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The University of Southampton
Medicine

Professor Andrew Lotery MD, FRCOphth

Professor of Ophthalmology, Director, Clinical Neurosciences Research Group, Clinical and Experimental Sciences, Faculty of Medicine,Honorary Consultant Ophthalmologist, University Hospital Southampton NHS Foundation Trust,Research Director for Gift of Sight Appeal (www.giftofsight.org.uk)

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Professor Andrew Lotery is Professor of Ophthalmology within Medicine at the University of Southampton. As a clinician scientist his research is driven by interactions with patients. He works from bench to bedside using molecular genetics and cell biology to study common causes of blindness. His laboratory work is complemented with clinical trials undertaken in Southampton Eye Unit. He is the medical retina lead in Southampton Eye Unit.

Why do people go blind and how can we prevent this? Eye clinics are the busiest they’ve ever been

My focus is creating therapies for retinal diseases such as age related macular degeneration (AMD), the commonest cause of blindness in the developed world . My impact is recognised by two NIHR senior investigator awards, grant funding since 2015 of £12 million, including being the first ophthalmologist to be awarded a £4 million Wellcome Trust Collaborative grant for research into artificial intelligence in Age-related Macular Degeneration (AMD). As an academic founder of Gyroscope Therapeutics in 2019 I led a multicentre UK study identifying dry AMD patients most amenable to gene therapy. In a world first, patients from this study then had gene therapy. I also led the first adequately powered placebo controlled clinical trial for central serous chorioretinopathy (CSR) across 22 UK hospitals. Funded by MRC EME and published in the Lancet in 2020, this study has changed practice worldwide in treating CSR. My markers of esteem include being listed by The Times in their 2010 Top 100 Doctors list. I received the Royal College of Ophthalmologists (RCOphth) Nettleship medal in 2009 for the best research paper published by a British Ophthalmolgist in the previous 4 years. Other awards include the 2012 special award for excellence from the Macular Disease Society; the University Hospital Southampton 2014 Innovation Award and their 2017 Clinical impact via research award. I have served as a clinical expert to National Institute for Heath and Care Excellence (NICE) technology appraisal panels that has resulted in major changes in management of AMD and vitreo-macular traction. I acted as an expert witness for NHS commissioners in a Judicial Review which resulted in the drug bevacizumab being made legal for use in the NHS: potentially saving the NHS £0.5 billion p.a. in AMD drug costs. I serve on the Wellcome Trust Cellular and Molecular Neuroscience Expert Review Group. As Chair of the RCOphth scientific committee I have introduced national policy changes including introducing hydroxychloroquine retinal screening nationally.

 

Research interests

Andrew is interested in understanding the molecular basis of ophthalmic diseases. His University laboratory identifies genetic determinants of eye disease and studies defined mutations in patient derived induced pluripotent stem cells. New therapeutic approaches are also being explored such as gene therapy and retinal cell transplantation. He also leads a dynamic clinical trials team which has participated in many landmark clinical trials developing new treatments for both common conditions such as age related macular degeneration and also rare conditions such as choroideremia. None of this would be possible without the financial support of the Gift of Sight Appeal.

Qualifications

MB BCh BAO, Medicine, Queen’s University, Belfast (1989)
FRCOphth, Ophthalmology, Royal College of Ophthalmology (1994)
MD, Molecular genetics, Queen’s University, Belfast (1997)

Appointments held

2002 - present Professor of Ophthalmology, University of Southampton

2000 – 2002 Assistant Professor of Ophthalmology, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA

1998 – 2000 Fellow in medical retina and molecular ophthalmology, University of Iowa Hospitals and Clinics, USA

1996 – 1998 Specialist Registrar in Ophthalmology, Royal Victoria Hospital, Belfast

1995 – 1996 Research Registrar (Ophthalmology and Medical Genetics), Belfast City Hospital

Research interests

Genetic studies and gene therapy trials

My MD research in Belfast successfully mapped a gene for Central Areolar Choroidal Dystrophy. At the University of Iowa I was part of the team which identified that mutation in Fibulin 3 is the genetic cause of Doyne’s Disease. This led to a simple test for this disease which is now freely available on the NHS and so allows rapid diagnosis and genetic counselling (figure 1).

