Glaucoma Research Group

Overview

Angle-Closure Glaucoma and Glaucoma Genetics Research Group

Prof Aung Tin

My research focuses on angle-closure glaucoma (ACG) and glaucoma genetics. Our work is dedicated to uncovering the mechanisms underlying primary angle-closure glaucoma (PACG), a major form of glaucoma and cause of blindness in Asia, and developing improved strategies for its prevention and treatment. Our research group is currently conducting large-scale studies on the epidemiology, risk factors, imaging, clinical phenotypes, genetics and management of PACG. By utilizing advanced imaging technologies, we aim to identify novel biomarkers and mechanisms that enable earlier detection and more effective interventions. Additionally, we are exploring the genetic contributors to PACG by analyzing extensive datasets from whole exome sequencing, with the goal of discovering critical genes involved in the disease's development.

In the broader field of glaucoma genetics, our group is leading international collaborations to uncover genetic loci associated with various forms of glaucoma, including PACG, exfoliation glaucoma, and open-angle glaucoma. Through extensive genome-wide association studies (GWAS), whole exome sequencing (WES), and partnerships with global consortia, we aim to enhance diagnostic tools, deepen insights into disease mechanisms, and determine the biology of newly discovered gene(s) as potential therapeutic targets with the goal for direct clinical application.

Ocular Imaging Research Group

Prof Leopold Schmetterer

Figure 2. Demonstration of using normative capillary perfusion maps in quantifying capillary defects in glaucoma eyes. A,E) Visual fields. B,F) grayscale 12x12 mm2 OCT angiography images C,G) capillary perfusion maps, D,H) visualisation of the loci and severities of the capillary defects in glaucoma eyes.

We are developing novel imaging devices aimed to improve diagnosis and follow up of glaucoma patients. These devices are based on optical coherence tomography (OCT) and aim to obtain meaningful parameters that are related to the disease processes.

Examples include OCT angiography to visualise the retinal and choroidal capillary network, polarisation-sensitive OCT to measure birefringence of tissue, hyperspectral OCT to detect abnormal scattering and absorption of injured ganglion cells and OCT-based opto-physiology to study intrinsic signals from retinal neurons in response to light stimulation.

In addition, we are interested in structure /function relationship in glaucoma for improved follow up as well as novel analysis technique for OCT images using both multi-regression models and AI-based approaches.

Deep Phenotyping and Genetic Landscaping of Primary Open Angle Glaucoma

Prof Cheng Ching-Yu

We aim to establish a large-scale DNA biobank for primary open angle glaucoma (POAG), linking rich glaucoma functional and structural phenotypic data, to comprehensively characterise the genetic profiles of this disease.

We will achieve this using state-of-the-art ocular imaging and systematic characterisation of low-frequency coding variants underlying POAG through whole-exome sequencing. The discovery of protein-changing mutations will revolutionise the field of glaucoma genetics and may lead to the development of genetic tests for high-risk individuals who will benefit from timely interventions to slow the rate of disease progression of disease or open new avenues for drug targets. This will facilitate precision medicine, tailoring treatment or prevention strategies according to individuals’ unique characteristics.

Neurovascular Dysfunction in Glaucoma

Dr Rachel Chong

Many glaucoma patients continue to suffer sight-loss despite the clinician’s best efforts to lower their intraocular pressure. Recent research points to a close relationship between nerve cells and vascular cells that provide oxygen and nutrients to support important neuronal connections. We aim to understand how the eye regulates blood flow internally despite changes in eye pressure and factors that influence systemic blood pressure. Our lab focuses on real time, dynamic changes that occur in preclinical models of glaucoma through the use of specialised imaging devices. I also have an interest in the relationship between high myopia and glaucoma, and run a dedicated service for this high risk group of patients. We are exploring novel methods of improving the management of this type of glaucoma that frequently poses a diagnostic challenge, through novel approaches to monitoring changes in neuronal and vascular markers in the eye.

Translational Ophthalmic Pathology Research Platform

Dr Anita Chan

Our platform focuses on experimental glaucoma models (Figure 5) and harnesses our pathology expertise to study the ultrastructural changes using electron microscopy (Figure 6) and histological structural changes (Figure 5) that occur because of an increased eye pressure on the optic nerve and retina. We then correlate this with our clinical in vivo imaging so we can translate this to clinical care.

