due to recurrent unprovoked seizures. These seizures can be noninvasively diagnosed using electroencephalogram (EEG), a measure of neuronal electrical activity in brain recorded along scalp. EEG is highly nonlinear, nonstationary and non-Gaussian in nature. Nonlinear adaptive models such as empirical mode decomposition (EMD) provide intuitive understanding of information present in these signals. In this study a novel methodology is proposed to automatically classify EEG of normal, inter-ictal and ictal subjects using EMD decomposition. EEG decomposition using EMD yields few intrinsic mode functions (IMF), which are amplitude and frequency modulated (AM and FM) waves. Hilbert transform of these IMF provides AM and FM frequencies. Features such as spectral peaks, spectral entropy and spectral energy in each IMF are extracted and fed to decision tree classifier for automated diagnosis. In this work, we have compared the performance of classification using two types of decision trees (i) classification and regression tree (CART) and (ii) C4.5. We have obtained the highest average accuracy of 95.33%, average sensitivity of 98%, and average specificity of 97% using C4.5 decision tree classifier. The developed methodology is ready for clinical validation on large databases and can be deployed for mass screening.

Phospholipase D in the human ocular surface and in pterygium.

Background:Post-exposure prophylaxis (PEP) is currently recommended after certain high-risk exposures, and pre-exposure prophylaxis (PrEP) is undergoing evaluation in clinical trials. Media reports have suggested substantial levels of community PrEP use despite its unproven effectiveness. Methods:We conducted a cross-sectional survey of 1819 HIV-uninfected gay/bisexual men in California to assess PEP and PrEP awareness and use. Results:Overall, 47% reported PEP awareness and 4% ever used PEP. Men who were older than 25 years of age (odds ratio [OR] = 2.2, 95% confidence interval [CI]: 1.5 to 3.1), were white (OR = 2.2, 95% CI: 1.6 to 3.0), had an annual income >

Extensive characterization of human tear fluid collected using different techniques unravels the presence of novel lipid amphiphiles

100,000 (OR = 2.0, 95% CI: 1.2 to 3.4), self-identified as gay/homosexual (OR = 2.4, 95% CI: 1.4 to 4.3), and had unprotected anal sex (OR = 1.8, 95% CI: 1.3 to 2.3) or sex under the influence of a drug (OR = 2.0, 95% CI: 1.5 to 2.7) were more likely to be aware of PEP, whereas speed users (OR = 0.6, 95% CI: 0.4 to 0.9) were less likely to be aware of PEP. Only 16% reported PrEP awareness, and <1% ever used PrEP. Unprotected anal sex (OR = 1.6, 95% CI: 1.1 to 2.3) and sex under the influence of a drug (OR = 1.5, 95% CI: 1.0 to 2.2) were associated with PrEP awareness. Conclusions:PEP awareness and use were modest and PrEP use was rare among gay/bisexual men in California. Although PrEP is not currently recommended, community education on the availability of PEP is suggested.PURPOSE Pterygium is a fibro-vascular disease of unknown etiology characterized by proliferation and advancement of tissue onto the cornea. Phospholipase Ds (PLDs) are members of an important class of enzymes involved in inflammation and differentiation. In cultured corneal epithelial cells, these enzymes play a role in wound healing, and in other contexts, they suppress apoptosis and increase cell motility. We aimed to study the presence of PLD subtypes in native ocular surface tissue and pterygium. METHODS This study involved paired control or uninvolved conjunctival and pterygium tissues from 6 patients. Reverse transcription semiquantitative and quantitative polymerase chain reactions were performed to assess transcript levels for PLD1-5 in normal conjunctiva and pterygium tissue. Immunofluorescent staining by using antibodies against PLD1/2 was used to study the expression and tissue distribution. Western blots were performed for protein detection and to confirm the specificity of the antibodies used. RESULTS PLD1, 2, 3, and 4 transcripts were detected in normal conjunctiva tissue, and types 2, 3, and 4 were upregulated in pterygium. Immunofluorescent staining showed the presence of phospholipase-D1/2 in normal cornea, conjunctival, and pterygial epithelia. In normal cornea and conjunctival epithelia, the expression was mainly localized to the nuclei of the basal and suprabasal epithelial cells, whereas in pterygium, this expression was limited to the cytoplasm and peri-plasma membrane regions. Western blot confirmed the presence of PLD1/2 in proteins extracted from pterygium and conjunctiva tissue. CONCLUSIONS PLD subtypes are present in human ocular surface epithelium. PLD may be involved in pterygium pathogenesis.

Meibum Lipid Composition in Asians with Dry Eye Disease

The tear film covers the anterior eye and the precise balance of its various constituting components is critical for maintaining ocular health. The composition of the tear film amphiphilic lipid sublayer, in particular, has largely remained a matter of contention due to the limiting concentrations of these lipid amphiphiles in tears that render their detection and accurate quantitation tedious. Using systematic and sensitive lipidomic approaches, we validated different tear collection techniques and report the most comprehensive human tear lipidome to date; comprising more than 600 lipid species from 17 major lipid classes. Our study confers novel insights to the compositional details of the existent tear film model, in particular the disputable amphiphilic lipid sublayer constituents, by demonstrating the presence of cholesteryl sulfate, O-acyl-ω-hydroxyfatty acids, and various sphingolipids and phospholipids in tears. The discovery and quantitation of the relative abundance of various tear lipid amphiphiles reported herein are expected to have a profound impact on the current understanding of the existent human tear film model.

Cornea biomechanical characteristics and their correlates with refractive error in Singaporean children.

Background Previous lipidomic analyses of the human meibum had largely focused on individuals from non-Asian populations, despite the higher prevalence of dysfunctional tear syndrome (DTS) observed across Asia. Information pertaining to the alterations in lipid profiles in relation to DTS onset and progression is also lacking and warrants comprehensive experimental analysis. Methodologies/Principal Findings We examined the meibum lipidome of 27 DTS patients and 10 control subjects for a total of 256 lipid species from 12 major lipid classes, including cholesteryl ester (CE), wax ester (WE), triacylglyceride (TAG), (O-acyl)-ω-hydroxy fatty acid (OAHFA), glycerophospholipids (phosphatidylcholine, PC; phosphatidylethanolamine, PE; phosphatidylinositol, PI; phosphatidylglycerol, PG) and sphingolipids (sphingomyelin, SM; ceramide, Cer; glucosylceramide, GluCer; dihexosylceramide, DihexCer). Neutral lipids were analysed using high-performance liquid-chromatography coupled with mass spectrometry (HPLC/MS) and tandem mass spectrometry (MS/MS) was used for the qualitative and quantitative analysis of polar lipid species. DTS patients were classified into three severity groups (i.e. mild, moderate and severe) based on the ocular surface disease index (OSDI). A significantly lower level of TAG (p<0.05) was observed in patients under the moderate category compared to the mild category. Notably, a number of OAHFA species displayed consistently decreasing levels that correlate with increasing disease severity. An attempt was also made to investigate the changes in meibum lipid profiles of DTS patients compared to normal individuals classified based on OSDI score. Several unsaturated TAG and PC species were found at significantly higher levels (p<0.05) in patients than controls. Conclusion The current study presents, for the first time, a comprehensive lipidome of meibum from individuals of an Asian ethnicity, which can potentially offer new insights into the higher prevalence of DTS observed amongst Asian populations. This study also represents an attempt towards identification of lipid species in meibum which could serve as marker for DTS.