Again as part of a team, I identified one of the commonest genes (CRB1) to cause Leber congenital amaurosis (LCA) and was one of the first to show that gene therapy is feasible in the macula . My work has therefore assisted in the choice of genes and vectors for human ocular gene therapy trials (which have now started). I am a co-investigator on an ocular clinical gene therapy trial on choroideraemia.

My research group in Southampton has identified several additional genetic risk factors for age related macular degeneration (AMD) (figure 2) and we identified the association of SERPING1 with AMD. For this contribution I was awarded the Nettleship Medal by the Royal College of Ophthalmology for the best research paper published by a British Ophthalmologist in the last four years.

As part of the UK multicentre IVAN study I co-ordinated the collection of DNA samples on participants in this trial so that pharmacogenomic evaluations could be made in AMD. My laboratory was one of the first to identify pharmacogenomic associations in AMD.

I am Chief Investigator on a multi-centre genetic study of primary open angle glaucoma (POAG). Glaucoma is a progressive disease of the optic nerve, resulting in gradual but permanent loss to peripheral vision. We have collected approximately 1500 DNA samples so far (figure 2). Together with researchers at the Wessex Regional Genetics Laboratory in Salisbury, I have been able to establish a test for glaucoma, now available on the NHS. Most recently I have been part of multi-national collaborations seeking to identify novel glaucoma genes. This has resulted in a recent discovery which has been published online in Nature Genetics.

My laboratory has also been instrumental in the genetic understanding of a type of childhood Nystagmus where the eyes have involuntary to-and-fro movements. We have established the genetic cause in a large family with congenital infantile nystagmus (CIN), and are currently recruiting for a large paediatric genetics study.

We are also actively genotyping patients with cone dystrophies, glaucoma and retinitis pigmentosa.

Stem Cell studies

I am investigating the use of human iris pigment epithelium derived stem/progenitor cells and also corneal limbal epithelium derived stem cells, as potential cell sources for transplantation. This work aims to isolate stem cells from iris and corneal tissue, and to drive transdifferentiation towards retinal phenotypes including photoreceptor and RPE cells. From both tissues my team has sucessfully derived RPE and photoreceptor like cells. Our work is now focussing on assessing the functionality of these cells. Although we have been sucessful in deriving retinal lineage cell types, the efficiency of this process is relatively low. The next step for this work will therefore be to use viral gene modification with transcription factors, in an attempt to improve the efficiency of retinal specific differentiation.

Manufacture of artificial cell delivery scaffolds

In collaboration with Dr Grossel’s group in chemistry we have manufactured electrospun fibrous scaffolds using a non-biodegradable synthetic acrylic polymer, which is used clinically in the manufacture of intra-ocular lens (figure 3). The electrospun scaffolds mimic the structure of the inner fibrous layers of native Bruchs membrane. In order to improve cell adhesion, the surface of these fibrous scaffolds has been modified to facilitate attachment of extracellular matrix proteins and short cell adhesion motifs.

Using these scaffolds we are currently carrying out in vitro biocompatibility studies. We are assessing cell attachment, proliferation and viability on different types of fibres and also the effect of various surface modifications. We are also characterizing the phenotype and functionality of the cell monolayer formed on the surface of fibrous scaffolds. In collaboration with Dr Aly Hussain from the Institute of Ophthalmology (UCL), we are carrying out investigations to quantify the elasticity and permeability of the artificial fibrous scaffolds, in comparison to human Bruchs membrane.

Clinical Trials

I run a clinical trials group (figure 4) which is involved in a variety of commericial and NHS funded clinical trials. I have participated in over 10 clinical trials for AMD and diabetes. I have been the UK Chief Investigator for two of these studies. In recognition of my efforts in translational clinical trials I was one of the first 100 investigators in the United Kingdom to be made a National Institute of Health Senior Investigator.

