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ENvironmental COnditions in GLAucoma Patients

Periodic Reporting for period 1 - ENCOGLAP (ENvironmental COnditions in GLAucoma Patients)

Reporting period: 2017-06-01 to 2019-05-31

• What is the problem/issue being addressed? Why is it important for society?
The use of topical eye drops is the most common treatment for glaucoma. However, these eye drops can enhance Dry Eye Disease (DED), which can cause non-adherence to the treatment, leading to loss in vision. It is also known that environmental conditions to which the patient is exposed to may play an important role. It is therefore possible that patients with glaucoma exposed to adverse conditions present a higher risk of non-adherence to treatment.
DED has generally been overlooked in glaucoma patients as clinicians are focused on treating the disease. Reducing ocular surface problems should improve adherence to treatment with better prognosis. In this project we evaluated the ocular surface characteristics of participants with glaucoma and healthy eyes using not only clinically accepted tests but also other promising new technologies to assess DED.

The main objectives of the study were:
• To assess the possibility of using new tests such as ocular thermography to study the ocular surface in glaucoma and healthy participants.
• To assess the effect of the environmental stress on the ocular surface of glaucoma and healthy participants. To examine the ocular surface in glaucoma and healthy participants subjects using clinically established objective and subjective tests.

To address the above, ocular surface signs and symptoms related to DED were evaluated under comfortable environmental conditions, before and after being exposed to controlled environmental stress.

The data obtained show a clear difference in the ocular surface characteristics between glaucoma and healthy participants. The results of the first ENCOGLAP paper showed that just after opening the eye, the ocular surface of glaucoma subjects is cooler. In addition, after a blink, when the participants keep their eyes open, the temperature decreases faster in glaucoma compared to healthy subjects. This may be explained by a decrease in perfusion pressure and it also seems to be related to tear instability, which is likely induced by the use of glaucoma eye drops.
We also found that although the baseline measurements (under conformable environmental conditions) showed more DED signs in the glaucoma group, the exposure to low humidity produced a quite similar effect in both groups in terms of clinical tests. However, the dynamical thermal parameters evaluated (cooling rate and thermal entropy) were affected by the environmental stress only in the control group. In addition, the study showed that the exposure to low humidity increases ocular discomfort, which may increase the risk of low adherence to glaucoma treatment.
In addition, we performed a parallel study that is also related to this project, in the sense that it includes the evaluation of the ocular surface using new technologies. As telemedicine is becoming popular and many clinicians use mobile phone to collect images of different eye conditions, we compared the objective evaluation using machine learning with the subjective evaluation performed by clinicians of images of ocular redness taken with three different mobile phones. The results showed that, if the images are not going to be evaluated by a clinician, the cameras of the phones must be calibrated to obtain reliable results.
Development of the ENCOGLAP project and overview of results:

During the first months the study protocol was finalized, and Ethical approval was obtained. Dr García-Porta also learnt new clinical skills and how to operate the controlled environmental chamber (CEC). Then, from October 2017 until March 2019 we recruited participants and collected data for this project, which included 56 participants. In parallel, appropriate tests for statistical analysis were established and once the data collection was done, statistical analysis was carried out. Preliminary data was presented in several conferences, symposia and workshops

Dissemination and outreach activities were key elements of this project from the beginning. Concerning dissemination, we published the results of the project in peer reviewed high-impact journals, and we presented preliminary results in several top-level international conferences. Examples of the first include a paper published in JOSA A (https://doi.org/10.1364/JOSAA.36.001015) in which we used ocular thermography to evaluate dynamical thermal changes in glaucoma and healthy subjects, funding that the baseline ocular surface temperature is lower and the cooling rate faster in glaucoma. Another paper was published in Scientific Reports (doi: 10.1038/s41598-018-37925-5) in which we compared the objective (automatically) and subjective (clinicians) quantification of conjunctival redness in images obtained with different smart phones, funding that the clinician's evaluation was not affected by different cameras but calibration of smartphone's cameras is essential when extracting objective data from images. An example of a relevant conference in which ENCOGLAP results were presented is that of the American Academy of Optometry 2018 (San Antonio, USA), where a poster showing the effect of environmental stress over the ocular surface in glaucoma and healthy subjects was presented. Another example was a talk about ocular surface damage in glaucoma patients in the International Workshop on the Impact of Auditory and Visual Impairment, which took place in the Southern University of Science and Technology in Shenzhen (China) in December 2017.
As far as outreach is concerned, we focused on different strategic areas. For instance, we gave talks in secondary schools in Spain, participated in the European Researcher’s night 2018 at the Natural History Museum in London, and used social media like Twitter (@encoglap) and Facebbok (@ENGOGLAP.VERU) to connect with the general public. In addition, a webpage of the project was created (https://sites.google.com/view/encoglap) to show news related with ENCOGLAP.
Regarding the impact of this grant on the Research career of Dr Garcia-Porta, we would like to highlight that this grant helped to improve her CV substantially. As a result, she secured a permanent position as a lecturer at ARU.
This project has informed clinicians on factors that influence non-adherence in patients with glaucoma, especially in those who are exposed to environmental stress. This will improve their knowledge of ocular surface problems when prescribing the glaucoma treatment. The project has two clear benefits: 1) Decrease the risk of blindness in glaucoma patients with improved adherence to treatment; 2) Improve the quality of life of the glaucoma patients.
Furthermore, we showed that ocular thermography, an objective and non-invasive technique, is a reliable technique to evaluate DED in people with glaucoma. Our results showed that there are differences in dynamical thermal behavior in the vascular zones between control and glaucoma subjects, demonstrating the potential use of this technique in other ocular diseases.
Images collected with the thermal camera to evaluate the ocular surface temperature after blinking