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Glaucoma: HELP
Articles by Tin Aung
Based on 249 articles published since 2008
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Between 2008 and 2019, T. Aung wrote the following 249 articles about Glaucoma.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4 · 5 · 6 · 7 · 8 · 9 · 10
1 Editorial Mechanisms underlying acute angle closure. 2017

Nongpiur, Monisha E / Aung, Tin. ·Singapore Eye Research Institute, Singapore National Eye Centre, Singapore. · Duke-NUS Medical School, Singapore. · Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. ·Clin Exp Ophthalmol · Pubmed #28618456.

ABSTRACT: -- No abstract --

2 Editorial Flavonoids and glaucoma: revisiting therapies from the past. 2015

Milea, Dan / Aung, Tin. ·Singapore Eye Research Institute, Singapore National Eye Centre, 11 Third Hospital Avenue, Singapore, 168751, Singapore. · Neuroscience and Behavioural Disorders Group, Duke-NUS, Singapore, Singapore. · Singapore Eye Research Institute, Singapore National Eye Centre, 11 Third Hospital Avenue, Singapore, 168751, Singapore. aung.tin@snec.com.sg. · Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. aung.tin@snec.com.sg. ·Graefes Arch Clin Exp Ophthalmol · Pubmed #26344732.

ABSTRACT: -- No abstract --

3 Editorial Can we screen for angle closure? 2011

Sakata, Lisandro M / Aung, Tin. · ·Am J Ophthalmol · Pubmed #21420519.

ABSTRACT: -- No abstract --

4 Review Role of anterior segment optical coherence tomography in angle-closure disease: a review. 2018

Porporato, Natalia / Baskaran, Mani / Aung, Tin. ·Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore. · Duke-NUS Graduate Medical School, Singapore, Singapore. · Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. ·Clin Exp Ophthalmol · Pubmed #29193702.

ABSTRACT: This article aims to review the published literature pertaining to the use of anterior segment optical coherence tomography (AS-OCT) in the evaluation of angle-closure disease. Searches on the available published literature were last conducted on 15 June 2017. Rated as Level I evidence, we found that AS-OCT has shown good sensitivity and moderate diagnostic accuracy to detect narrow angles when compared with gonioscopy. AS-OCT quantitative and qualitative parameters demonstrated strong association with the presence of gonioscopically closed angles. This technology provides an objective non-contact method of assessing the angle that is well tolerated by the patient and correlates well with the information provided by gonioscopy.

5 Review Glaucoma. 2017

Jonas, Jost B / Aung, Tin / Bourne, Rupert R / Bron, Alain M / Ritch, Robert / Panda-Jonas, Songhomitra. ·Department of Ophthalmology, Medical Faculty Mannheim of the Ruprecht-Karls-University of Heidelberg, Heidelberg, Germany. Electronic address: jost.jonas@medma.uni-heidelberg.de. · Singapore Eye Research Institute, Singapore; Singapore National Eye Centre, Singapore; Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. · Vision and Eye Research Unit, Anglia Ruskin University, Cambridge, UK. · Department of Ophthalmology, University Hospital, Dijon, France; Eye and Nutrition Research Group, Bourgogne Franche-Comté University, Dijon, France. · Einhorn Clinical Research Center, New York Eye and Ear Infirmary of Mount Sinai, New York, NY, USA. · Department of Ophthalmology, Medical Faculty Mannheim of the Ruprecht-Karls-University of Heidelberg, Heidelberg, Germany. ·Lancet · Pubmed #28577860.

ABSTRACT: Glaucoma is a heterogeneous group of diseases characterised by cupping of the optic nerve head and visual-field damage. It is the most frequent cause of irreversible blindness worldwide. Progression usually stops if the intraocular pressure is lowered by 30-50% from baseline. Its worldwide age-standardised prevalence in the population aged 40 years or older is about 3·5%. Chronic forms of glaucoma are painless and symptomatic visual-field defects occur late. Early detection by ophthalmological examination is mandatory. Risk factors for primary open-angle glaucoma-the most common form of glaucoma-include older age, elevated intraocular pressure, sub-Saharan African ethnic origin, positive family history, and high myopia. Older age, hyperopia, and east Asian ethnic origin are the main risk factors for primary angle-closure glaucoma. Glaucoma is diagnosed using ophthalmoscopy, tonometry, and perimetry. Treatment to lower intraocular pressure is based on topical drugs, laser therapy, and surgical intervention if other therapeutic modalities fail to prevent progression.

6 Review Why does acute primary angle closure happen? Potential risk factors for acute primary angle closure. 2017

Zhang, Xiulan / Liu, Yaoming / Wang, Wei / Chen, Shida / Li, Fei / Huang, Wenbin / Aung, Tin / Wang, Ningli. ·Zhongshan Ophthalmic Center, State Key Laboratory of Ophthalmology, Sun Yat-Sen University, Guangzhou, China. Electronic address: zhangxl2@mail.sysu.edu.cn. · Zhongshan Ophthalmic Center, State Key Laboratory of Ophthalmology, Sun Yat-Sen University, Guangzhou, China. · Singapore Eye Research Institute and Singapore National Eye Centre, Singapore; Department of Ophthalmology, National University of Singapore, Singapore. · Department of Ophthalmology, Beijing Tongren Hospital, Capital Medical University, Beijing, China. ·Surv Ophthalmol · Pubmed #28428109.

ABSTRACT: Acute primary angle closure is an ocular emergency and requires immediate management to avoid blindness. Narrow anterior chamber angle, advanced age, female gender, and Asian ethnic background are considered risk factors for acute primary angle closure. The predictive power of these factors is, however, relatively poor, and many questions remain unanswered because acute primary angle closure eventually develops in only a relatively small proportion of anatomically predisposed eyes. We summarize the potential roles of various factors in the pathogenesis of acute primary angle closure.

7 Review Glaucoma Genetics: Recent Advances and Future Directions. 2016

Aung, Tin / Khor, Chiea Chuen. ·From the *Singapore Eye Research Institute, Singapore National Eye Centre; †Yong Loo Lin School of Medicine, National University of Singapore; and ‡Genome Institute of Singapore, Singapore. ·Asia Pac J Ophthalmol (Phila) · Pubmed #27488067.

ABSTRACT: Once considered primarily a disease of aging caused by unknown environmental influences, the notion that heritable factors could significantly contribute to the pathogenesis of sporadic glaucoma has rapidly gained traction. In part, this is due to the rapid and definitive identification of genes with strong effects on familial, earlier onset forms of glaucoma. Although the endpoint of glaucoma is irreversible optic nerve damage accompanied by blindness, the initial inciting trigger could differ. To this end, well-powered genome-wide association studies have each been conducted for primary open-angle glaucoma, primary angle-closure glaucoma, along with exfoliation syndrome and glaucoma. Each of these studies has revealed sets of significantly associated genetic loci implicating biological pathways that do not overlap between the forms of glaucoma. Although substantial biological insight has been gained from their identification, much further work remains to definitively link the implicated genetic variants with glaucoma causation. It is also hoped that the genetic findings could point us to potential routes of therapy beyond that of intraocular pressure-lowering medications or surgery.

