MICHEL MICHAELIDES. Michel Michaelides October

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1 MICHEL MICHAELIDES Personal Details Date of birth 1 st January 1973 Home address 54 Hayes Grove, East Dulwich, London, SE22 8DF, UK Mobile number GMC number Present Appointment Professor of Ophthalmology, UCL Institute of Ophthalmology, London and Consultant Ophthalmic Surgeon, Moorfields Eye Hospital, London Previous Appointments Clinical Senior Lecturer, UCL Institute of Ophthalmology, London Ocular Genetics and Paediatric Ophthalmology Fellowships Casey Eye Institute, Portland, Oregon, USA Medical Retina Fellowship, Moorfields Eye Hospital, London Specialist Registrar, Moorfields Eye Hospital, London Specialist Registrar, Charing Cross University Hospital, London Specialist Registrar, Moorfields Eye Hospital, London Specialist Registrar, Whipps Cross University Hospital, London Clinical Research Fellow, Institute of Ophthalmology & Moorfields Eye Hospital, Professors A.T. Moore, D.M. Hunt & J.D. Mollon Personal Statement I have been integral to UCL Institute of Ophthalmology s (IOO) and Moorfields Eye Hospital s (MEH) significant on-going contribution to the understanding of inherited retinal degenerative diseases over the last 12 years, in terms of clinical characterisation, genotype-phenotype correlations, structure-function associations, advanced highresolution quantitative retinal imaging, and the underlying molecular genetics both in terms of identification of novel genes and also characterising the mutation spectrum and prevalence in known genes. My focus now is on the development and validation of clinical trial endpoints to accelerate the process of testing novel therapies. I have over 155 peer-reviewed publications and 18 co-authored book chapters relating to retinal disease with 100 publications since 2010; and have established both national (>50 co-authors at UCL) and international collaborations, including with Professors Joe Carroll and Alfredo Dubra (USA) who are world leaders in Adaptive Optics imaging and Professor Richard Weleber (USA) who is a leading developer of advanced visual field analysis. I have 9 on-going ethically approved studies, including a multi-centre international natural history study (ProgStar -01, -02, -03 and -04) and am also actively involved in retinal clinical trials investigating novel and established therapies. My clinical, research and teaching excellence have being rewarded by being a recipient of prestigious personal funding including a UK Department of Heath Clinical Senior Lecturer award (2010) and an FFB Career Development Award (2011). I have established a Deep Phenotyping IRD Group, including an Adaptive Optics Scanning Laser Ophthalmoscope at IOO - the only one of its kind outside of the USA. This is gamechanging - placing us at the cutting-edge of ocular imaging, allowing us to attract further grant funding (see below), enabling us to undertake gene therapy trials aiming to rescue cone photoreceptor cells, and has helped to establish national and international collaborations. This aforementioned body of work has improved advice on prognosis and genetic counselling, identified the underlying molecular genetic basis of multiple isolated and syndromic disorders, shed light on mechanisms of disease, identified potential novel therapeutic targets, and provided data that will be valuable for current and future therapeutic interventions. Michel Michaelides October

