Spectroscopic identification of corneal infection

Lead Research Organisation: University of Leicester
Department Name: Physics and Astronomy

Abstract

Using an adaptation of instrumentation originally developed for astronomy using the Faulkes Telescope Spectrometers, this twelve month programme is targeted at the demonstration of a low-cost, non-invasive method of identifying infections in the eye, and specifically, conditions affecting the cornea. This would permit early detection of infections which can lead to rapid and profound loss of vision, and allow accurate targeting of treatment through the unambiguous identification of the nature of the infection. The project includes instrumentation development, laboratory and clinical trials, and the pursuit of a detailed commercialisation plan which includes the identification of potential manufacturers and licensing partners.


Infections of the cornea in the eye can lead to profound loss of vision and in some cases complete destruction of the cornea within 24-48 hours. It is most common in soft contact lens wearers with an incidence of approximately 1 in 10,000 per year. Infections may be caused by bacteria of various types, fungi, viruses and amoebae. Identification of the responsible organism is crucial to selection of appropriate treatment, but techniques have progressed little since those developed by Pasteur and earlier workers in the 18th and 19th century; samples are taken from the infected area and attempts made to culture the organism in laboratories where growth rates vary: it may be several days before organisms can be identified, while the infection grows much more rapidly in the eye. In addition, only in about 50% of cases can laboratory tests identify any growth at all.

Certain bacteria are known to emit fluorescent light when illuminated with an ultraviolet light. Our project aims to characterise the fluorescence from bacteria known to cause problems in the eye, using laboratory-grown cultures. We will then install a source of UV light, together with focusing optics and a fibre optic, onto a spectrometer suitable for installation in slit lamp as found in a hospital ophthalmology department, and use this system to detect the tell-tale fluorescent signature, first in a laboratory, and then (subject to medical ethics committee approval) in a limited series of trials in a hospital, and demonstrate the ability of the system to quickly and reliably detect certain types of eye infection. This device, if proven, could offer the potential to save the sight of hundreds of people each year by allowing treatment decisions to be made more quickly than has been possible to date.

Publications

10 25 50
 
Description The detailed analysis of the spectrum of light from the body can yield information relevant to the diagnosis of a number of serious conditions including scleritis, infection, and cancer. We are developing instrumentation which exploits this fact, to provide rapid identification of the causes of infection, or the presence of cancerous or pre-cancerous tissue. Advantages of the technique are that it is fast (minutes, rather than days for laboratory culture plate tests), minimally invasive, and can be used to access parts of the body which are very challenging to access otherwise (e.g. the back of the eye).

In 2015/16 we showed that our technique is effective at distinguishing one of the major causes of corneal ulcers (acanthamoeba) from other known causes which are difficult to distinguish. This was the subject of a paper, and is leading to further developments in our expanding collaboration.
Exploitation Route Use as a rapid tool for identification of microbial strains in the laboratory. Potential medical instrumentation including implementation in bronchoscopes and hospital slit lamps (for inspection of the eye). Potential licensing of instrumentation for commercial production.
Sectors Agriculture, Food and Drink,Environment,Healthcare,Manufacturing, including Industrial Biotechology

 
Description The outputs from this work have shown that high resolution spectroscopy can provide information that is useful for the diagnosis of conditions affecting the eye, and that measurements on patients are practical with the technology in a hospital environment. Initial work from the research led to a peer-reviewed paper, and the project has now expanded to include fluorescence spectroscopy. This work has been used to file a patent application relating to the in-vivo application of the technology, and has been identified as a promising technology for use in a broader range of clinical targets (including not just the eye but the lungs, skin and other regions). Ex-Vivo tests of the autofluorescence technique have been carried out on freshly resected lung tissue and skin melanomas with encouraging results, and work on this area continues.
First Year Of Impact 2009
Sector Healthcare
Impact Types Societal

 
Description East Midlands Development Agency
Amount £16,000 (GBP)
Funding ID HIRF 493 
Organisation East Midlands Development Agency 
Sector Public
Country United Kingdom
Start 03/2011 
End 01/2012
 
Description Mini Innovation Partnership Scheme
Amount £30,912 (GBP)
Funding ID ST/K003054/1 
Organisation Science and Technologies Facilities Council (STFC) 
Sector Academic/University
Country United Kingdom
Start 08/2012 
End 07/2013
 
Description Dr John LeQuesne - MRC 
Organisation University of Leicester
Department MRC Toxicology Unit
Country United Kingdom 
Sector Public 
PI Contribution We are introducing concepts for potentially powerful new diagnostic capabilities for the detection and diagnosis of cancers in the respiratory system.
Collaborator Contribution The MRC collaboration provides us with clinical expertise in lung cancer and diagnostic/treatment methods and is significant in helping us to establish the key requirements for a diagnostic system based around our technology. It has also provided us with access to hospital laboratory facilities and resected tissue, which is being used to test the instrumentation and method.
Impact Outputs are currently a set of clinical data from hospital laboratory (ex-vivo) trials of our technology. Analysis of the data is in an advanced state and a publication is in preparation.
Start Year 2012
 