8 Review Glaucoma in Asia: regional prevalence variations and future projections. 2016

Chan, Errol Wei'en / Li, Xiang / Tham, Yih-Chung / Liao, Jiemin / Wong, Tien Yin / Aung, Tin / Cheng, Ching-Yu. ·Department of Ophthalmology, National University of Singapore and National University Health System, Singapore, Singapore. · Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, USA Duke-NUS Graduate Medical School, Singapore, Singapore. · Department of Ophthalmology, National University of Singapore and National University Health System, Singapore, Singapore Singapore Eye Research Institute, Singapore, Singapore. · Department of Ophthalmology, National University of Singapore and National University Health System, Singapore, Singapore Duke-NUS Graduate Medical School, Singapore, Singapore Singapore Eye Research Institute, Singapore, Singapore. ·Br J Ophthalmol · Pubmed #26112871.

ABSTRACT: PURPOSE: To evaluate glaucoma prevalence and disease burden across Asian subregions from 2013 to 2040. METHODS: We conducted a systematic review and meta-analysis of 23 population-based studies of 1318 primary open angle glaucoma (POAG) cases in 66,800 individuals and 691 primary angle closure glaucoma (PACG) cases in 72,767 individuals in Asia. Regions in Asia were defined based on United Nations' (UN) classification of macro-geographic regions. PubMed, Medline and Web of Science databases were searched for population-based glaucoma prevalence studies using standardised criteria published to 31 December 2013. Pooled glaucoma prevalence for individuals aged 40-80 years was calculated using hierarchical Bayesian approaches. Prevalence differences by geographic subregion, subtype and habitation were examined with random effects meta-regression models. Estimates of individuals with glaucoma from 2013 to 2040 were based on the UN World Population Prospects. RESULTS: In 2013, pooled overall glaucoma prevalence was 3.54% (95% credible interval (CrI) 1.83 to 6.28). POAG (2.34%, 95% CrI 0.96 to 4.55) predominated over PACG (0.73%, 95% CrI 0.18 to 1.96). With age and gender adjustment, PACG prevalence was higher in East than South East Asia (OR 5.55, 95% CrI 1.52 to 14.73), and POAG prevalence was higher in urban than rural populations (OR 2.11, 95% CrI 1.57 to 2.38). From 2013 to 2040, South Central Asia will record the steepest increase in number of glaucoma individuals from 17.06 million to 32.90 million compared with other Asian subregions. In 2040, South-Central Asia is also projected to overtake East Asia for highest overall glaucoma and POAG burden, while PACG burden remains highest in East Asia. CONCLUSIONS: Across the Asian subregions, there was greater glaucoma burden in South-Central and East Asia. Sustainable public health strategies to combat glaucoma in Asia are needed.

9 Review Choroidal physiology and primary angle closure disease. 2015

Zhang, Xiulan / Wang, Wei / Aung, Tin / Jonas, Jost B / Wang, Ningli. ·Zhongshan Ophthalmic Center, State Key Laboratory of Ophthalmology, Sun Yat-Sen University, Guangzhou, China. Electronic address: zhangxl2@mail.sysu.edu.cn. · Zhongshan Ophthalmic Center, State Key Laboratory of Ophthalmology, Sun Yat-Sen University, Guangzhou, China. · Glaucoma Service, Singapore National Eye Centre, Singapore. · Department of Ophthalmology, Medical Faculty Mannheim of the Ruprecht-Karls-University of Heidelberg, Seegartenklinik, Heidelberg, Germany. · Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology and Visual Science Key Laboratory, Beijing, China. ·Surv Ophthalmol · Pubmed #26164737.

ABSTRACT: Primary angle closure disease (PACD), prevalent in Asian countries, is generally associated with a shallower anterior chamber, a shorter axial length, thicker lens, hyperopia, and female sex. Other physiologic factors, however, may be important, especially with regard to triggering acute primary angle closure. Thickening of the choroid has been demonstrated in untreated and treated, acute and chronic PACD eyes. Recently, there has been growing interest in studying the role of the choroid in the pathophysiology of PACD. The emergence of new imaging technology such as the enhanced depth imaging mode of spectral-domain optical coherence tomography and swept-source optical coherence tomography has contributed to understanding PACD pathologies. We summarize the functions of the choroid and choroidal changes in the pathogenesis of PACD, and discuss potential future developments.

10 Review The role of lens extraction in the current management of primary angle-closure glaucoma. 2015

Trikha, Sameer / Perera, Shamira A / Husain, Rahat / Aung, Tin. ·aSingapore Eye Research Institute, Singapore National Eye Centre bDuke-NUS Graduate Medical School cDepartment of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. ·Curr Opin Ophthalmol · Pubmed #25565368.

ABSTRACT: PURPOSE OF REVIEW: Lens extraction for primary angle-closure glaucoma (PACG) is a subject of increased interest recently, with advocates promoting its benefits of anatomical opening of the angle, intraocular pressure (IOP) reduction and improved vision. The present review seeks to evaluate recent available evidence to provide clarity on this potential intervention within the armamentarium of approaches for PACG. RECENT FINDINGS: The emergence of recent case-control studies, cohort studies and randomized controlled trials has provided a stronger evidence base to equip ophthalmic surgeons with the necessary information to utilize lens extraction in the management of PACG, and to consider whether this should be combined with trabeculectomy or goniosynechialysis. Imaging modalities such as anterior segment optical coherence tomography have yielded new insights into the mechanical features of the lens in angle closure, with the lens thickness and lens vault now quantifiable. A trend is emerging regarding the improvement in IOP control, reduced complication rates and reduced need for IOP-lowering medications in patients who undergo lens extraction for PACG. These issues are discussed, along with aspects of preoperative assessment and surgical techniques. SUMMARY: Good outcomes in terms of long-term IOP control have been found following lens extraction for PACG. Lens extraction should be considered in patients with PACG, especially with hyperopia, or a thick and anteriorly vaulted lens.

11 Review Global prevalence of glaucoma and projections of glaucoma burden through 2040: a systematic review and meta-analysis. 2014

Tham, Yih-Chung / Li, Xiang / Wong, Tien Y / Quigley, Harry A / Aung, Tin / Cheng, Ching-Yu. ·Singapore Eye Research Institute, Singapore National Eye Centre, Singapore; Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore. · Singapore Eye Research Institute, Singapore National Eye Centre, Singapore; Department of Statistics and Applied Probability, National University of Singapore, Singapore. · Glaucoma Service and Dana Center for Preventive Ophthalmology, Wilmer Ophthalmological Institute, Johns Hopkins School of Medicine, Baltimore, Maryland. · Singapore Eye Research Institute, Singapore National Eye Centre, Singapore; Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore; Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore; Duke-NUS Graduate Medical School, Singapore. Electronic address: ching-yu_cheng@nuhs.edu.sg. ·Ophthalmology · Pubmed #24974815.

