The Dye Is Cast

Uveitis is a potentially blinding condition arising from inflammation within the eye, and the diagnosis and monitoring of it is difficult: it can be hard to detect, it is hard to monitor, and it may be hard to differentiate between its different subtypes. These subtypes may look similar at first presentation, but actually represent pathologically distinct diseases that may benefit from different treatment strategies. Traditionally, the diagnosis is based mainly on the clinical appearance as assessed by a clinician viewing the eye through the slit lamp. This provides sufficient resolution for the clinician to see individual inflammatory cells in the anterior chamber and the anterior vitreous cavity of the eye. However, this single cell visualization is not possible for the posterior structures such as the retina or choroid; this is a critical limitation since these are the sites of the most dangerous forms of uveitis. Additionally, although we can see these cells, we can’t identify what type of immune cell they are; this matters because it leads to us “lumping” forms of uveitis together that look superficially similar, but probably represent different disease processes “under the bonnet.” These limitations hold back our ability to detect, monitor, and differentiate these sight-threatening conditions.

Uveitis is a serious condition globally and is implicated in up to a quarter of cases of blindness in some regions (1, 2). There is a real need for tests that can spot uveitis quickly – and the identification of specific types of inflammatory markers is also important. With this in mind, my team is developing diagnostic tools that could help ophthalmologists identify inflammation from uveitis. When it comes to recognizing ocular inflammation​​, our new eye drop aims to move us away from subjective clinical evaluations and toward a definitive diagnosis.

The science!
 

Our method uses a triazole-derivatized near-infrared cyanine (TNC) dye (developed by our collaborator Marc Vendrell at the University of Edinburgh) that only emits fluorescence when taken up into active inflammatory cells, like T-cells, enabling active inflammation to be visualized on widely available clinical imaging equipment. It’s also a method that can visualize inflammation in “real time.”  Excitingly, we were also able to develop the TNC dye as a topical preparation, thus offering the potential of a “diagnostic eye drop” and avoiding injections.

In the future, our diagnostic dye could help clinicians assess the nature, cell type, and location of inflammation. Being able to identify the type and extent of infiltrating cells, along with their distribution within the eye, would dramatically accelerate our understanding of the sight-threatening forms of uveitis. It would also enable faster, more accurate diagnosis, and give us the ability to monitor the disease more closely than ever before.

Our work also provides the basis for exploring the potential application of our TNC-labeling approach to live immunophenotyping to other serious forms of inflammatory eye disease, such as keratitis, scleritis, and other sight-threatening diseases of the ocular surface. So hopefully there is scope for our work to branch out and help more people.

What’s next?
 

This project was a fantastic team effort, and a real testament to the work that can be achieved through collaboration between amazing research teams – in this case, from the University of Birmingham, University of Bristol, and University of Edinburgh. A special thanks also to Chloe Thomas, Alastair Denniston, and Marc Vendrell for their role in this work. But there is more work to be done. Future lab steps include experiments using the TNC dyes in a mouse model of experimental uveitis (3), which will allow us to assess if we can track active inflammation in uveitis – and help us progress towards clinical utility of the diagnostic eye drop. From there, it’s the road to human testing – and taking anything from mice to humans tends to be an interesting journey; I’m sure that the biggest challenges are yet to present themselves! Nevertheless, we are optimistic and looking forward to sharing more exciting results in the future.