Description Dr Simon Kilvington: Microbiology 
Organisation University of Leicester
Country United Kingdom 
Sector Academic/University 
PI Contribution By placing our instrumentation in the microbiology laboratory, the project is providing the opportunity to evaluate the usefulness of high resolution fluorescence spectrometry in the characterisation of microbiological specimens that are responsible for infection, and more generally, to assess the value of the technique in the microbiology laboratory.
Collaborator Contribution Our early work has shown that the instrumentation and technique is capable of identifying a range of distinct spectral signatures in blood agar plate samples. The involvement of Dr Kilvington is critical in enabling the project to demonstrate the reproducible identification of a wide range of clinically significant microorganisms, through an initial survey phase followed by a series of double-blind trials, and is the key step needed to take the concept through to clinical trial stage.
Impact The collaboration is at an early stage with the first cultures currently being grown; the first spectroscopic results are expected within the next 4 weeks.
Start Year 2014
 
Description Dr Wayne Heaselgrave 
Organisation University of Wolverhampton
Department History
Country United Kingdom 
Sector Academic/University 
PI Contribution Introduction of new measurement technique for use in existing research programme.
Collaborator Contribution Dr Heaselgrave brings expertise in microbiology and contacts in the commercial healthcare sector, including companies involved in the production of healthcare products. Dr Heaselgrave's expertise is providing our project with new biological target specimens for analysis, and new applications for the spectroscopic techniques which we are developing. His background is complementary to that of the existing team, and this is opening up new avenues for funding applications, one of which is currently pending a decision.
Impact No outputs yet.
Start Year 2016
 
Description Mr Jeremy Prydal: Ophthalmology 
Organisation University Hospitals of Leicester NHS Trust
Country United Kingdom 
Sector Public 
PI Contribution Provision of expertise in the application of spectroscopic techniques in ophthalmology and other medical fields. Instrument design and data analysis techniques.
Collaborator Contribution Clinical leadership in the development of instrumentation for medical applications. Access to equipment in hospital laboratories and consulting rooms and provision of portable equipment for use in our own laboratories.
Impact Research paper on Scleritis (Bannister, Prydal et al). IP filing. Funding beyond the initial grant period covered by the EPSRC award.
Start Year 2009
 
Title High Resolution Autofluorescence Analysis 
Description High resolution excitation wavelength-resolved autofluorescence spectroscopy for identifying the signatures of infection or cancerous/pre-cancerous tissue in vivo. 
Type Diagnostic Tool - Non-Imaging
Current Stage Of Development Initial development
Year Development Stage Completed 2014
Development Status Under active development/distribution
Impact Potential use as a laboratory analysis tool. 
 
Description Leicester Royal Infirmary Annual Research Presentation Day 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Paper Presentation
Geographic Reach Local
Primary Audience Health professionals
Results and Impact Two talks given on scleritis and microbial infection detection to an audience of ~ 30 consultants, ophthalmologists, trainees and research scientists.

General interest in the technique, good questions but no specific impacts to list.
Year(s) Of Engagement Activity 2013
 
Description MCLOSA 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Paper Presentation
Geographic Reach International
Primary Audience Health professionals
Results and Impact Talk and poster presentation given. An audience of ~150 Consultant Ophthalmologists and Trainees attended the talk and poster presentation, with question session afterwards.

The contribution was shortlisted for the Anthony Bron Award on the basis of the submitted abstract and digital poster. This prize is awarded for the best piece of individually generated UK clinical/basic sciences research by a Clinical Research Fellow or Ophthalmology Trainee working in the area of ocular surface disease. The submission did not win, but was ranked in the top three.
Year(s) Of Engagement Activity 2013
URL http://www.mclosa.org.uk
 
Description Nottingham Eye Symposium 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Paper Presentation
Geographic Reach National
Primary Audience Health professionals
Results and Impact The Nottingham Eye Symposium is an opportunity for the dissemination and discussion of cutting-edge basic science and clinical ophthalmic research. An audience of approximately 120 Consultant Ophthalmologists and trainees listened to the talk.

The talk was well received. A conversation took place after the presentation, with a senior consultant from University of Sheffield. The clinician expressed the view that the work had potential and should be pushed forward. This individual may be a potential future collaborator for work on ocular tumour detection based on the technique.
Year(s) Of Engagement Activity 2013
URL http://www.nottingham.ac.uk/conference/fac-mhs/medicine/nottingham-eye-symposium-and-research-meetin...