Research summary
My work on cytokines including TNF-alpha and the role of microglia in ocular inflammation (and retinal degeneration), has delivered new insights into the pathogenesis and new approaches to treatment of this group of important blinding diseases. I have been instrumental in taking these insights through to novel treatments. In the 90’s I lead the move of biologic therapy for uveitis forward in ophthalmology. Underpinned by experimental data, I first reported in a largest case series use of CAMPATH-1H via his collaboration with John Isaacs and Herman Waldmann for the successful treatment of refractory retinal vasculitis and ocular Wegener’s Granulomatosis (Brit J Ophthalmol 2000: 107-9; Brit J Ophthalmol 1999; 83: 1230). Furthermore my continued bench to bedside approach has been seminal in generating the evidence and scientific rationale that has led to the success of the use of anti-TNF agents in the treatment of non-infectious ocular inflammatory disease enjoyed in clinic today and has led to his many writings of reviews both science and clinical in this area (e.g. Prog Ret Eye Res 2004; 23: 617). With the science backdrop in my lab of basic macrophage biology and translational preclinical work (developed recently seminal paper for preclinical model outcomes utilizing Flow cytometry of single cell analysis alongside robust clinical outcomes non-invasively in animal models (IOVS , 2008: 49: 5458), I have generated evidence of macrophage plasticity during inflammatory and degenerative responses in the retina that has highlighted pathways for biologic therapeutic intervention such as agonist CD200R and C5aR inhibition to lead to early phase trials. In addition, we been one of only a very few groups that have generated via the expansive clinical experience and tertiary regional service in the NHS, evidence via our own RCTs (e.g Arch Ophthalmol 2005; 123: 634) in the use of standard immunosuppressive agents, quality of life (Brit J Ophthalmol 2005; 89: 1161) and ultimately improved care packages for patients.

Our work then set us to be engaged and incorporated and co-applicants of both the 2012 award for the £26.5M Experimental Biomedical Medicine platform of the NIHR-BRC at Moorfields and Institute of Ophthalmology, UCL and the successful UCL-Moorfields £5M Jules Thorn Infrastructural Application. We are now at an unparalleled time and have created consortium (NIH, USA and China) to build links to establish the operational infrastructure and large patient cohorts to deliver better understanding of mechanisms in man, undertake deep phenotyping, establish and test biomarkers, and a population for clinical trials.