FLUOSICCA

Dry eye syndrome (DES) is a worldwide disease that affects the quality of life of millions of individuals to varying degrees. If the positive diagnosis is generally very easy, the objective and reliable determination of its severity (grading) remains the main diagnostic problem for decades. In practice, two very different situations must be distinguished: routine clinical practice where grading is necessary to personalize treatment and clinical trials where grading is essential to demonstrate the efficacy of a new treatment: 1/ In routine clinical practice, the clinician collects the symptoms, observes the ocular surface stained with fluorescein to assess superficial punctate keratitis and tear film break-up time and estimates the quantity of tear using the Schirmer test. 2/ During clinical trials, the very high imprecision and/or the lack of reliability (precision, accuracy, repeatability) of the 3 tests forces the addition of other evaluation criteria, like different biomarkers but none of which has ever been imposed or transferred to routine use. FLUOSICCA aims to revolutionize the diagnosis of the severity and monitoring of dry eye syndrome by developing a process combining fluorescence imaging and biology. We will quantify in situ a pair of biomarkers, directly on the ocular surface of patients in a sensitive and specific manner: a marker of constant or little variation in the pathology and serves to normalize the signal and a marker that is overexpressed in dry eye syndrome. The measurement of a ratio will reduce inter and intra individual variability. The ligands of the two biomarkers (Partner 3) will be synthetic, non-immunogenic, stable and easily customizable proteins. They will be coupled to functionalized BODIPY fluorophores (Partner 2), excitable in a non-dazzling wavelength range (>650 nm, easy to tolerate) while maintaining brightness and photostability. The imaging device (Partner 4) will be sensitive and can be industrialized on a large scale. It will allow the detection and discrimination of the two fluorophores in order to calculate their ratio. The whole system will first be developed in vitro on cells expressing the two biomarkers, then tested on primary ocular epithelial cells and on human corneas preserved in partner 1's bioreactor, using an innovative dry eye ex vivo model. This integrated solution will then be transposable to other biomarkers and other pathologies of the ocular surface.