ABSTRACT: PURPOSE: Glaucoma is the leading cause of global irreversible blindness. Present estimates of global glaucoma prevalence are not up-to-date and focused mainly on European ancestry populations. We systematically examined the global prevalence of primary open-angle glaucoma (POAG) and primary angle-closure glaucoma (PACG), and projected the number of affected people in 2020 and 2040. DESIGN: Systematic review and meta-analysis. PARTICIPANTS: Data from 50 population-based studies (3770 POAG cases among 140,496 examined individuals and 786 PACG cases among 112 398 examined individuals). METHODS: We searched PubMed, Medline, and Web of Science for population-based studies of glaucoma prevalence published up to March 25, 2013. Hierarchical Bayesian approach was used to estimate the pooled glaucoma prevalence of the population aged 40-80 years along with 95% credible intervals (CrIs). Projections of glaucoma were estimated based on the United Nations World Population Prospects. Bayesian meta-regression models were performed to assess the association between the prevalence of POAG and the relevant factors. MAIN OUTCOME MEASURES: Prevalence and projection numbers of glaucoma cases. RESULTS: The global prevalence of glaucoma for population aged 40-80 years is 3.54% (95% CrI, 2.09-5.82). The prevalence of POAG is highest in Africa (4.20%; 95% CrI, 2.08-7.35), and the prevalence of PACG is highest in Asia (1.09%; 95% CrI, 0.43-2.32). In 2013, the number of people (aged 40-80 years) with glaucoma worldwide was estimated to be 64.3 million, increasing to 76.0 million in 2020 and 111.8 million in 2040. In the Bayesian meta-regression model, men were more likely to have POAG than women (odds ratio [OR], 1.36; 95% CrI, 1.23-1.52), and after adjusting for age, gender, habitation type, response rate, and year of study, people of African ancestry were more likely to have POAG than people of European ancestry (OR, 2.80; 95% CrI, 1.83-4.06), and people living in urban areas were more likely to have POAG than those in rural areas (OR, 1.58; 95% CrI, 1.19-2.04). CONCLUSIONS: The number of people with glaucoma worldwide will increase to 111.8 million in 2040, disproportionally affecting people residing in Asia and Africa. These estimates are important in guiding the designs of glaucoma screening, treatment, and related public health strategies.

12 Review The pathophysiology and treatment of glaucoma: a review. 2014

Weinreb, Robert N / Aung, Tin / Medeiros, Felipe A. ·Hamilton Glaucoma Center, Shiley Eye Center and Department of Ophthalmology, University of California, San Diego, La Jolla. · Singapore National Eye Center, Singapore, Singapore3Yong Loo Lin School of Medicine, National University of Singapore, Singapore. ·JAMA · Pubmed #24825645.

ABSTRACT: IMPORTANCE: Glaucoma is a worldwide leading cause of irreversible vision loss. Because it may be asymptomatic until a relatively late stage, diagnosis is frequently delayed. A general understanding of the disease pathophysiology, diagnosis, and treatment may assist primary care physicians in referring high-risk patients for comprehensive ophthalmologic examination and in more actively participating in the care of patients affected by this condition. OBJECTIVE: To describe current evidence regarding the pathophysiology and treatment of open-angle glaucoma and angle-closure glaucoma. EVIDENCE REVIEW: A literature search was conducted using MEDLINE, the Cochrane Library, and manuscript references for studies published in English between January 2000 and September 2013 on the topics open-angle glaucoma and angle-closure glaucoma. From the 4334 abstracts screened, 210 articles were selected that contained information on pathophysiology and treatment with relevance to primary care physicians. FINDINGS: The glaucomas are a group of progressive optic neuropathies characterized by degeneration of retinal ganglion cells and resulting changes in the optic nerve head. Loss of ganglion cells is related to the level of intraocular pressure, but other factors may also play a role. Reduction of intraocular pressure is the only proven method to treat the disease. Although treatment is usually initiated with ocular hypotensive drops, laser trabeculoplasty and surgery may also be used to slow disease progression. CONCLUSIONS AND RELEVANCE: Primary care physicians can play an important role in the diagnosis of glaucoma by referring patients with positive family history or with suspicious optic nerve head findings for complete ophthalmologic examination. They can improve treatment outcomes by reinforcing the importance of medication adherence and persistence and by recognizing adverse reactions from glaucoma medications and surgeries.

13 Review Angle closure and angle-closure glaucoma: what we are doing now and what we will be doing in the future. 2012

Friedman, David S / Foster, Paul J / Aung, Tin / He, Mingguang. ·Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. ·Clin Exp Ophthalmol · Pubmed #22356460.

ABSTRACT: Primary angle-closure glaucoma (PACG) frequently leads to severe vision loss. Prevalence among older Asian populations is high and given global demographics, the number of persons with PACG will increase dramatically in the coming decades. Improvements in imaging of the anterior segment will help us to identify more of those with angle closure, and important clinical trials that are currently underway will provide important evidence to support screening and treatment approaches for PACG. In this manuscript, we intend to review the existing evidences, to introduce some important on-going studies on PACG and to share the experience and viewpoints of the authors.

14 Review Angle closure glaucoma: a mechanistic review. 2011

Nongpiur, Monisha E / Ku, Judy Y F / Aung, Tin. ·Singapore National Eye Centre & Singapore Eye Research Institute, Singapore. ·Curr Opin Ophthalmol · Pubmed #21252671.

ABSTRACT: PURPOSE OF REVIEW: With recent advances in imaging techniques such as anterior segment optical coherence tomography and ultrasound biomicroscopy, there is a better understanding of nonpupil block mechanisms and novel risk factors contributing to the pathogenesis of angle closure glaucoma. RECENT FINDINGS: Recent studies suggest that multiple anatomical and physiological factors interplay in the pathogenesis of angle closure glaucoma. The association of greater iris convexity, area and thickness with narrow angles could result in a more anterior bowing and crowding of the peripheral iris. Other novel anatomic parameters such as greater lens vault, smaller anterior chamber width, area and volume, independently increase the risk of having angle closure. Dynamic increase or lesser reduction in iris volume during dilation supports the theory of physiological predisposition to the disease process. Choroidal expansion has been demonstrated in untreated and treated, acute and chronic primary angle closure eyes. It remains unknown whether this finding is a cause or effect in this condition. SUMMARY: With a wider availability of imaging tools and a better understanding of risk factors and mechanisms, clinicians maybe able to more accurately identify those at greater risk of developing angle closure disease and tailor their treatment according to the predominant factor(s) involved.

15 Review Angle imaging: advances and challenges. 2011

Quek, Desmond T L / Nongpiur, Monisha E / Perera, Shamira A / Aung, Tin. ·Singapore National Eye Centre, Singapore Eye Research Institute and Yong Loo Lin School of Medicine, National University of Singapore, Singapore. ·Indian J Ophthalmol · Pubmed #21150037.

ABSTRACT: Primary angle closure glaucoma (PACG) is a major form of glaucoma in large populous countries in East and South Asia. The high visual morbidity from PACG is related to the destructive nature of the asymptomatic form of the disease. Early detection of anatomically narrow angles is important and the subsequent prevention of visual loss from PACG depends on an accurate assessment of the anterior chamber angle (ACA). This review paper discusses the advantages and limitations of newer ACA imaging technologies, namely ultrasound biomicroscopy, Scheimpflug photography, anterior segment optical coherence tomography and EyeCam, highlighting the current clinical evidence comparing these devices with each other and with clinical dynamic indentation gonioscopy, the current reference standard.