I provide a tertiary referral service in medical retinal diseases including diabetic retinopathy, age-related macular degeneration, vascular diseases, hereditary and acquired macular diseases. I run a cataract operating list with an emphasis on training junior ophthalmologists in cataract surgery. I have responsibility for the delivery of photodynamic therapy (PDT) services for AMD in Hampshire and successfully both wrote and implemented the business case for PDT in Hampshire. I run a weekly special teaching session in fluorescein angiography. I have ongoing research programmes in age-related macular degeneration and ophthalmic genetics. I run a monthly ophthalmic genetics clinic with my colleagues in Clinical Genetics. I have established a medical retinal clinical research fellowship. I provide a national lead on AMD treatments in the NHS including submissions to NICE and the Hampshire Clinical Advisory Priorities Group. I have set up an NHS funded anti-VEGF service at Southampton Eye Unit. I have successfully developed a business plan for this which has resulted in the recruitment of two new consultants and additional staff grade doctors and nursing and imaging staff.

Link to Lotery group medline search

Research projects

Deciphering AMD by Deep Phenotyping and Machine Learning: The Pinnacle study

Clinical efficacy and mechanistic evaluation of Eplerenone for central serous chorio-retinopathy – the VICI randomised trial

Electropherogram of mutation which causes Doyne Disease
Figure 1
Retinal appearance of AMD
Figure 2
Stem cells growing on polymers developed for eye delivery
Figure 3
Clinical Trials Group
Figure 4

Department(s)

Clinical and Experimental Sciences

Affiliate Department(s)

Clinical Neuroscience Research group

Postgraduate student supervision

2020 Rebecca Kaye Current PhD student
2016 Thomas Hallam Current PhD Student (Co-supervisor)
2015 Eloise Keeling PhD Graduated 2019 (Co-supervisor)
2015 Luke O’Gorman PhD student Graduated 2019 (Co-supervisor)
2015 Chelsea Norman PhD student Graduated 2020 (Co-supervisor)
2014 Savannah Lynn PhD student Graduated 2019 (Co-supervisor)
2014 Ahmed Salman PhD student Graduated 2019 (Co-supervisor)
2013 Paul Ibbett PhD student Graduated 2017 (Co-supervisor)
2012 Gareth Ward PhD student Graduated 2016
2008 Xiaoli Chen PhD student Graduated 2012
2008 Sam Khandhadia MBBS MRCOphth PhD Graduated 2013
2005 James Self MRCOphth PhD student Graduated 2009
2005 Neda Bogari PhD student Graduated 2007
2003 Srinivas Goverdhan FRCS PhD student Graduated 2008

Other post-graduate supervision:

2020 Elgin Akyol, Academic Clinical Fellow
2019 Adnan Khan, Clinical Lecturer
2018 Rebecca Kaye, Academic Clinical Fellow
2015 Helena Lee, Clinical Lecturer
2014 Alasdair Warwick Academic Foundation Programme student
2013 Philip Alexander DM
2010 Charles Pierce DM
2009 Jocelyn Cherry Academic Clinical Fellow
2006 Aris Konstantopoulos MSc
2001 David Eliason M.D. Doris Duke Fellow

Medical Student Project Supervision:

2018 Ffion Brown MMedSc First class Hons
2017 Ffion Brown BMedSc
2011 Christina Lim MMedSci First class Hons
2009 Jenani Jegatheeswaran 4th year student study in depth
2009 Aruni Makuloluwa 4th year student study in depth
2008 Katherine Beeson Intercalated BSc First Class Hons
2008 Thea Preston 4th year student study in depth
2007 Sebastian Foster 4th year student study in depth
2006 Mahesan Murugavel 4th year student study in depth
2006 Thomas Marks Intercalated Bsc 2.2 Hons
2005 Dildar Hussain 4th year student study in depth
2005 Matthew Cheung 4th year student study in depth
2004 Joy Okotcha Intercalated BSc 2:1 Hons