We then study the role of various drugs and interventions to see if we can delay and even prevent these changes and thus the progression of glaucoma. Our experimental glaucoma models include open angle glaucoma as well as a primary angle closure model which allows us to comprehensively study and evaluate novel therapies for the more common types of glaucoma in Singapore and in the world.

Publications

1. Zhao M, Sun Q, Oatts J, Hu G, Ge L, Zhu B, Fu M, Wang Y, Miao Y, Luo Q, Niu T, Yu Y, Ying GS, Aung T, Xu X, Han Y. Changes in Intraocular Pressure and Angle Structure after Dilation in Primary Angle-Closure Suspects with Visually Significant Cataract. Ophthalmology. 2021 Jan;128(1):39-47.
2. Porporato N, Baskaran M, Perera S, Tun TA, Sultana R, Tan M, Quah JH, Allen JC, Friedman D, Cheng CY, Aung T. Evaluation of Meridional Scans for Angle Closure Assessment with Anterior Segment Swept-source Optical Coherence Tomography. Br J Ophthalmol. 2021 Jan;105(1):131-134.
3. Soh ZD, Thakur S, Majithia S, Nongpiur ME, Cheng CY. Iris and its Relevance to Angle Closure Disease: A Review. Br J Ophthalmol. 2021 Jan;105(1):3-8.
4. Bell K, de Padua Soares Bezerra B, Mofokeng M, Montesano G, Nongpiur ME, Marti MV, Lawlor M. Learning from the Past: Mitomycin C Use in Trabeculectomy and its Application in Bleb-forming Minimally Invasive Glaucoma Surgery. Surv Ophthalmol. 2021 Jan-Feb;66(1):109-123.
5. Huang OS, Seet LF, Ho HW, Chu SW, Narayanaswamy A, Perera SA, Husain R, Aung T, Wong TT. Altered Iris Aquaporin Expression and Aqueous Humor Osmolality in Glaucoma. Invest Ophthalmol Vis Sci. 2021 Feb 1;62(2):34.
6. Genetics of Exfoliation Syndrome Partnership, Li Z, Wang Z, Lee MC, Zenkel M, Peh E, Ozaki M, Topouzis F, Nakano S, Chan A, Chen S, Williams SEI, Orr A, Nakano M, Kobakhidze N, Zarnowski T, Popa-Cherecheanu A, Mizoguchi T, Manabe SI, Hayashi K, Kazama S, Inoue K, Mori Y, Miyata K, Sugiyama K, Higashide T, Chihara E, Ideta R, Ishiko S, Yoshida A, Tokumo K, Kiuchi Y, Ohashi T, Sakurai T, Sugimoto T, Chuman H, Aihara M, Inatani M, Mori K, Ikeda Y, Ueno M, Gaston D, Rafuse P, Shuba L, Saunders J, Nicolela M, Chichua G, Tabagari S, Founti P, Sim KS, Meah WY, Soo HM, Chen XY, Chatzikyriakidou A, Keskini C, Pappas T, Anastasopoulos E, Lambropoulos A, Panagiotou ES, Mikropoulos DG, Kosior-Jarecka E, Cheong A, Li Y, Lukasik U, Nongpiur ME, Husain R, Perera SA, Álvarez L, García M, González-Iglesias H, Fernández-Vega Cueto A, Fernández-Vega Cueto L, Martinón-Torres F, Salas A, Oguz Ç, Tamcelik N, Atalay E, Batu B, Irkec M, Aktas D, Kasim B, Astakhov YS, Astakhov SY, Akopov EL, Giessl A, Mardin C, Hellerbrand C, Cooke Bailey JN, Igo RP Jr, Haines JL, Edward DP, Heegaard S, Davila S, Tan P, Kang JH, Pasquale LR, Kruse FE, Reis A, Carmichael TR, Hauser M, Ramsay M, Mossböck G, Yildirim N, Tashiro K, Konstas AGP, Coca-Prados M, Foo JN, Kinoshita S, Sotozono C, Kubota T, Dubina M, Ritch R, Wiggs JL, Pasutto F, Schlötzer-Schrehardt U, Ho YS, Aung T, Tam WL, Khor CC. Association of Rare CYP39A1 Variants With Exfoliation Syndrome Involving the Anterior Chamber of the Eye. JAMA. 2021 Feb 23;325(8):753-764.