16 Article Laser peripheral iridotomy for the prevention of angle closure: a single-centre, randomised controlled trial. 2019

He, Mingguang / Jiang, Yuzhen / Huang, Shengsong / Chang, Dolly S / Munoz, Beatriz / Aung, Tin / Foster, Paul J / Friedman, David S. ·State Key Laboratory of Ophthalmology, Clinical Research Center, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, China; Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, East Melbourne, VIC, Australia; National Institute for Health Research Biomedical Research Centre, Moorfields Eye Hospital, London, UK; UCL Institute of Ophthalmology, London, UK. Electronic address: mingguang_he@yahoo.com. · National Institute for Health Research Biomedical Research Centre, Moorfields Eye Hospital, London, UK; UCL Institute of Ophthalmology, London, UK. · State Key Laboratory of Ophthalmology, Clinical Research Center, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, China. · Dana Center for Preventive Ophthalmology, Wilmer Eye Institute and Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. · Singapore Eye Research Institute, Singapore National Eye Centre, Singapore Yong Loo Lin School of Medicine, National University of Singapore, Singapore. · National Institute for Health Research Biomedical Research Centre, Moorfields Eye Hospital, London, UK; UCL Institute of Ophthalmology, London, UK. Electronic address: p.foster@ucl.ac.uk. ·Lancet · Pubmed #30878226.

ABSTRACT: BACKGROUND: Primary angle-closure glaucoma affects 20 million people worldwide. People classified as primary angle closure suspects have a higher but poorly quantified risk of developing glaucoma. We aimed to assess efficacy and safety of laser peripheral iridotomy prophylaxis against primary angle-closure glaucoma in Chinese people classified as primary angle closure suspects. METHODS: In this randomised controlled trial, bilateral primary angle closure suspects aged 50-70 years were enrolled at the Zhongshan Ophthalmic Center, a tertiary specialised hospital in Guangzhou, China. Eligible patients received laser peripheral iridotomy in one randomly selected eye, with the other remaining untreated. The primary outcome was incident primary angle closure disease as a composite endpoint of elevation of intraocular pressure, peripheral anterior synechiae, or acute angle-closure during 72 months of follow-up in an intention-to-treat analysis between treated eyes and contralateral controls. This trial is registered with the ISRCTN registry, number ISRCTN45213099. FINDINGS: Of 11 991 screened individuals, 889 individuals were randomly assigned from June 19, 2008 (889 treated and 889 untreated eyes). Incidence of the primary outcome was 4·19 per 1000 eye-years in treated eyes compared with 7·97 per 1000 eye-years in untreated eyes (hazard ratio 0·53; 95% CI 0·30-0·92; p=0·024). A primary outcome event occurred in 19 treated eyes and 36 untreated eyes with a statistically significant difference using pair-wise analysis (p=0·0041). No serious adverse events were observed during follow-up. INTERPRETATION: Incidence of angle-closure disease was very low among individuals classified as primary angle closure suspects identified through community-based screening. Laser peripheral iridotomy had a modest, albeit significant, prophylactic effect. In view of the low incidence rate of outcomes that have no immediate threat to vision, the benefit of prophylactic laser peripheral iridotomy is limited; therefore, widespread prophylactic laser peripheral iridotomy for primary angle-closure suspects is not recommended. FUNDING: Fight for Sight, the Sun Yat-Sen University 5010 Project Fund, Moorfields Eye Charity, and the National Natural Science Foundation of China.

17 Article Characteristics of the Corneal Endothelium Across the Primary Angle Closure Disease Spectrum. 2018

Verma, Sushma / Nongpiur, Monisha E / Husain, Rahat / Wong, Tina T / Boey, Pui Yi / Quek, Desmond / Perera, Shamira A / Aung, Tin. ·Singapore Eye Research Institute, Singapore National Eye Centre, Singapore. · Duke-NUS Graduate Medical School, Singapore. · Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. ·Invest Ophthalmol Vis Sci · Pubmed #30208420.

ABSTRACT: Purpose: To evaluate the corneal endothelial characteristics across the primary angle closure (PAC) disease spectrum amongst patients diagnosed as PAC suspects (PACS), PAC, PAC glaucoma (PACG), and previous acute PAC (APAC). Methods: We analyzed a total of 529 subjects (51 PACS, 170 PAC, 234 PACG, and 74 with previous APAC). All subjects had undergone laser peripheral iridotomy prior to study recruitment. Corneal endothelial parameters were measured using a noncontact specular microscope and the following parameters were obtained: mean central endothelial cell density (ECD; cells/mm2), coefficient of variation (CV) in cell area, and percentage of hexagonal cells. Results: The mean age of the subjects was 65.1 ± 8.2 years, and 55.2% were females. The mean central ECD was 2582.0 ± 472.8 cells/mm2 in PACS, 2566.0 ± 408.3 cells/mm2 in PAC, 2523.8 ± 406.8 cells/mm2 in PACG, and 2504.0 ± 558.1 cells/mm2 in APAC, with no significant differences in ECD across the subgroups (P = 0.61). The CV was lowest in PACS (34.38 ± 6.05 μm2/cell), and highest in APAC (37.61 ± 7.98 μm2/cell), but the differences were not significant (P = 0.07). Likewise, the percentage of hexagonality was not significantly different between the groups. A subgroup analysis on the eyes with previous APAC with their fellow eye also showed no significant differences in the corneal endothelial characteristics. Conclusions: The corneal ECD and morphological characteristics such as CV and hexagonality are not significantly different across the PAC disease spectrum. This may reflect the lack of a sustained and/or dramatic IOP insult and/or an insignificant deleterious effect from medications, age, and chronicity on corneal endothelial parameters.

18 Article Diagnostic accuracy of macular ganglion cell-inner plexiform layer thickness for glaucoma detection in a population-based study: Comparison with optic nerve head imaging parameters. 2018

Koh, Victor / Tham, Yih-Chung / Cheung, Carol Y / Mani, Baskaran / Wong, Tien Yin / Aung, Tin / Cheng, Ching-Yu. ·Singapore Eye Research Institute, Singapore National Eye Centre, Singapore. · Department of Ophthalmology, National University Health System, Singapore. · Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China. · Duke-NUS Graduate Medical School Singapore, Singapore. · Yong Loo Lin School of Medicine, National University of Singapore. ·PLoS One · Pubmed #29944673.