National and International responsibilities

01/07/2014 - to date. Member, E3 (European Eye Epidemiology) consortium.
01/04/2014 - to date. Clinical Specialty Lead for Ophthalmology, NIHR Clinical Research Network, Wessex.
01/01/2013 - to date. President Southern Ophthalmological Society
01/05/2012 - to date. Member International Glaucoma Genetics Consortium
01/04/2012 - to date. Grant Award Committee British Council for the Prevention of Blindness
01/01/2012 - to date. Chair of the UK Ophthalmology Steering Committee UK Biobank
01/10/2011 - to date. Director of Clinical Neuroscience Research Group University of Southampton
01/07/2010 - to date. Consultant Representative South Central Eye Care Advisory Group
01/06/2010 - to date. Member International AMD Genetics Consortium Phenotyping Committee
01/01/2010 - to date. Panel member, Integrated Academic Training review panel National Institute for Health Research
01/01/2010-01/12/2010 Biomedical Research Guest Panel Member Sir Jules Thorn Charitable Trust
01/01/2010-01/12/2010 Guest Panel Member, MRC–RCOphth clinical training fellowship Medical Research Council
01/01/2010 - to date. Chairman, Scientific Committee National Eye Research Centre, Bristol
01/09/2009 - to date. Chairman, Academic Ophthalmology Committee Royal College of Ophthalmologists (RCOphth)
01/04/2008 - 01/04/2014. Speciality Lead for Ophthalmology for HIOW CLRN Hampshire & IOW Comprehensive Local Research Network
01/04/2008-01/03/2011 Senior Investigator National Institute for Health Research
01/01/2008 - to date. Surgical training committee Wessex Deanery
01/01/2008 - to date. Editor-in-Chief, Eye Nature Publishing Group
01/01/2008 - to date. Honorary Member, Executive Council Royal College of Ophthalmologists (RCOphth)
01/04/2006-01/08/2008 Medical Advisor RNIB
01/04/2006-01/08/2008 Hampshire NHS commission Medical Advisor
01/04/2006-01/08/2008 Wessex Institute for Health Research and Development Medical Advisor
01/04/2006-01/08/2008 Expert Clinical Advisor National Institute of Clinical Excellence
01/01/2006-01/12/2011 Faculty Member Pfizer "Eyecampus" national educational initiative
01/01/2006-01/12/2009 Member, Scientific Committee National Eye Research Centre
01/09/2005-01/10/2008 Member, Panel of Experts Medical Research Council
01/01/2005-01/01/2008 Assistant Editor, Eye Nature Publishing Group
01/01/2005-01/09/2011 Member, Examination Committee Royal College of Ophthalmologists (RCOphth)
01/01/2004 - to date. Research Director Gift of Sight Appeal, University of Southampton
01/01/2004 - to date. Member, Eye Research UK Group Vision 2020
01/01/2003 - to date. Elected Member Macula Society (USA)
01/09/2002 - to date. Chair of Ophthalmology University of Southampton

University of Southampton

  • Director, Clinical Neurosciences Research Group
  • Research Director, Gift of Sight Appeal

Regional, National and International responsibilities

  • Vice President, National Eye Research Centre
  • Chair, Scientific Committee, Royal College of Ophthalmologists
  • Chair. National UK Biobank Eye and Vision Consortium
  • Specialty lead, Wessex NIHR Clinical Research Network
  • Medical retina lead, University Hospital Southampton NHS Foundation Trust
  • Member, Secretary of State for Transport’s Honorary Medical Advisory Panel on driving and visual disorders
  • NIHR Senior Investigator
  • Expert advisor to Macular Society
  • Member NHS Trust Research Strategy group
  • Member Fight for Sight College of Experts Grant Assessment Panel
  • Scientific and Clinical Adviser and Academic Founder, Gyroscope Therapeutics
  • Member, Wellcome Trust Cellular and Molecular Neuroscience Expert Review Group
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Postgraduate Supervisor for PhD/DM/MSc laboratory based projects for both clinical and basic visual science students

Undergraduate Supervisor offering one MMedSci and one Academic Foundation Programme laboratory based vision science project per year. Postgraduate supervisor offering Integrated PhD rotation projects in both the Immunity and Infection and Stem Cell pathways.

Co-ordinator of weekly Retinal teaching program

Professor Andrew Lotery
University of Southampton Southampton General Hospital LD 70 MP 806 Tremona Road Southampton SO16 6YD Tel: +44 (0)23 8120 5049

Room Number: SGH/LD75/MP806

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