Alastair Denniston is Hon Senior Lecturer, College of Medical and Dental Sciences and Consultant Ophthalmologist (Uveitis and Medical Retina) at the University Hospitals Birmingham NHS Foundation Trust.
Alastair’s specialist interests within ophthalmology are ocular immunity, ocular imaging and outcome measurement in inflammatory eye disease. He was awarded an MRC Clinical Research Training Fellowship in 2006, and completed his PhD in Dendritic Cell Regulation in the Ocular Microenvironment in 2009. His laboratory work in immunology is directed towards understanding what causes intraocular inflammation (uveitis) and other forms of inflammatory eye disease.
In the clinic with his collaborator Pearse Keane (University College London, UK), he has demonstrated the potential for newer forms of imaging such as Optical Coherence Tomography (OCT) to provide much-needed objective markers for intraocular inflammation (uveitis). With Pearse Keane and colleagues across the UK and US, he has established EQUATOR, an international collaboration of researchers working on ‘Extended OCT-Quantification of Uveitis Activity for Trial Outcomes and Reporting’. He is a passionate advocate of the need to develop better measures for inflammatory eye diseases which are objective and quantifiable to improve the power of clinical trials and inform day-to-day treatment decisions. This work is balanced by a prioritisation of patient reported outcomes (PROs) for ocular inflammatory disease (with his collaborator Prof Mel Calvert, Head of PROs Group University of Birmingham).
He regularly publishes research papers in scientific journals as well as reviews and book chapters, but is best known for writing the Oxford Handbook of Ophthalmology with Professor Philip Murray (Professor of Ophthalmology and Head of the Academic Unit of Ophthalmology, University of Birmingham).
Alastair is keen to promote awareness of ophthalmic research and has been actively involved with the MRC Max Perutz Science Writing Prize, the Big Bang and the British Science Festival.
Alastair’s motivation, whether in research or in the clinic, is to improve our care of patients with potentially blinding ocular disease.
Ocular immunology, Dendritic cells, Aqueous humour, Clinical Trials, Outcome Measures, Core Outcome Sets, Optical Coherence Tomography, EMEDOCT, VITAN, EQUATOR
The goal of Alastair’s research is directed to
1) Uncovering fundamental mechanisms of ocular inflammation
2) Translating these discoveries into novel therapies that will be of real benefit to patients.
3) Identifying reliable measures of disease acitivitiy and damage that can be used to assess treatment response , predict outcome and stratify therapy.
1) Immunity and its regulation in the eye
Specifically he has investigated the immunosuppressive effects of human aqueous humour on cellular function, and how this is altered in intraocular inflammation, proposing that these early events in the adaptive immune response may explain both the vulnerability of some patients to uveitis, and their natural history - why some resolve quickly and others develop a chronic course.
2) Clinical studies in uveitis and other potentially blinding diseases
Alastair is chief investigator on the study Defining Outcome Measures in Ocular Inflammatory Disease (DOMINO-ID), and principal investigator on numerous observational and interventional clinical studies at University Hospitals Birmingham and Co-Investigator with Prof Philip Murray at the Birmingham & Midland Eye Centre.
3) Imaging and other novel outcome measures for inflammatory eye disease
In the clinic with his collaborator Pearse Keane (University College London, UK), Alastair has demonstrated the potential for newer forms of imaging such as Optical Coherence Tomography (OCT) to provide much-needed objective markers for intraocular inflammation (uveitis). He is a passionate advocate of the need to develop better measures for inflammatory eye diseases which are objective and quantifiable. This will significantly improve the power of clinical trials (smaller, faster trials with a higher chance of success) and inform day-to-day treatment decisions. Establishing an international collaboration of researchers working on ‘Extended OCT-Quantification of Uveitis Activity for Trial Outcomes and Reporting’ (EQUATOR) has been a key part of advancing this.
This work is balanced by a prioritisation of patient reported outcomes (PROs) for ocular inflammatory disease (with his collaborator Prof Mel Calvert, Head of PROs Group University of Birmingham). Alastair is also leading on the development of a consensus Core Outcome Set for Uveitis for use across all future trials for patients with uveitis, to reduce research waste and ensure that maximum value can be gathered for each study.