ABSTRACT: AIMS: To determine the diagnostic performance of macular ganglion cell-inner plexiform layer (GCIPL) thickness measured by spectral-domain optical coherence tomography (SD-OCT) for glaucoma detection in a Chinese population in comparison with optic nerve head (ONH) and retinal nerve fiber layer (RNFL) parameters measured by both SD-OCT and Heidelberg Retina Tomography 3 (HRT-3). METHODS: Adults aged 40 to 80 years were recruited from the population-based study (n = 3353, response rate 72.8%). Macular cube 200x200 scan was performed with Cirrus SD-OCT (version 6.0, Carl Zeiss Meditec Inc, Dublin, CA) for GCIPL thickness measurement. ONH and RNFL imaging was performed with Cirrus SD-OCT and HRT-3 (Heidelberg Engineering, Heidelberg, Germany). Glaucoma was defined according to International Society for Geographical and Epidemiological Ophthalmology criteria. RESULTS: In total, 86 eyes of 60 subjects with glaucoma and 1709 eyes of 1001 non-glaucoma participants were included. The best performing parameters for Cirrus SD-OCT GCIPL, Cirrus SD-OCT ONH and HRT-3 were minimum GCIPL thickness (Area under receiver-operating curve [AUC] = 0.89, 95% CI 0.83-0.95), vertical cup-disc ratio (CDR) (AUC = 0.94, 0.91-0.98) and vertical CDR (AUC = 0.86, 0.81-0.92), respectively. At 85% specificity, vertical CDR measured using Cirrus OCT ONH scan showed the highest sensitivity (88.64%, 95% CI 75.4-96.2) compared to minimum GCIPL thickness with sensitivity of 60.53% (95% CI 46.4-73.0) (p<0.001). Inferior RNFL thickness (AUC = 0.84, 95% CI 0.91-0.97) measured by Cirrus SD-OCT was also superior to Cirrus SD-OCT GCIPL (p<0.007). CONCLUSIONS: The diagnostic performance of macular GCIPL scan is inferior compared to vertical CDR measured by Cirrus OCT ONH scan. Cirrus OCT ONH scan showed the best ability in detecting glaucoma in a Chinese population, suggesting it could be a good glaucoma screening tool in an Asian population.

19 Article Cross-ancestry genome-wide association analysis of corneal thickness strengthens link between complex and Mendelian eye diseases. 2018

Iglesias, Adriana I / Mishra, Aniket / Vitart, Veronique / Bykhovskaya, Yelena / Höhn, René / Springelkamp, Henriët / Cuellar-Partida, Gabriel / Gharahkhani, Puya / Bailey, Jessica N Cooke / Willoughby, Colin E / Li, Xiaohui / Yazar, Seyhan / Nag, Abhishek / Khawaja, Anthony P / Polašek, Ozren / Siscovick, David / Mitchell, Paul / Tham, Yih Chung / Haines, Jonathan L / Kearns, Lisa S / Hayward, Caroline / Shi, Yuan / van Leeuwen, Elisabeth M / Taylor, Kent D / Anonymous9241162 / Bonnemaijer, Pieter / Rotter, Jerome I / Martin, Nicholas G / Zeller, Tanja / Mills, Richard A / Souzeau, Emmanuelle / Staffieri, Sandra E / Jonas, Jost B / Schmidtmann, Irene / Boutin, Thibaud / Kang, Jae H / Lucas, Sionne E M / Wong, Tien Yin / Beutel, Manfred E / Wilson, James F / Anonymous9251162 / Anonymous9261162 / Uitterlinden, André G / Vithana, Eranga N / Foster, Paul J / Hysi, Pirro G / Hewitt, Alex W / Khor, Chiea Chuen / Pasquale, Louis R / Montgomery, Grant W / Klaver, Caroline C W / Aung, Tin / Pfeiffer, Norbert / Mackey, David A / Hammond, Christopher J / Cheng, Ching-Yu / Craig, Jamie E / Rabinowitz, Yaron S / Wiggs, Janey L / Burdon, Kathryn P / van Duijn, Cornelia M / MacGregor, Stuart. ·Department of Ophthalmology, Erasmus Medical Center, 3000 CA, Rotterdam, The Netherlands. · Department of Epidemiology, Erasmus Medical Center, 3000 CA, Rotterdam, The Netherlands. · Department of Clinical Genetics, Erasmus Medical Center, 3000 CA, Rotterdam, The Netherlands. · University of Bordeaux, Bordeaux Population Health Research Center, INSERM UMR 1219, F-33000, Bordeaux, France. · Institute of Genetics and Molecular Medicine, Medical Research Council Human Genetics Unit, University of Edinburgh, EH42XU, Edinburgh, UK. · Regenerative Medicine Institute and Department of Surgery, Cedars-Sinai Medical Center, CA 90048, Los Angeles, CA, USA. · Cornea Genetic Eye Institute, CA 90048, Los Angeles, CA, USA. · Department of Ophthalmology, University Medical Center Mainz, 55131, Mainz, Germany. · Department of Ophthalmology, Inselspital, University Hospital Bern, University of Bern, Bern, CH-3010, Switzerland. · Statistical Genetics, QIMR Berghofer Medical Research Institute, QLD 4029, Brisbane, Australia. · Department of Population and Quantitative Health Sciences, Case Western Reserve University, OH 44106, Cleveland, OH, USA. · Institute for Computational Biology, Case Western Reserve University, Cleveland, OH, 44106, USA. · Biomedical Sciences Research Institute, Ulster University, BT52 1SA, Belfast, Northern Ireland, UK. · Royal Victoria Hospital, Belfast Health and Social Care Trust, BT12 6BA, Belfast, Northern Ireland, UK. · Institute for Translational Genomics and Population Sciences and Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA 90509, CA, USA. · Division of Genomic Outcomes, Departments of Pediatrics and Medicine, Harbor-UCLA Medical Center, Torrance, CA 90502, CA, USA. · Centre for Ophthalmology and Visual Science, University of Western Australia, Lions Eye Institute, WA 6009, Perth, WA, Australia. · Department of Twin Research and Genetic Epidemiology, King's College London, WC2R 2LS, London, UK. · Department of Public Health and Primary Care, Institute of Public Health, University of Cambridge School of Clinical Medicine, CB2 0SR, Cambridge, UK. · NIHR Biomedical Research Centre, Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, EC1V 9EL, London, UK. · Faculty of Medicine, University of Split, HR-21000, Split, Croatia. · Departments of Medicine and Epidemiology and Cardiovascular Health Research Unit, University of Washington, WA 98101, Washington, USA. · The New York Academy of Medicine, NY 10029, New York, NY, USA. · Centre for Vision Research, Department of Ophthalmology and Westmead Institute for Medical Research, University of Sydney, NSW 2145, Sydney, NSW, Australia. · Singapore Eye Research Institute, Singapore National Eye Centre, 168751, Singapore, Singapore. · Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, VIC 3002, East Melbourne, Australia. · Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, QLD 4029, Brisbane, Australia. · Department of General and Interventional Cardiology, University Heart Center Hamburg, 20251, Hamburg, Germany. · German Center for Cardiovascular Research (DZHK), Partner Site Hamburg/Kiel/Lübeck, 20246, Hamburg, Germany. · Department of Ophthalmology, Flinders University, SA 5042, Adelaide, Australia. · Department of Ophthalmology, Medical Faculty Mannheim of the Ruprecht-Karls-University of Heidelberg, 68167, Mannheim, Germany. · Institute for Medical Biostatistics, Epidemiology and Informatics, University Medical Center Mainz, 55131, Mainz, Germany. · Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA 02115, MA, USA. · Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS 7005, TAS, Australia. · Ophthalmology & Visual Sciences Academic Clinical Program (Eye ACP), Duke-NUS Medical School, 169857, Singapore, Singapore. · Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117549, Singapore. · Department of Psychosomatic Medicine and Psychotherapy, University Medical Center Mainz, Mainz, 55131, Germany. · Centre for Global Health Research, Usher Institute for Population Health Sciences and Informatics, University of Edinburgh, EH16 4UX, Edinburgh, UK. · Department of Internal Medicine, Erasmus Medical Center, 3000 CA, Rotterdam, The Netherlands. · Netherlands Consortium for Healthy Ageing, Netherlands Genomics Initiative, 2593 HW, The Hague, The Netherlands. · School of Medicine, Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS 7005, TAS, Australia. · Genome Institute of Singapore, 60 Biopolis Street, Singapore, 138672, Singapore. · Department of Ophthalmology, Harvard Medical School and Massachusetts Eye and Ear Infirmary, Boston, MA 02114, MA, USA. · Institute for Molecular Bioscience, University of Queensland, QLD 4067, Brisbane, Australia. · Department of Ophthalmology, Radboud University Medical Center, 6525 GA, Nijmegen, The Netherlands. · Statistical Genetics, QIMR Berghofer Medical Research Institute, QLD 4029, Brisbane, Australia. Stuart.MacGregor@qimrberghofer.edu.au. ·Nat Commun · Pubmed #29760442.