2 Other Appointments And Affiliations Clinical Lead for Electrophysiology at Moorfields Eye Hospital Member of the Moorfields Retinal Research Facilitation Group External Examiner for the Investigative Ophthalmology and Vision Sciences MSc course at Manchester University Co-Director of Moorfields Eye Hospital Medical Retina Fellowship Programme Specialised Ophthalmology National Clinical Reference Group Stakeholder Lead of the Medical Retina Local Faculty Group Medical Retina Representative on the Specialist Services Education Committee Clinician-Scientist Representative on the Quality Review Group Deputy to the lead academic representative on the Ophthalmology Specialty Advisory Group Medical Retina and Ophthalmic Genetics Lead on the Specialised Ophthalmology National Clinical Reference Group Fellow, Royal College of Ophthalmologists Member, American Academy of Ophthalmology Member, The Association for Research in Vision and Ophthalmology Member, European Society of Retina Specialists Member, European Paediatric Ophthalmological Society Qualifications 1994 Intercalated BSc Pharmacology, 1st Class (Kings College London) 1997 MB BS (Kings College London) 2001 MRCOphth 2004 MD (University College London) 2008 FRCOphth 2012 FACS Awards and Prizes 1993 Inchley Prize in Pharmacology Medical Research Council Scholarship for Intercalated BSc 1994 Astra Prize for Cardiovascular Pharmacology Zeneca Prize for Best Intercalated Medical Student 1996 Cargill Prize in Ophthalmology Legg Prize in Surgical Pathology 1997 Oram Prize in Cardiology Blair-Bell Prize in Gynaecology Almond Prize in Diseases of Children 2010 International Guest Scholar, American College of Surgeons Department of Health/HEFCE New Blood Senior Lectureship Award 2011 Foundation Fighting Blindness Career Development Award 2013 Elected to The Macula Society Elected to The British Eye Study Group 2014 Elected to The Retina Society Active External Research Grants Foundation Fighting Blindness (USA) (07/11-07/16; $375,000): Career Development Award - Phenotyping and genotyping adults and children with inherited retinal dystrophies to probe relationships between retinal function and structure, in preparation for planned therapeutic interventions (gene- and stem cell-based, and pharmacological): to M Michaelides National Institute for Health Research (06/12-06/17; 1,968,305) Programme Grant for Applied Research: Towards an evidence-based clinical management of visual hallucinations: prevalence, prognosis, impact and pathophysiology. Co-PI. Michel Michaelides October

3 Wellcome Trust ( ; 737,353) Multi-User Equipment Grant: Animal and human high resolution retinal imaging: to RR Ali, ME Cheetham, F Cordiero, J Greenwood, K Matter, M Michaelides, SE Moss, G Rees, AR Webster. Lead PI on Human Imaging. National Eye Institute (NEI) of the National Institutes of Health (NIH) (U01 EY ; 05/15-04/20; $4,400,000) Platform Technologies for Microscopic Retinal Imaging: Development & Translation: to A Dubra and J Carroll (CIs), D Brainard (PI), J Goldberg (PI), M Michaelides (PI), J Morgan (PI), J Rogers (PI) and R Rosen (PI). British Retinitis Pigmentosa Society (RP Fighting Blindness) (08/11-07/16; 747,085): BRPS centre for the development of gene therapy for inherited retinal dystrophies: to RR Ali, J Bainbridge and M Michaelides. National Eye Institute (NEI) of the National Institutes of Health (NIH) (R01EY017607; 09/13-09/17; $312,000): Assessing photoreceptor structure and function: to J Carroll and M Michaelides. Medical Research Council (07/13-06/18; 2,152,639): Clinical trial of gene therapy for the treatment of achromatopsia: to RR Ali, J Bainbridge and M Michaelides. National Institute for Health Research ( ; 200,000) Rare Diseases Translational Research Collaboration: In-depth phenotyping of Stargardt