Denniston AK, Keane PA. Paravascular pathways in the eye: is there an 'Ocular Glymphatic System'? IOVS 2015 (In Press)
Keane PA, Balasakas K, Sim DA, Aman K, Denniston AK, Aslam T for the EQUATOR study group. Automated analysis of vitreous inflammation using SD-OCT. TVST. 2015 (in press)
Barry RJ, Denniston AK. Controversies in the pharmacological treatment of uveitis. Current Pharmaceutical Design 2015 (In Press)
Chen P, Denniston A, Hannes S, Tucker W, Wei L, Liu B, Xiao T, Hirani S, Li Z, Jawad S, Si H, Lee RW, Sen HN, Nussenblatt RB. Increased CD1c(+) mDC1 with mature phenotype regulated by TNFα-p38 MAPK in autoimmune ocular inflammatory disease. Clin Immunol. 2015 May;158(1):35-46. doi: 10.1016/j.clim.2015.03.002. Epub 2015 Mar 14. PubMed PMID: 25784146; PubMed Central PMCID: PMC4420697
Chen P, Denniston AK, Hirani S, Hannes S, Nussenblatt RB. Role of dendritic cell sub sets in immunity and their contribution to noninfectious uveitis. Surv Ophthalmol. 2015 May-Jun;60(3):242-249. doi: 10.1016/j.survophthal.2015.01.003. Epub 2015 Jan 28. Review. PubMed PMID: 25749202; PubMed Central PMCID:PMC4404222.
Lane M, Mathewson PA, Sharma HE, Palmer H, Shah P, Nightingale P, Tsaloumas MD,Denniston AK. Social deprivation as a risk factor for late presentation of proliferative diabetic retinopathy. Clin Ophthalmol. 2015 Feb 17;9:347-52. doi: 10.2147/OPTH.S73272. eCollection 2015. PubMed PMID: 25733801; PubMed Central PMCID: PMC4337620.
Mollan SP, Mackie S, O’Sullivan E, Denniston AK. Increase in admissions related to Giant Cell Arteritis and Polymyalgia Rheumatica in the UK, 2002-2013, without a decrease in associated sight loss: potential implications for service provision. Rheumatology 2014 (In press)
Denniston AK, Beales PL, Tomlins P, Good P, Langford M, Foggensteiner L, Williams D, Tsaloumas MD.Evaluation of Visual Function and Needs in Adult Patients with Bardet-Biedl Syndrome. Retina 2014 (In Press)
Barry RJ, Nguyen QD, Lee RW, Murray PI, Denniston AK. Pharmacotherapy for uveitis: current management and emerging therapy. Clin Ophthalmol. 2014; 2014 Sep22;8:1891-911. doi: 10.2147/OPTH.S47778.
Mollan SP, Sharrack N, Burdon MA, Denniston AK. Aspirin as adjunctive treatment for giant cell arteritis. Cochrane Database Syst Rev. 2014 Aug 3;8:CD010453. [Epub ahead of print] PubMed PMID: 25087045.
Sharma HE, Mathewson PA, Lane M, Shah P, Glover N, Palmer H, Haque MS, Denniston AK, Tsaloumas MD. The role of social deprivation in severe neovascular age-related macular degeneration. Br J Ophthalmol. 2014 Jul 4. pii:bjophthalmol-2014-304959. doi: 10.1136/bjophthalmol-2014-304959. [Epub ahead of print] PubMed PMID: 24997180.
Keane PA, Karampelas M, Sim DA, Sadda SR, Tufail A, Sen HN, Nussenblatt RB, Dick AD, Lee RW, Murray PI, Pavesio CE, Denniston AK. Objective Measurement of Vitreous Inflammation Using Optical Coherence Tomography. Ophthalmology. 2014 May 15. pii: S0161-6420(14)00230-9. doi: 10.1016/j.ophtha.2014.03.006. [Epub ahead of print] PubMed PMID: 24835759.
Denniston AK, Kyte D, Calvert M, Burr JM. An introduction to patient-reported outcome measures in ophthalmic research. Eye (Lond). 2014 Jun;2(6):637-45. doi: 10.1038/eye.2014.41. Epub 2014 Mar 14. PubMed PMID: 24625379.
Denniston AK, Dick AD. Systemic therapies for inflammatory eye disease: past, present and future. BMC Ophthalmol. 2013 Apr 24;13:18. doi: 10.1186/1471-2415-13-18. Review. PubMed PMID: 23617902; PubMed Central PMCID: PMC3639939.