ABSTRACT: Central corneal thickness (CCT) is a highly heritable trait associated with complex eye diseases such as keratoconus and glaucoma. We perform a genome-wide association meta-analysis of CCT and identify 19 novel regions. In addition to adding support for known connective tissue-related pathways, pathway analyses uncover previously unreported gene sets. Remarkably, >20% of the CCT-loci are near or within Mendelian disorder genes. These included FBN1, ADAMTS2 and TGFB2 which associate with connective tissue disorders (Marfan, Ehlers-Danlos and Loeys-Dietz syndromes), and the LUM-DCN-KERA gene complex involved in myopia, corneal dystrophies and cornea plana. Using index CCT-increasing variants, we find a significant inverse correlation in effect sizes between CCT and keratoconus (r = -0.62, P = 5.30 × 10

20 Article Anterior Choroidal Thickness Increased in Primary Open-Angle Glaucoma and Primary Angle-Closure Disease Eyes Evidenced by Ultrasound Biomicroscopy and SS-OCT. 2018

Gao, Kai / Li, Fei / Li, Yingqi / Li, Xingyi / Huang, Wenbin / Chen, Shida / Liu, Yaoming / Aung, Tin / Zhang, Xiulan. ·State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China. · Singapore Eye Research Institute, Singapore National Eye Centre, Singapore. ·Invest Ophthalmol Vis Sci · Pubmed #29625448.

ABSTRACT: Purpose: To compare the anterior and posterior choroid thickness (ACT and PCT, respectively) in primary open-angle glaucoma (POAG), primary angle-closure disease (PACD), and healthy control subjects. Methods: A total of 29 POAG patients (56 eyes), 37 PACD patients (64 eyes), and 34 healthy volunteers (68 eyes) were enrolled in this study; 50 POAG eyes were divided into 25 early/moderate-stage and 25 advanced-stage eyes by visual field loss, while 64 PACD eyes were classified as primary angle-closure suspect (PACS), 8 eyes; primary angle closure (PAC), 18 eyes; and primary angle-closure glaucoma (PACG), 38 eyes. Ultrasound biomicroscopy (UBM) was used to measure the ACT at a distance of 4 mm from the root of iris in all participants. ACT and PCT were measured using UBM and swept-source optical coherence tomography (SS-OCT), respectively. A 4-mm distance from the iris root was self-defined as the anterior choroid that well matched the real anterior choroid. Results: The mean ACT measured by UBM was 0.45 ± 0.057 mm in POAG eyes, 0.38 ± 0.050 mm in PACD eyes, and 0.30 ± 0.050 mm in healthy eyes. Both the POAG and PACD eyes had a thicker anterior choroid than healthy eyes (P < 0.01). Compared to early/moderate-stage eyes of POAG, advanced-stage eyes had similar ACT (P > 0.05). PACG eyes had a thinner anterior choroid than PAC/PACS eyes (P < 0.05). However, no statistically significant difference was noted for POAG, PACD, and normal control eyes' PCT using SS-OCT (P > 0.05). Conclusions: POAG/PACD eyes had a thicker anterior choroid than the controls. However, there was no significant difference in the PCT among the groups. The anterior choroid might play a role in the pathogenesis of glaucoma, warranting further investigation.

21 Article Clear lens extraction for the management of primary angle closure glaucoma: surgical technique and refractive outcomes in the EAGLE cohort. 2018

Day, Alexander C / Cooper, David / Burr, Jennifer / Foster, Paul J / Friedman, David S / Gazzard, Gus / Che-Hamzah, Jemaima / Aung, Tin / Ramsay, Craig R / Azuara-Blanco, Augusto. ·NIHR Biomedical Research Centre, Moorfields Eye Hospital and University College London, London, UK. · Health Services Research Unit, University of Aberdeen, Aberdeen, UK. · School of Medicine, University of St Andrews, St Andrews, UK. · John Hopkins Wilmer Eye Institute, Baltimore, Maryland, USA. · Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia. · Singapore Eye Research Institute, Singapore. · Centre for Public Health, Queen's University Belfast, Belfast, UK. ·Br J Ophthalmol · Pubmed #29453222.

ABSTRACT: BACKGROUND: To describe the surgical technique and refractive outcomes following clear lens extraction (CLE) in the Effectiveness, in Angle-closure Glaucoma, of Lens Extraction trial. METHODS: Review of prospectively collected data from a multicentre, randomised controlled trial comparing CLE and laser peripheral iridotomy. Eligible participants were ≥50 years old and newly diagnosed with (1) primary angle closure (PAC) with intraocular pressure above 30 mm Hg or (2) PAC glaucoma. We report the postoperative corrected distance visual acuity (CDVA) and refractive outcomes at 12 and 36 months postoperatively for those who underwent CLE. RESULTS: Of the 419 participants, 208 were randomised to CLE. Mean baseline CDVA was 77.9 (SD 12.4) letters and did not change significantly at 36 months when mean CDVA was 79.9 (SD 10.9) letters. Mean preoperative spherical equivalents were +1.7 (SD 2.3) and +0.08 (SD 0.95) diopters (D) at 36 months. Fifty-nine per cent and 85% eyes were within ±0.5D and ±1.0D of predicted refraction, respectively, at 36 months. CONCLUSIONS: Mean CDVA in patients undergoing CLE for angle-closure glaucoma appeared stable over the 3-year study period. Refractive error was significantly reduced with surgery but refractive predictability was suboptimal.