disease: to M Michaelides, AT Moore and AR Webster. Foundation Fighting Blindness (USA) ( ; $1,302,000) Centre Grant: Research Center for the Study of Retinal Degenerative Diseases at UCL Institute of Ophthalmology and Moorfields Eye Hospital: to RR Ali, SS Bhattacharya, AC Bird, FW Fitzke, GE Holder, M Michaelides, AT Moore, AG Robson, AR Webster. RP Fighting Blindness and Fight for Sight ( ; 1,000,000): To the consortium of the Inherited Retinal Disease Groups at Moorfields Eye Hospital/UCL Institute of Ophthalmology, Manchester, Oxford and Leeds, to fund molecular genetic screening and new gene identification in patients with Retinitis Pigmentosa. PIs at Moorfields Eye Hospital / UCL Institute of Ophthalmology are SS Bhattacharya, ME Cheetham, AJ Hardcastle, M Michaelides, V Plagnol and AR Webster. RP Fighting Blindness ( ; 149,989): The Development Of Human ipsc Derived Ex Vivo Models Of Retinal Degeneration: to SS Bhattacharya, P Coffey, M Michaelides, AT Moore, V Plagnol, AR Webster. Macular Society ( ; 168,606): Assessing retinal structure and function longitudinally in Stargardt disease using in-depth advanced phenotyping in preparation for planned therapeutic intervention: to M Michaelides. Bayer Healthcare ( ; 237,750): Prospective non-randomised pilot study to determine the efficacy of Eylea in cystoid macular oedema associated with Retinitis Pigmentosa: to M Michaelides National Institute for Health Research ( ; 200,000) Rare Diseases Translational Research Collaboration: Longitudinal Deep Phenotyping in Cone Dysfunction Syndromes in Preparation for Trials of Novel Therapies: to M Michaelides. Medical Research Council ( ; 2,971,592): Clinical trial of gene therapy for the treatment of Leber congenital amaurosis: to RR Ali, J Bainbridge and M Michaelides. Michel Michaelides October

4 Fight for Sight ( ; 169,992): Assessing photoreceptor structure and function in X- linked RP associated with RPGR mutations using in-depth advanced phenotyping in preparation for planned therapeutic intervention: to M Michaelides. Current Clinical Trials 1. Principal Investigator, Moorfields Eye Hospital. A Phase I/II, Open-Label, Multi-Center, Prospective Study to Determine the Safety and Tolerability of Sub-retinal Transplantation of Human Embryonic Stem Cell Derived Retinal Pigmented Epithelial (MA09-hRPE) Cells in Patients With Stargardt's Macular Dystrophy 2. Principal Investigator, Moorfields Eye Hospital. To Investigate the Efficacy and Safety of Ranibizumab (Lucentis) in Uveitic Macular Oedema 3. Principal Investigator, Moorfields Eye Hospital. A Prospective Clinical Study of the Effects of Retinal Laser by Multi-spot Photocoagulator on Retinal Sensitivity and Driving Eligibility in Patients With Diabetic Retinopathy. Recent Publications I have over 155 peer-reviewed publications since 2001 and 18 book chapters relating to retinal disease. My Google Scholar h-index is 31, i10-index of 82, with 3350 citations in total. 1. Strauss RW, Dubis AM, Cooper RF, Ba-Abbad R, Moore AT, Webster AR, Dubra A, Carroll J, Michaelides M. Retinal Architecture in RGS9- and R9AP-associated Retinal Dysfunction (Bradyopsia). Am J Ophthalmol Sep 2. [Epub ahead of print] 2. Kohl S, Zobor D, Chiang WC, Weisschuh N, Staller J, Menendez IG, Chang S, Beck SC, Garcia Garrido M, Sothilingam V, Seeliger MW, Stanzial F, Benedicenti F, Inzana F, Héon E, Vincent A, Beis J, Strom TM, Rudolph G, Roosing S, Hollander AI, Cremers FP, Lopez I, Ren H, Moore AT, Webster AR, Michaelides M, Koenekoop RK, Zrenner E, Kaufman RJ, Tsang SH, Wissinger B, Lin JH. Mutations in the unfolded protein response regulator ATF6 cause the cone dysfunction disorder achromatopsia. Nat Genet. 