7. Gharahkhani P, Jorgenson E, Hysi P, Khawaja AP, Pendergrass S, Han X, Ong JS, Hewitt AW, Segrè AV, Rouhana JM, Hamel AR, Igo RP Jr, Choquet H, Qassim A, Josyula NS, Cooke Bailey JN, Bonnemaijer PWM, Iglesias A, Siggs OM, Young TL, Vitart V, Thiadens AAHJ, Karjalainen J, Uebe S, Melles RB, Nair KS, Luben R, Simcoe M, Amersinghe N, Cree AJ, Hohn R, Poplawski A, Chen LJ, Rong SS, Aung T, Vithana EN, NEIGHBORHOOD consortium, ANZRAG consortium, Biobank Japan project, FinnGen study, UK Biobank Eye and Vision Consortium, GIGA study group, 23 and Me Research Team, Tamiya G, Shiga Y, Yamamoto M, Nakazawa T, Currant H, Birney E, Wang X, Auton A, Lupton MK, Martin NG, Ashaye A, Olawoye O, Williams SE, Akafo S, Ramsay M, Hashimoto K, Kamatani Y, Akiyama M, Momozawa Y, Foster PJ, Khaw PT, Morgan JE, Strouthidis NG, Kraft P, Kang JH, Pang CP, Pasutto F, Mitchell P, Lotery AJ, Palotie A, van Duijn C, Haines JL, Hammond C, Pasquale LR, Klaver CCW, Hauser M, Khor CC, Mackey DA, Kubo M, Cheng CY, Craig JE, MacGregor S, Wiggs JL. Genome-wide Meta-analysis Identifies 127 Open-angle Glaucoma Loci with Consistent Effect Across Ancestries. Nat Commun. 2021 Feb 24;12(1):1258.
8. Tribble JR, Hui F, Jöe M, Bell K, Chrysostomou V, Crowston JG, Williams PA. Targeting Diet and Exercise for Neuroprotection and Neurorecovery in Glaucoma. Cells. 2021 Feb 1;10(2):295.
9. Chong RS, Crowston JG, Wong TT. Experimental models of glaucoma filtration surgery. Acta Ophthalmol. 2021 Feb;99(1):9-15.
10. Cheong H, Krishna Devalla S, Chuangsuwanich T, Tun TA, Wang X, Aung T, Schmetterer L, Buist ML, Boote C, Thiéry AH, Girard MJA. OCT-GAN: Single Step Shadow and Noise Removal from Optical Coherence Tomography Images of the Human Optic Nerve Head. Biomed Opt Express. 2021 Feb 19;12(3):1482-1498.
11. Wong D, Chua J, Baskaran M, Tan B, Yao X, Chan S, Tham YC, Chong R, Aung T, Lamoureux EL, Vithana EN, Cheng CY, Schmetterer L. Factors Affecting the Diagnostic Performance of Circumpapillary Retinal Nerve Fibre Layer Measurement in Glaucoma. Br J Ophthalmol. 2021 Mar;105(3):397-402.
12. Liu C, Nongpiur ME, Cheng CY, Khor CC, Yu M, Husain R, Ho CL, Wong TT, Boey PY, Perera S, Wong TY, Vithana EN, Aung T. Evaluation of Primary Angle-Closure Glaucoma Susceptibility Loci for Estimating Angle Closure Disease Severity. Ophthalmology. 2021 Mar;128(3):403-409.
13. Casson RJ, Chidlow G, Crowston JG, Williams PA, Wood JPM. Retinal Energy Metabolism in Health and Glaucoma. Prog Retin Eye Res. 2021 Mar;81:100881.
14. Chong RS, Chee ML, Tham YC, Majithia S, Thakur S, Teo ZL, Da Soh Z, Chua J, Tan B, Wong DWK, Schmetterer L, Sabanayagam C, Cheng CY. Association of Antihypertensive Medication with Retinal Nerve Fiber Layer and Ganglion Cell-inner Plexiform Layer Thickness. Ophthalmology. 2021 Mar;128(3):393-400.
15. Currant H, Hysi P, Fitzgerald TW, Gharahkhani P, Bonnemaijer PWM, Senabouth A, Hewitt AW; UK Biobank Eye and Vision Consortium; International Glaucoma Genetics Consortium, Atan D, Aung T, Charng J, Choquet H, Craig J, Khaw PT, Klaver CCW, Kubo M, Ong JS, Pasquale LR, Reisman CA, Daniszewski M, Powell JE, Pébay A, Simcoe MJ, Thiadens AAHJ, van Duijn CM, Yazar S, Jorgenson E, MacGregor S, Hammond CJ, Mackey DA, Wiggs JL, Foster PJ, Patel PJ, Birney E, Khawaja AP. Genetic Variation Affects Morphological Retinal Phenotypes Extracted from UK Biobank Optical Coherence Tomography Images. PLoS Genet. 2021 May 12;17(5):e1009497.