22 Article Genome-wide association study identifies seven novel susceptibility loci for primary open-angle glaucoma. 2018

Shiga, Yukihiro / Akiyama, Masato / Nishiguchi, Koji M / Sato, Kota / Shimozawa, Nobuhiro / Takahashi, Atsushi / Momozawa, Yukihide / Hirata, Makoto / Matsuda, Koichi / Yamaji, Taiki / Iwasaki, Motoki / Tsugane, Shoichiro / Oze, Isao / Mikami, Haruo / Naito, Mariko / Wakai, Kenji / Yoshikawa, Munemitsu / Miyake, Masahiro / Yamashiro, Kenji / Anonymous391123 / Kashiwagi, Kenji / Iwata, Takeshi / Mabuchi, Fumihiko / Takamoto, Mitsuko / Ozaki, Mineo / Kawase, Kazuhide / Aihara, Makoto / Araie, Makoto / Yamamoto, Tetsuya / Kiuchi, Yoshiaki / Nakamura, Makoto / Ikeda, Yasuhiro / Sonoda, Koh-Hei / Ishibashi, Tatsuro / Nitta, Koji / Iwase, Aiko / Shirato, Shiroaki / Oka, Yoshitaka / Satoh, Mamoru / Sasaki, Makoto / Fuse, Nobuo / Suzuki, Yoichi / Cheng, Ching-Yu / Khor, Chiea Chuen / Baskaran, Mani / Perera, Shamira / Aung, Tin / Vithana, Eranga N / Cooke Bailey, Jessica N / Kang, Jae H / Pasquale, Louis R / Haines, Jonathan L / Anonymous401123 / Wiggs, Janey L / Burdon, Kathryn P / Gharahkhani, Puya / Hewitt, Alex W / Mackey, David A / MacGregor, Stuart / Craig, Jamie E / Allingham, R Rand / Hauser, Micheal / Ashaye, Adeyinka / Budenz, Donald L / Akafo, Stephan / Williams, Susan E I / Kamatani, Yoichiro / Nakazawa, Toru / Kubo, Michiaki. ·Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan. · Department of Ophthalmology, Tohoku University Graduate School of Medicine, Miyagi, Japan. · Department of Advanced Ophthalmic Medicine, Tohoku University Graduate School of Medicine, Miyagi, Japan. · Department of Ophthalmic Imaging and Information Analytics, Tohoku University Graduate School of Medicine, Miyagi, Japan. · Tsukuba Primate Research Center, National Institutes of Biomedical Innovation, Health and Nutrition, Ibaraki, Japan. · Omics Research Center, National Cerebral and Cardiovascular Center, Osaka, Japan. · Laboratory for Genotyping Development, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan. · Institute of Medical Science, The University of Tokyo, Tokyo, Japan. · Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan. · Division of Epidemiology, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan. · Center for Public Health Sciences, National Cancer Center, Tokyo, Japan. · Division of Molecular and Clinical Epidemiology, Aichi Cancer Center Research Institute, Nagoya, Japan. · Cancer Prevention Center, Chiba Cancer Center Research Institute, Chiba, Japan. · Department of Preventive Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan. · Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan. · Department of Ophthalmology, Otsu Red-Cross Hospital, Otsu, Japan. · Department of Ophthalmology, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan. · Division of Molecular and Cellular Biology, National Institute of Sensory Organs, Tokyo Medical Center, National Hospital Organization, Tokyo, Japan. · Department of Ophthalmology, University of Tokyo, Tokyo, Japan. · Ozaki Eye Hospital, Hyuga, Miyazaki, Japan. · Department of Ophthalmology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan. · Department of Ophthalmology, Gifu University Graduate School of Medicine, Gifu, Japan. · Kanto Central Hospital of the Mutual Aid Association of Public School Teachers, Tokyo, Japan. · Department of Ophthalmology and Visual Sciences, Hiroshima University, Hiroshima, Japan. · Division of Ophthalmology, Department of Surgery, Kobe University Graduate School of Medicine, Kobe, Japan. · Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. · Fukuiken Saiseikai Hospital, Fukui, Japan. · Tajimi Iwase Eye Clinic, Tajimi, Japan. · Yotsuya Shirato Eye Clinic, Tokyo, Japan. · Oka Eye Clinic, Fukuoka, Japan. · Iwate Tohoku Medical Megabank Organization, Iwate Medical University, Iwate, Japan. · Department of Integrative Genomics, Tohoku Medical Megabank Organization, Miyagi, Japan. · Department of Education and Training, Tohoku Medical Megabank Organization, Miyagi, Japan. · Singapore Eye Research Institute, Singapore National Eye Centre, Singapore. · Ophthalmology and Visual Sciences Academic Clinical Program (Eye ACP), Duke-NUS Medical School, Singapore. · Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. · Genome Institute of Singapore, Singapore. · Department of Population and Quantitative Health Sciences, Institute for Computational Biology, Case Western Reserve University School of Medicine, Cleveland, OH, USA. · Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA. · Department of Ophthalmology, Harvard Medical School, Boston, MA, USA. · Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia. · Department of Ophthalmology, Flinders University, Adelaide, SA, Australia. · QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia. · Centre for Eye Research Australia, University of Melbourne, Melbourne, VIC, Australia. · Department of Ophthalmology, Royal Victorian Eye and Ear Hospital, Melbourne, VIC, Australia. · Centre for Ophthalmology and Visual Science, Lions Eye Institute, University of Western Australia, Perth, WA, Australia. · Department of Ophthalmology, Duke University, Durham, NC, USA. · Duke University Medical Center, Durham, NC, USA. · Department of Ophthalmology, College of Medicine, University of Ibadan, Ibadan, Nigeria. · Department of Ophthalmology, University of North Carolina at Chapel Hill, USA. · University of Ghana School of Medicine and Dentistry, Ghana. · Division of Ophthalmology, Department of Neurosciences, University of the Witwatersrand, South Africa. · Center for Genomic Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan. ·Hum Mol Genet · Pubmed #29452408.

ABSTRACT: Primary open-angle glaucoma (POAG) is the leading cause of irreversible blindness worldwide for which 15 disease-associated loci had been discovered. Among them, only 5 loci have been associated with POAG in Asians. We carried out a genome-wide association study and a replication study that included a total of 7378 POAG cases and 36 385 controls from a Japanese population. After combining the genome-wide association study and the two replication sets, we identified 11 POAG-associated loci, including 4 known (CDKN2B-AS1, ABCA1, SIX6 and AFAP1) and 7 novel loci (FNDC3B, ANKRD55-MAP3K1, LMX1B, LHPP, HMGA2, MEIS2 and LOXL1) at a genome-wide significance level (P < 5.0×10-8), bringing the total number of POAG-susceptibility loci to 22. The 7 novel variants were subsequently evaluated in a multiethnic population comprising non-Japanese East Asians (1008 cases, 591 controls), Europeans (5008 cases, 35 472 controls) and Africans (2341 cases, 2037 controls). The candidate genes located within the new loci were related to ocular development (LMX1B, HMGA2 and MAP3K1) and glaucoma-related phenotypes (FNDC3B, LMX1B and LOXL1). Pathway analysis suggested epidermal growth factor receptor signaling might be involved in POAG pathogenesis. Genetic correlation analysis revealed the relationships between POAG and systemic diseases, including type 2 diabetes and cardiovascular diseases. These results improve our understanding of the genetic factors that affect the risk of developing POAG and provide new insight into the genetic architecture of POAG in Asians.

