Geraint Williams is an NIHR Academic Clinical Lecturer in Ophthalmology. His sub-specialist area is in cornea and external disease, with an interest in ocular surface immunity and infection. He was awarded a Wellcome Trust clinical research fellowship in 2008 and completed his PhD in Immune Regulation of Acquired Ocular Immunobullous Disease in 2012.
Geraint is currently undertaking his advanced subspecialty training opportunity (ASTO) at the Birmingham and Midland Eye Centre. He is combining this role with his clinical lectureship. His current research projects include the development of our understanding of local immune responses in the ocular surface in health and disease and improving the measurement of clinical disease activity and damage.
Geraint is enthusiastic about imparting knowledge of ocular surface disease, reflected in his commitment to publishing in the field of ophthalmology, communicating with scientific audiences at regional, national and international meetings and talking with lay audiences such as at the British Science Festival.
Geraint graduated from the University of Wales College of Medicine (UWCM), Cardiff in 2002, gaining a distinction for his final MB after undertaking a BSc in Medical Genetics in 2001. He completed his basic specialist training in ophthalmology in the Oxford deanery while gaining membership of the Royal College of Ophthalmologists in 2005. He took up a position as a specialist registrar in the West Midlands in 2006 before securing a Wellcome Trust clinical research fellowship in 2008.
He completed his PhD on the Immune Regulation of Acquired Ocular Immunobullous Disease at the University of Birmingham in 2012. Geraint’s work in to blinding ocular surface scarring diseases has been recognised with an Association for Research and Vision in Ophthalmology international travel grant and a Midland Ophthalmological Society centenary meeting junior ophthalmologists prize in 2012. He has also been an invited speaker at the Royal College of Ophthalmologists showcase session and academic ophthalmology & translational research session at their annual congress.
Geraint was appointed as an NIHR Academic Clinical Lecturer in Ophthalmology in 2012. He has commenced his advanced subspecialty training opportunity in cornea and external disease at the Birmingham and Midland Eye Centre and will continue his senior anterior segment training at the Queen Elizabeth Hospital Birmingham and Moorfields Eye Hospital, London from August 2013.
His current research interests include ocular surface immune regulation in health and disease, and the improved measurement of clinical disease activity and damage. These themes include conjunctival leukocyte function in the healthy and ageing conjunctiva, inflammatory responses in ocular immunobullous disease such as Ocular Mucous Membrane Pemphigoid and Stevens Johnson Syndrome and T cell recognition and regulation of infections such as Herpes Simplex Keratitis. Geraint is also pursuing the establishment of nationally agreed clinical parameters for phenotyping ocular surface disease. He is actively involved in teaching medical students and trainee ophthalmologists at the University of Birmingham and the West Midlands Postgraduate Deanery.
Ocular Surface Immune Regulation in Health and Disease,
Improved Measurement of Clinical Disease Activity and Damage
Ocular Surface Immune Regulation in Health and Disease
Geraint has explored the use of rapid, non-invasive ocular surface impression cytology (OSIC) combined with multi-colour flow cytometry to characterise conjunctival leukocytes. This has provided an insight in to immune regulation in health, ageing and ocular surface diseases (OSD). In healthy individuals, CD8αβ+ effector memory, cytotoxic, mucosal-homing T cells, capable of recognising herpetic viruses are the dominant population in the normal conjunctiva. This population is unaltered with age but other populations such as CD4+ T cells, capable of producing IFN- do increase, indicating a potential role in healthy ageing.
During his PhD, Geraint studied a blinding condition called Ocular Mucous Membrane Pemphigoid (OcMMP), an autoimmune immunobullous disease resulting in conjunctival inflammation and corneal scarring. A major challenge in OcMMP is the observation that scarring may take place without typical signs of inflammation, namely conjunctivitis. By using OSIC in a cohort of patients with OcMMP, an elevation in inflammatory neutrophils were observed and this was associated with progression of scarring, even in the clinically non-inflamed eye. It is hoped that this can be translated in to more effective therapeutic intervention by exploring neutrophils as a biomarker of sub-clinical inflammation and their role in the scarring process.
Following his PhD, Geraint is working on determining a better understanding of immune regulation of the ocular surface infections including T cell recognition and regulation of Herpes Simplex Keratitis (HSK). HSK is an important disease as the Herpes Simplex Viruses (HSV) are responsible for ocular disease including recurrent HSK or inflammation of the cornea. This results in blinding complications including diminished corneal sensation, corneal scarring, the formation of abnormal corneal blood vessels and secondary bacterial infection. He is aiming to determine the frequency of peripheral T cells that recognise HSV immunodominant epitopes and whether they differ in those with and without HSK, in the hope of targeting therapy more effectively.