2015;47(7): Bainbridge JW, Mehat MS, Sundaram V, Robbie SJ, Barker SE, Ripamonti C, Georgiadis A, Mowat FM, Beattie SG, Gardner PJ, Feathers KL, Luong VA, Yzer S, Balaggan K, Viswanathan A, de Ravel TJ, Casteels I, Holder GE, Tyler N, Fitzke FW, Weleber RG, Nardini M, Moore AT, Thompson DA, Petersen-Jones SM, Michaelides M, van den Born LI, Stockman A, Smith AJ, Rubin G, Ali RR. Long-term effect of gene therapy on Leber's congenital amaurosis. N Engl J Med. 2015;372(20): Aboshiha J, Dubis AM, Carroll J, Hardcastle AJ, Michaelides M. The cone dysfunction syndromes. Br J Ophthalmol Mar 13. [Epub ahead of print]. 5. Abozaid MA, Langlo CS, Dubis AM, Michaelides M, Tarima S, Carroll J. Reliability and Repeatability of Cone Density Measurements in Patients with Congenital Achromatopsia. Adv Exp Med Biol. 2015;854: Michel Michaelides October

5 6. Aboshiha J, Dubis AM, van der Spuy J, Nishiguchi KM, Cheeseman EW, Ayuso C, Ehrenberg M, Simonelli F, Bainbridge JW, Michaelides M. Preserved Outer Retina in AIPL1 Leber's Congenital Amaurosis: Implications for Gene Therapy. Ophthalmology. 2015;122(4): Fujinami K, Zernant J, Chana RK, Wright GA, Tsunoda K, Ozawa Y, Tsubota K, Robson AG, Holder GE, Allikmets R, Moore AT,* Michaelides M.* Clinical and Molecular Characteristics of Childhood-Onset Stargardt Disease. Ophthalmology. 2015;122(2): Dubis AM, Cooper RF, Aboshiha J, Langlo CS, Sundaram V, Liu B, Collison F, Fishman GA, Moore AT, Webster AR, Dubra A, Carroll J, Michaelides M. Genotype-dependent variability in residual cone structure in achromatopsia: toward developing metrics for assessing cone health. Invest Ophthalmol Vis Sci. 2014;55(11): Aboshiha J, Dubis AM, Cowing J, Fahy RT, Sundaram V, Bainbridge JW, Ali RR, Dubra A, Nardini M, Webster AR, Moore AT, Rubin GS, Carroll J, Michaelides M. A prospective longitudinal study of retinal structure and function in achromatopsia. Invest Ophthalmol Vis Sci. 2014;5(9): Aboshiha J, Luong V, Cowing J, Dubis AM, Bainbridge JW, Ali RR, Webster AR, Moore AT, Fitzke F, Michaelides M. Dark-adaptation functions in molecularly confirmed achromatopsia and the implications for assessment in retinal therapy trials. Invest Ophthalmol Vis Sci. 2014;55(10) Gardner JC, Liew G, Quan YH, Ermetal B, Ueyama H, Davidson AE, Schwarz N, Kanuga N, Chana R, Maher ER, Webster AR, Holder GE, Robson AG, Cheetham ME, Liebelt J, Ruddle JB, Moore AT, Michaelides M, * Hardcastle AJ. * Three Different Cone Opsin Gene Array Mutational Mechanisms; Genotype- Phenotype Correlation and Functional Investigation of Cone Opsin Variants. Hum Mutat. 2014;35(11): Sundaram V, Wilde C, Aboshiha J, Cowing J, Han C, Langlo CS, Chana R, Davidson AE, Sergouniotis PI, Bainbridge JW, Ali RR, Dubra A, Rubin G, Webster AR, Moore AT, Nardini M, Carroll J, Michaelides M. Retinal Structure and Function in Achromatopsia: Implications for Gene Therapy. Ophthalmology. 2014;121(1): A comparison of the causes of blindness certifications in England and Wales in working age adults (16-64 years), with Liew G, Bunce C, * Michaelides M. * BMJ Open. 2014;4(2):e Detailed phenotypic and genotypic characterization of bietti crystalline dystrophy. Halford S, Liew G, Mackay DS, Sergouniotis PI, Holt R, Broadgate S, Volpi EV, Ocaka L, Robson AG, Holder GE, Moore AT, Michaelides M, Webster AR. Ophthalmology. 2014;121(6): A Longitudinal Study of Stargardt Disease: Quantitative Assessment of Fundus Autofluorescence, Progression and Genotype Correlations. Fujinami K, Lois N, Mukherjee R, McBain VA, Tsunoda K, Tsubota K, Stone EM, Fitzke FW, Bunce C, Moore AT, Webster AR, Michaelides M. Invest Ophthalmol Vis Sci. 2013; 54(13): Michel Michaelides October

