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Copyright and Use of This Thesis This Thesis Must Be Used in Accordance with the Provisions of the Copyright Act 1968 COPYRIGHT AND USE OF THIS THESIS This thesis must be used in accordance with the provisions of the Copyright Act 1968. Reproduction of material protected by copyright may be an infringement of copyright and copyright owners may be entitled to take legal action against persons who infringe their copyright. Section 51 (2) of the Copyright Act permits an authorized officer of a university library or archives to provide a copy (by communication or otherwise) of an unpublished thesis kept in the library or archives, to a person who satisfies the authorized officer that he or she requires the reproduction for the purposes of research or study. The Copyright Act grants the creator of a work a number of moral rights, specifically the right of attribution, the right against false attribution and the right of integrity. You may infringe the author’s moral rights if you: - fail to acknowledge the author of this thesis if you quote sections from the work - attribute this thesis to another author - subject this thesis to derogatory treatment which may prejudice the author’s reputation For further information contact the University’s Copyright Service. sydney.edu.au/copyright Clinical Studies into the Causes of Idiopathic Macular Telangiectasia Type 2: Sleep Apnoea and Macular Telangiectasia: The SAMTel Project Martin Lee Submitted to the Faculty of Medicine in fulfillment of the requirements of the degree Masters of Philosophy (Medicine) Department of Clinical Ophthalmology & Eye Health University of Sydney January 2015 Acknowledgements: To my family, especially parents, Anne and Russell, and siblings Alison and Frances, thank you for your unbridled support and endless encouragement to enable me to continue to pursue my educational interests. I would specifically like to thank Nathaniel Marshall from the Sydney Nursing School, University of Sydney and the research staff at the Woolcock Institute for their expertise and guidance in sleep medicine. Finally, to my supervisor, Mark Gillies, I cannot thank you enough for your expertise, guidance, but above all friendship throughout this learning adventure. Without you this and everything I have achieved in my professional career would not be possible. The ResMed Foundation provided support to this project by supplying the use of 4 ApneaLink devices with oxymetry channels and 75 disposable nasal cannulae. I would also like to acknowledge the Busselton Population Medical Research Foundation for their assistance in providing the matched controls for the normative database within this study. i Declaration I declare that the research presented here is my own work, except where due acknowledgment is specified and that this body of work has not been submitted to any other university institution for the award of any other diploma or degree or the institute of higher learning. All research carried out in this study was conducted through the Macular Research Unit at the Save Sight Institute, Grounds of Sydney Eye Hospital, University of Sydney between 2011 and 2014. Martin Lee January 2015 ii Abstract Purpose: To assess the prevalence of Obstructive Sleep Apnoea (OSA) in a population with Macular Telangiectasia Type 2 (MacTel Type 2) and how OSA affects MacTel Type 2 progression. Methods: In this case-control study participants completed a questionnaire which incorporated the Berlin Questionnaire (BQ) and questions regarding anthropometric data and medical history. A subset was sequentially selected to undertake overnight sleep analysis using the ResMed ApneaLink™. Using data acquired from the Busselton Population and Medical Research Foundation participants were case- matched based on age, sex and body mass index (BMI) along with, where possible, the presence of hypertension and diabetes. Results: There were 57 (30 ApneaLink™) MacTel Type 2 and 183 controls, respectively. There was no difference in self-reported sleep disordered breathing outcomes between the cohorts using the BQ (p=0.95). Analysis of key indices from ApneaLink™ recordings found that those with an Apnoea -Hypopnoea Index (AHI) and Oxygen Desaturation Index (ODI) > 5 episodes per hour had a more advanced stage of MacTel Type 2 (AHI p = 0.05, ODI p = 0.03). An analysis of the 2 year MacTel Type 2 disease progression rates showed that those diagnosed with OSA progressed at the same rate as those without OSA. Conclusion: Patients with MacTel Type 2 have a high prevalence of OSA which appears to result in a more advanced form of the disease. iii Table of Contents Acknowledgements: ............................................................................................................................. i Declaration: ........................................................................................................................................... ii Abstract:................................................................................................................................................ iii Glossary of Terms: ............................................................................................................................... 1 Chapter 1: Literature Review ............................................................................................................. 3 1.1 Idiopathic Macular Telangiectasia – MacTel Type 2: ................................................. 4 1.1.1 Background: ..................................................................................................................... 4 1.1.2 Epidemiology: .................................................................................................................. 6 1.1.3 Clinical Features: ............................................................................................................. 7 1.1.4 Imaging and Functional Studies: ................................................................................ 11 1.1.4.1 National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) .................. 11 1.1.4.2 Visual Acuity ................................................................................................................. 12 1.1.4.3 Fluorescein Angiography ............................................................................................. 13 1.1.4.4 Microperimetry.............................................................................................................. 13 1.1.4.5 Optical Coherence Tomography (Features of MacTel Type 2) ............................... 14 1.1.4.6 Fundus Autofluorescence Imaging ............................................................................ 17 1.1.5 Treatment ....................................................................................................................... 18 1.1.5.1 Nonproliferative Stage ................................................................................................. 18 1.1.5.1.1 Argon Laser Photocoagulation .................................................................................... 18 1.1.5.1.2 Intravitreal Triamcinolone Acetate ............................................................................. 19 1.1.5.1.3 Vascular Endothelial Growth Factor Inhibitors ........................................................ 20 1.1.5.2 Proliferative Stage ......................................................................................................... 21 1.1.5.2.1 Photodynamic Therapy ................................................................................................ 21 1.1.5.2.2 Intravitreal VEGF Inhibitors ........................................................................................ 22 1.2 Obstructive Sleep Apnoea ........................................................................................... 23 1.2.1 Background: .................................................................................................................. 23 1.2.2 Pathophsyiology ............................................................................................................ 25 1.2.3 Epidemiology ................................................................................................................. 26 1.2.4 Screening Questionnaires............................................................................................. 27 1.2.4.1 Berlin Questionnaire ..................................................................................................... 27 1.2.4.2 Epworth Sleepiness Scale ............................................................................................. 29 1.2.4.3 ResMed ApneaLink™ .................................................................................................. 30 1.2.5 Association with Retinal Disease ................................................................................ 31 1.2.5.1 Central Retinal Vein Occlusion ................................................................................... 31 iv 1.2.5.2 Central Serous Chorioretinopathy .................................................................................. 33 1.2.5.3 Diabetic Macular Oedema ............................................................................................... 33 1.2.6 Treatment ............................................................................................................................ 34 1.3 Müller Cells ........................................................................................................................ 36 1.3.1 Changes in MacTel Type 2 ..............................................................................................
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