23 Article In Vivo Three-Dimensional Lamina Cribrosa Strains in Healthy, Ocular Hypertensive, and Glaucoma Eyes Following Acute Intraocular Pressure Elevation. 2018

Beotra, Meghna R / Wang, Xiaofei / Tun, Tin A / Zhang, Liang / Baskaran, Mani / Aung, Tin / Strouthidis, Nicholas G / Girard, Michaël J A. ·Ophthalmic Engineering & Innovation Laboratory, Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore, Singapore. · Singapore Eye Research Institute, Singapore National Eye Centre, Singapore. · Duke-NUS Medical School, Singapore. · Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. · NIHR Biomedical Research Centre, Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, United Kingdom. · Discipline of Clinical Ophthalmology and Eye Health, University of Sydney, Sydney, New South Wales, Australia. ·Invest Ophthalmol Vis Sci · Pubmed #29340640.

ABSTRACT: Purpose: To compare in vivo lamina cribrosa (LC) strains (deformations) following acute IOP elevation in healthy, glaucoma, and ocular hypertensive subjects. Methods: There were 20 healthy, 20 high-tension primary open-angle glaucoma (POAG), 16 primary angle-closure glaucoma (PACG), and 20 ocular hypertensive (OHT; with normal visual fields) eyes studied. For each test eye, the optic nerve head was imaged three times (at baseline IOP, following an acute elevation of IOP to approximately 35 then 45 mm Hg using an ophthalmodynamomter) using optical coherence tomography (OCT). A three-dimensional (3D) strain-mapping algorithm was applied to both sets of baseline and IOP-elevated OCT volumes to extract IOP-induced 3D strains. Octant-wise LC strains were also extracted to study the pattern of local deformation. Results: The average LC strain in OHT subjects (3.96%) was significantly lower than that measured in healthy subjects (6.81%; P < 0.05). On average, POAG subjects experienced higher strain than the PACG subjects (4.05%), healthy subjects experienced higher strains than the POAG and PACG subjects, but these difference were not statistically significant. Local LC deformations showed lowest strain in the infero-temporal and temporal octant in the POAG and OHT subjects. Conclusions: We demonstrate measurable LC strains in vivo in humans as a response to acute IOP elevation. In this population, our data suggest that OHT LCs experience lower IOP-induced strains than healthy LCs.

24 Article Inter-relationship between ocular perfusion pressure, blood pressure, intraocular pressure profiles and primary open-angle glaucoma: the Singapore Epidemiology of Eye Diseases study. 2018

Tham, Yih-Chung / Lim, Sing-Hui / Gupta, Preeti / Aung, Tin / Wong, Tien Y / Cheng, Ching-Yu. ·Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore. · Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. · Duke-NUS Medical School, Singapore. · National University Health System, Singapore, Singapore. ·Br J Ophthalmol · Pubmed #29331952.

ABSTRACT: OBJECTIVE: To elucidate the inter-relationship between ocular perfusion pressure (OPP), blood pressure (BP), intraocular pressure (IOP) profiles and primary open-angle glaucoma (POAG) in a multiethnic Asian population. METHODS: Participants were recruited from the Singapore Epidemiology of Eye Diseases Study and underwent standardised ocular and systemic examinations. POAG was defined according to the International Society for Geographical and Epidemiological Ophthalmology criteria. Logistic regression analyses with generalised estimating equation models were performed and used to account for correlation between eyes. RESULTS: A total of 9877 participants (19 587 eyes), including 213 POAG cases (293 eyes) were included. Eyes with lowest quartile levels of systolic OPP (SOPP <110 mm Hg) were 1.85 times (95% CI 1.16 to 2.95) likely to have POAG, compared with eyes with mid-range SOPP levels (123-137 mm Hg; third quartile), after adjusting for relevant covariates and IOP. Consistently, we found that lowest quartile of systolic BP (SBP <124 mm Hg) was 1.69 times (95% CI 1.08 to 2.66) likely to have POAG, compared with mid-range SBP levels (138-153 mm Hg; third quartile). Furthermore, the effect of lower SBP on POAG was more pronounced in eyes with IOP ≥21 mm Hg (OR 3.90; 95% CI 1.24 to 12.30). Both the mean and diastolic profiles of OPP and BP were not significantly associated with POAG, after adjusting for relevant covariates and IOP. CONCLUSIONS: In this population-based sample of nearly 10 000 Asian individuals, we showed that low SOPP was associated with POAG. This association was potentially in part secondary to low SBP and high IOP. Our findings provide further clarity on the roles of OPP surrogates and BP profiles in POAG.

25 Article A Deep Learning Approach to Digitally Stain Optical Coherence Tomography Images of the Optic Nerve Head. 2018

Devalla, Sripad Krishna / Chin, Khai Sing / Mari, Jean-Martial / Tun, Tin A / Strouthidis, Nicholas G / Aung, Tin / Thiéry, Alexandre H / Girard, Michaël J A. ·Ophthalmic Engineering and Innovation Laboratory, Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore, Singapore. · Department of Statistics and Applied Probability, National University of Singapore, Singapore. · GePaSud, Université de la Polynésie Française, Tahiti, French Polynesia. · Singapore Eye Research Institute, Singapore National Eye Centre, Singapore. · NIHR Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, United Kingdom. · Discipline of Clinical Ophthalmology and Eye Health, University of Sydney, Sydney, New South Wales, Australia. · Yong Loo Lin School of Medicine, National University of Singapore, Singapore. ·Invest Ophthalmol Vis Sci · Pubmed #29313052.

ABSTRACT: Purpose: To develop a deep learning approach to digitally stain optical coherence tomography (OCT) images of the optic nerve head (ONH). Methods: A horizontal B-scan was acquired through the center of the ONH using OCT (Spectralis) for one eye of each of 100 subjects (40 healthy and 60 glaucoma). All images were enhanced using adaptive compensation. A custom deep learning network was then designed and trained with the compensated images to digitally stain (i.e., highlight) six tissue layers of the ONH. The accuracy of our algorithm was assessed (against manual segmentations) using the dice coefficient, sensitivity, specificity, intersection over union (IU), and accuracy. We studied the effect of compensation, number of training images, and performance comparison between glaucoma and healthy subjects. Results: For images it had not yet assessed, our algorithm was able to digitally stain the retinal nerve fiber layer + prelamina, the RPE, all other retinal layers, the choroid, and the peripapillary sclera and lamina cribrosa. For all tissues, the dice coefficient, sensitivity, specificity, IU, and accuracy (mean) were 0.84 ± 0.03, 0.92 ± 0.03, 0.99 ± 0.00, 0.89 ± 0.03, and 0.94 ± 0.02, respectively. Our algorithm performed significantly better when compensated images were used for training (P < 0.001). Besides offering a good reliability, digital staining also performed well on OCT images of both glaucoma and healthy individuals. Conclusions: Our deep learning algorithm can simultaneously stain the neural and connective tissues of the ONH, offering a framework to automatically measure multiple key structural parameters of the ONH that may be critical to improve glaucoma management.

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