6 Website Since 2008 I have been writing the scientific, medical and research information provided by Retinitis Pigmentosa Fighting Blindness. This is the primary source of information for patients in the UK with inherited retinal disorders and received over 4 million hits in 2012, 2013 and 2014 respectively suggesting it has a far wider audience. I have an on-going commitment to continued updating of this information; with the last major update undertaken of both clinical and research sections in October Peer Review Peer review for journals since 2008 (Eye, British Journal of Ophthalmology, Acta Ophthalmologica, Retina, American Journal of Ophthalmology, Ophthalmology and Investigative Ophthalmology & Visual Science) Peer review for grants since 2010 (The Wellcome Trust, The Medical Research Council, The Guide Dogs for the Blind Association, The Netherlands Organisation for Health Research and Development Rare Diseases Programme, The Ophthalmic Research Institute of Australia, Foundation Fighting Blindness (USA), National Eye Research Centre, and Fondazione Roma) Selected Recent Invited Talks Invited Talks (i) American College of Surgeons Annual Congress (2010) (ii) St Thomas Hospital Trends in Ophthalmology meeting (2011) (iii) The Royal Society of Medicine - Diabetic Macular Oedema Symposium (2011) (iv) Retinitis Pigmentosa Fighting Blindness Annual General Meeting Keynote Lecture (2012) (v) The Argentinian Society of Ophthalmology Annual Congress (2012) (vi) Foundation Fighting Blindness (USA) VISIONS 2013 Conference (2013) (vii) The European Society of Retina Specialists Annual Congress (2013) (viii) The Hellenic Ophthalmological Society Annual Congress (2014) (ix) International Society for Eye Research Bienniel Meeting (2014) (x) International Symposium on Hereditary Retinal Dystrophies The Biomedical Network Research Centre for Rare Diseases (CIBERER) (2014) (xi) Cambridge Ophthalmological Symposium (2015) (xii) Royal College of Ophthalmologists Seminar on Imaging, Diagnosis and Management of Retinal Diseases (2015) Invited Participant as a Leading Discussant/Chair in International/National Meetings (i) The Royal College of Ophthalmologists National Congress - Genetic Eye Disease Symposium (2011) (ii) Royal National Institute of Blind People Strategy Meeting for (2012) (iii) Foundation Fighting Blindness Funded International Collaboration - to establish and execute a natural history study for Stargardt Disease in preparation for pharmacological intervention only UK invitee (2012-present) (iv) The Royal College of Ophthalmologists National Congress - Paediatric Retinovascular Disease Symposium (2013) (v) The James Lind Alliance priority setting partnership for research in Inherited Retinal Disease (2013) (vi) The Monaciano Symposium International delegation of leading Inherited Retinal Disease clinicians and scientists to discuss future plans and prospects for developing treatments for inherited retinal degeneration and to establish international consortia (2013) (vii) The Royal College of Ophthalmologists National Congress - Electrophysiology Symposium (2014) (viii) The American Academy of Ophthalmology Inherited Retinal Disease and Paediatric Retina Courses Michel Michaelides October

Cross-Sectional and Longitudinal Assessment of Retinal Sensitivity in Patients With Childhood-Onset Stargardt Disease

Article https://doi.org/10.1167/tvst.7.6.10 Cross-Sectional and Longitudinal Assessment of Retinal Sensitivity in Patients With Childhood-Onset Stargardt Disease Preena Tanna 1,2, *, Michalis Georgiou