16. Tribble JR, Otmani A, Sun S, Ellis SA, Cimaglia G, Vohra R, Jöe M, Lardner E, Venkataraman AP, Domínguez-Vicent A, Kokkali E, Rho S, Jóhannesson G, Burgess RW, Fuerst PG, Brautaset R, Kolko M, Morgan JE, Crowston JG, Votruba M, Williams PA. Nicotinamide Provides Neuroprotection in Glaucoma by Protecting Against Mitochondrial and Metabolic Dysfunction. Redox Biol. 2021 Jul;43:101988.
17. Loo Y, Tun TA, Vithana EN, Perera SA, Husain R, Wong TT, Aung T, Nongpiur ME. Association of Peripheral Anterior Synechiae with Anterior Segment Parameters in Eyes with Primary Angle Closure Glaucoma. Sci Rep. 2021 Jul 6;11(1):13906.
18. Xu BY, Friedman DS, Foster PJ, Jiang Y, Pardeshi AA, Jiang Y, Munoz B, Aung T, He M. Anatomic Changes and Predictors of Angle Widening after Laser Peripheral Iridotomy: The Zhongshan Angle Closure Prevention Trial. Ophthalmology. 2021 Aug;128(8):1161-1168.
19. Fenwick EK, Ozdemir S, Man REK, Baid D, Htoon HM, Gan ATL, Tey ML, Aw AT, Baskaran M, Nongpiur ME, Finkelstein EA, Tey CS, Soon HJT, Sabanayagam C, Sng CCA, Wong TY, Husain R, Perera SA, Lun K, Aung T, Lamoureux EL. Development and Validation of a Preference-based Glaucoma Utility Instrument Using Discrete Choice Experiment. JAMA Ophthalmol. 2021 Aug 1;139(8):866-874.
20. Soh Z, Yu M, Betzler BK, Majithia S, Thakur S, Tham YC, Wong TY, Aung T, Friedman DS, Cheng CY. The Global Extent of Undetected Glaucoma in Adults: A Systematic Review and Meta-analysis. Ophthalmology. 2021 Oct;128(10):1393-1404.
21. He M, Jiang Y, Huang S, Chang DS, Munoz B, Aung T, Foster PJ, Friedman DS. Laser peripheral iridotomy for the prevention of angle closure: a single-centre, randomised controlled trial. Lancet. 2019 Apr 20;393(10181):1609-1618.
22. Genetics of Glaucoma in People of African Descent (GGLAD) Consortium., Hauser MA, Allingham RR, Aung T, et al. Association of Genetic Variants With Primary Open-Angle Glaucoma Among Individuals With African Ancestry. (Joint First Author). JAMA. 2019 Nov 5;322(17):1682-1691.
23. Aung T, Ozaki M, Lee MC …Khor CC. Genetic association study of exfoliation syndrome identifies a protective rare variant at LOXL1 and five new susceptibility loci. Nat Genet. 2017 Jul;49(7):993-1004.
24. Aung T, Ozaki M, …Khor CC A common variant mapping to CACNA1A is associated with susceptibility to Exfoliation syndrome. Nature Genetics 2015 Jun,47(6) 689.
25. Jonas JB, Aung T, Bourne RR, Bron AM, Ritch R, Panda-Jonas S. Glaucoma. Lancet. 2017 Nov 11;390(10108):2183-2193.
26. Khor CC, Do T, Jia H,… Aung T. Genome-wide association study identifies five new susceptibility loci for primary angle closure glaucoma. Nature Genetics 2016 May;48(5):556-62.
27. Hysi PG, Cheng CY, …Aung T. Genome-wide Analysis of Multi-ancestry Cohorts Identifies New Loci Influencing Intraocular Pressure and Susceptibility to Glaucoma. Nat Genet- 2014; 46(10): 1126-30.
28. Weinreb RN, Aung T, Medeiros FA. The Pathophysiology and Treatment of Glaucoma: A Review. JAMA. 2014 May 14;311(18):1901-11.
29. Vithana EN, Khor CC,…Aung T. Genome-wide association analyses identify three new susceptibility loci for Primary Angle Closure Glaucoma. Nat Genetics 2012; 44: 1142-6.

Members

Research Team

Research Optometrists/ Coordinators/ Assistants