Improved Measurement of Clinical Disease Activity and Damage
Along side his laboratory work in to the immune regulation of the ocular surface, Geraint has an active interest in improving the clinical phenotyping of human ocular disease. He has previously developed and validated a tool to measure the scarring process in cicatrising conjunctivitis such as OcMMP. This tool has been employed to undertake an anthropological study in to the normal anatomy of the conjunctival fornices in Caucasians.
Geraint has helped establish a steering committee of ocular surface experts from around the UK in order to define activity and damage indices in disease. The aim is to undertake a Delphi process among UK anterior segment and corneal specialists to determine clinical parameters of OSD clinical scoring systems by establishing clear distinctions between activity and damage indices, and validating rankings of disease scales in order to standardise clinical scoring systems for use in clinical trials. This builds on the work undertaken during his PhD, where he validated a Clinical Record Form (CRF) for measuring clinical scoring of cicatrising conjunctivitis.
Furthermore, Geraint is working to improve detection and classification of ocular surface infections such as HSK. He is currently evaluating the role of OSIC coupled with PCR analysis of Herpes Simplex Virus in those with clinical evidence of disease. This is being coupled with in vivo confocal microscopy to determine corneal changes including nerve plexus density in HSK as an adjunct to improving monitoring of disease activity.
Williams GP, Denniston AKO, Oswal KS, Tomlins PJ, Barry RJ, Rauz S and Curnow SJ. ‘The dominant human conjunctival epithelial CD8αβ+ T cell population is maintained with age but the number of CD4+ T cells increases’. Age 2012 34(6):1517-1528
Radford C, Rauz S, Williams GP, Saw VP and Dart JKD. ‘Incidence, Presenting Features and Diagnosis of Cicatrising Conjunctivitis in the United Kingdom’. Eye 2012 doi:10.1038/eye.2012.119
Ghauri AJ, Williams GP, Shah S, Murray PI, Rauz S. ‘Post-phacoemulsification Cytomegalovirus Corneal Endotheliitis: Diagnostic and Management Approaches’. JRSM Short Reports 2012 ;3(6):42. Epub 2012 Jun 27
Denniston AKO, Tomlins PJ, Williams GP, Kottoor S, Khan I, Oswal S, Salmon M, Wallace GR, Rauz S, Murray PI and Curnow SJ. ‘Immune privilege is maintained in human uveitis with aqueous humor suppression of dendritic cell function’. IOVS 2012 Jan 12. [Epub ahead of print]
Williams GP, Radford C, Nightingale P, Dart JKD and Rauz S. ‘Referral and Disease Patterns of Ocular Mucous Membrane Pemphigoid Patients at Two Major United Kingdom Tertiary Referral Hospitals’. Eye 2011 Sep;25(9):1207-18.
Williams GP, Saw VP, Saeed T, Evans ST, Cottrell P, Curnow SJ, Nightingale P, Rauz S. ‘Validation of a Fornix Depth Measurer - A Putative Tool for the Assessment of Progressive Cicatrising Conjunctivitis’. British Journal of Ophthalmology 2011 Jun;95(6):842-7.
Denniston AK, Kottoor SH, Khan I, Oswal K, Williams GP, Abbott J, Wallace GR, Salmon M, Rauz S, Murray PI and Curnow SJ. ‘Endogenous cortisol and TGF-beta in human aqueous humour contribute to ocular immune privilege by regulating dendritic cell function’. Journal of Immunology 2010 186(1):305-11
Williams GP, Tsaloumas MD. ‘The use of intracameral phenylephrine in the management of Intra-Operative Floppy Iris Syndrome following Doxazosin’. Eye 2008 Aug;22(8):1094
Williams GP, Pathak-Ray V, Austin M. ‘Social Impact of Visual Impairment’. British Journal of Ophthalmology 2007;91:986
Williams GP, Mudhar HS, Leyland M. ‘Early pathological features of the cornea in Toxic Epidermal Necrolysis’. British Journal of Ophthalmology 2007; 91: 1129-1132
Williams GP, Pathak-Ray V, Austin M, Lloyd AP, Millington IM and Bennett A. 'Quality of life and visual rehabilitation: an observational study of low vision in three general practices in West Glamorgan’. Eye 2007 Apr 21(4):522-527
Ocular Surface (Editors Benitez-del-Castillo JM and Lemp M). Chapter 12: Sjögren’s Syndrome and Related Conditions. Rauz S, Williams GP and Saw VP. JP Medical 2012 (in press)