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European Dry Eye Network

Periodic Reporting for period 2 - EDEN (European Dry Eye Network)

Reporting period: 2017-03-01 to 2019-02-28

The primary objectives of EDEN were:
1. to advance in the understanding of Dry Eye Disease (DED) and provide diagnostic and therapeutic innovations for this most frequent of all ophthalmic diseases
2. to train 10 early-stage researchers (ESRs) in state-of-the-art concepts and research techniques essential to the study of the human eye, while providing them with strong career-management skills and sound professional network
3. to boost the impact, and the international visibility of European research, structuring research and training capacities in vision science around long-term synergistic collaboration among four academic institutions and four internationally reputed companies engaging in complementary fields of vision science.

Dry eye disease (DED) is a multifactorial disease of the ocular surface that results in symptoms of discomfort, visual disturbance, tear alterations, and tear film instability with damage to the ocular surface. The lack of definitive diagnosis and etiology frustrates ophthalmologists and patients. This lack of concurrence in signs and symptoms poses a problem not only for diagnosing the disease but also for assessing its severity and designing clinical trials to evaluate the clinical efficacy of drugs. A consensus seems to have been reached on the need for newer metrics that may better identify the severity and aetiology of the disease. In light of the high prevalence of DED and the vast economic and human resources spent on treatments, new objective, non-invasive diagnostic technology is needed to enhance and predict the benefits of treatment.
We investigated new techniques to assess the ocular surface health and diagnose DED at its early stage and analyze the propensity to develop DED in the future and anticipate its evolution. The consortium worked on developing a new technique to assess tear dynamics and stability. Texture image analysis approaches were considered to evaluate the tear film and to develop an algorithm for the morphometric analysis of meibomian glands. This methodology allowed to study the relationship of gland morphology with gland function, tear film quality and ocular surface integrity. The partners of the consortium worked in close collaboration to acquire knowledge about the effects of environmental stress and lifestyle on the ocular surface, cornea, and tear film and educate the public on prevention, emphasizing the risk factors that raise the propensity to develop DED. Female sex and the presence of any health conditions were identified as statistically significant risk factors of dry eye disease. Prevalence rates of dry eye disease differed with disease definition/diagnoses.

The consortium addressed different clinical studies to investigate the changes in tear film metrics and ocular signs induced by different types of refractive correction (contact lenses, refractive surgery…). We found that contact lenses may induce measures changes (osmolarity and tear breakup time) in presbyopic population, however, tear meniscus area and vital staining were maintained at the baseline level over the first day and the whole month of contact lens wear. Additionally, patients of ophthalmic surgery are at risk of sub-optimal post-operative refractive and visual outcomes due to DED, which could potentially impact the satisfaction with outcomes and reduce the quality of life (e.g. eye discomfort, lack of independence, depression, etc.). The inclusion of an evidence-based diagnostic test battery, such as that proposed in the recent TFOS DEWS II, was found useful in determining not only the impact of the ophthalmic procedures over the ocular surface but also to appreciate which are the most interesting measures to include in a “real-world” clinical setting such as an eye hospital. It was found that the development of less-invasive surgical procedures to correct a refractive error such as myopia, hyperopia, astigmatism and presbyopia or to reduce the dependence on topical drugs in controlling intraocular pressure in glaucoma patients should begin with an assessment for the ocular surface.

EDEN developed new artificial tear formulations including liposomes, bioadhesive polymers, in-situ gelling polymers or their combinations; as well as other components such as antioxidants, osmoprotectants, and immunomodulators. The conclusion of this study is that all of the ophthalmic formulations demonstrated suitable properties for topical ophthalmic administration. The rheological data suggested that the formulations incorporating gellan gum behave as in situ gelling systems, could provide extended ocular residence time after topical administration in DED treatment. Furthermore, we found that the artificial tears are well tolerated in rabbits. As an important result of the project an in-vitro animal model for dry eye to evaluate novel pharmaceutical approaches to DED management was developed.

Although project did not result in patented products, those are possible as a long term aim based on future collaboration between the consortium partners. In fact, some companies have already shown interest in some of our developments. For example, a multinational company is interested in implementing a diagnostic device with the algorithm for the morphometric analysis of meibomian glands developed under the EDEN framework. Each ESR has published at least one paper in an international peer review journal with impact factor and presented several communications in international meetings. The whole project resulted in 21 papers (being an average 2 papers per fellow) with 26 participations from EDEN fellows (some papers included participation from various fellows) in international peer review journals.
The fellows participated in around 30 outreach events (being an average 3 activities per ESR) ; including Open Research Days, Marie Curie Association meetings, meeting with other EU ITN project´s fellows, to mention a few. A communicative website ( was prepared, where more 50 news have been published, being updated on monthly bases by the fellows. The ESRs have also prepared a promotional video, where they talked about themselves, their experience and work in the project. The video is available in the You Tube channel.
The project contributed to impacts outlined in the proposal. The impact of the scientific advances such as contribution to understanding the processes involved in DED development, improving therapeutic solutions, or respective diagnostic tools, and contribution to the development treatments specific to its various aetiologies has significantly increased the general knowledge about the eye disease.

The students were trained in research and complementary skills. The impact on the ESR's career is already visible as 5 of the students, which constitutes 50% of the EDEN fellows, already have established themselves in professional positions. 3 of them are working at EDEN partner’s institutions and 2 have found employment based on contacts they made whilst working within EDEN.