The ambition of the MERLIN project is to improve in-depth diagnosis and therapeutic follow-up of diseases that impact the eye’s retina. To do so, the MERLIN partners will deliver a novel medical imaging device able to detect pathological alterations in the retina with highly enhanced sensitivity and specificity. The medical applications of this device encompass a wide range of retinal pathologies, including age-related macular degeneration (AMD), as well as chronic vascular conditions, including diabetes. AMD and diabetic retinopathy (DR) are the leading cause of blindness worldwide in people over 55 years of age. Such diseases slowly develop at the microscopic scale in the retina. Using current imaging techniques, it is difficult to detect them at early stage, and it often takes months to assess the effects of treatments. These limitations hinders both the clinical management of patients and the investigation of new therapies. In order to overcome these issues, the device developed in MERLIN will for the first time enable doctors to examine the retina with multiple imaging modalities at both the macroscopic and microscopic scales. Modalities will include ultrafast scanning laser ophthalmoscopy (SLO), optical coherence tomography (OCT) and OCT angiography (OCT-A), while ultrahigh resolution will be provided by adaptive optics technology. This unique combination will reveal previously invisible cellular and microvascular retinal detail in 3 dimensions. The project partners will also develop advanced image processing software for the visualization and quantitative analysis of microscopic structures, and conduct experimentations to optimize and validate performance in AMD and DR patients. As the feasibility of this diagnostic approach has previously been demonstrated in another European R&D project (FP7 FAMOS, 2012-2017), MERLIN will translate the technology from a preexisting laboratory prototype to a nearly commercial device usable in clinical trials.

Diseases affecting small vessels (less than 150µm diameter) are important causes of morbidity and mortality from cardiovascular and cerebrovascular causes, alone or in association with diseases of large arteries. Predictive biomarkers are obtained from vascular imaging for large vessels. Research on these biomarkers has increased considerably in recent years, because they are more predictive of cardiovascular events than traditional risk factors such as blood pressure. However, at present, these biomarkers are mainly dedicated to the study of large arteries (carotid, aorta). There is indeed no procedure allowing quantitative imaging of small vessels which had proved its interest in the care of patients, due to limitations of imaging technology at this scale. The issue is nevertheless important because high blood pressure and diabetes mainly affects small vessels. In recent years, adaptive optics (AO) imaging of the retina has demonstrated its ability to document retinal structures at the micrometer scale in humans. This technology has now reached sufficient technical maturity to enter clinical routine in a short delay. In continuation of a multidisciplinary collaborative project involving ophthalmologists, engineers, researchers and the manufacturer of an AO camera (the iPhot project, funded by ANR TecSan 2009), we incidentally observed that the latest version of the prototype allowed to document the structure of small arteries, so far inaccessible by other imaging methods. This opens the possibility to develop one or more quantitative biomarkers of the microcirculation. The objective of the ReVeal project is to make vascular imaging by AO simple, efficient and medically useful. For this, we will aim at validating technically and medically new biomarkers measured from small vessel images of OA, in an integrated approach combining an interactive technological developments and medical evaluation. This industrial development project includes four workpackages to be undertaken in parallel: 1- transverse and longitudinal evaluation of vascular imaging in controls and well characterized patients through a multidisciplinary medical network (Head: Clinical Investigation Center 503); 2-implementation of new technology solutions dedicated to vascular imaging (responsible: Imagine Eyes, with Onera-DOTA) 3-Development of software for image processing (co-leaders: Onera-DTIM and L2TI), and 4 - Development of software for data analysis (co-leaders: Telecom ParisTech and ISEP). Eventually it is expected that vascular imaging by OA will play a pivotal role in assessing and monitoring treatment against hypertension and diabetes.

The RetinArt project addresses a major public health issue: cardiovascular (CV) events, which are the leading cause of death in the world. The overall project objective is to validate the arteriolar wall-to-lumen ratio (AWLR), a clinical biomarker of the alterations caused by arterial hypertension (AHT) in small arteries. The clinical validation is expected to prove that assessments of the AWLR enable earlier detection of damage caused by AHT, better prediction of CV risk, and more effective adaptation of AHT therapy to patient. To measure the AWLR biomarker, Imagine Eyes has developed a new retinal imaging system that uses the eye as a window to the microcirculatory system. This instrumentation provides unparalleled microscopic resolution thanks to a breakthrough adaptive optics technology derived from astrophysics. It enables clinicians, for the first time, to directly visualize the microscopic walls of retinal arterioles and quantify the AWLR using automated segmentation software. The examination procedure is totally non invasive and its reliability has been successfully tested with AHT patients in a hospital environment. The phase 1 of the RetinArt project is a feasibility study that aims at establishing the methodological and economic validity of the proposed clinical validation, and at planning its future execution. The main deliverables expected from phase 1 are a validation plan and a detailed business plan. These outcomes are essential milestones in the translation of Imagine Eyes technology to a new standard that will help reduce the risk of serious complications in wide numbers of AHT patients.